US Treatment of Reach-Through Claims and Reach-Through Royalties

Frank P. Grassler

 

Preface

 

Genomic patenting poses many questions and problems, one of them being the issues raised by patent claims in the specialized area of reach-through claims, and another one being the issues raised by whether an infringed patent is entitled to an award based on reach-through royalties on sales of products invented by others. This paper will discuss these two distinct subjects, beginning with the subject of reach-through claims.

 

1                    Reach-Through Claims

 

1.00     Reach-Through Claims in General

 

Reach-through claims (sometimes loosely referred to as reach-through patents) are at once a special subset of both genomic patents and research tool patents. Inventors, investors and managers typically take the view that they want to get reach-through claims on their inventions, particularly when a nucleotide sequence is potentially useful in drug discovery technologies. The goal would be to have a claim that takes a novel nucleotide sequence and have that claim ultimately cover or read on an as-yet undiscovered drug that to some extent came about as a result of using the expression product of the nucleotide sequence.

 

The term “reach-through claim” however, is actually almost a pejorative term, since it defines claims that tend to have two fundamental and important flaws. These flaws are inherent in this claiming style since the object of such a claim is to reach through the boundary, or metes and bounds, of the claim to cover products that will be invented by someone else, even though it is well settled that the claim must have understandable bounds so that the public can know with certainty what is part of the invention and what is not. To put it another way, the claim, to be valid, must not reach through (beyond both literal infringement analysis and doctrine of equivalents analysis) to that which is not part of the present invention and is invented by another. This is not to say that a broad claim to a pioneering art cannot read on improvements or that generic claims cannot read on undisclosed embodiments-clearly it has always been the case that they can. But where the fundamental requirements of utility, enablement, description and to a lesser extent obviousness are not met in a way that results in the claim extending its coverage through its legitimate bounds onto to the inventions of others, the claim is not permissible and is said to reach through.

 

We will first set out some illustrative claim types that are typically seen in connection with reach through problems. We will then examine the requirements in the US of description and enablement below, but first review the requirements for utility, since that is a threshold to further examination of a claim.

 

1.01     Representative Claim Types

 

1.02          The Receptor/Small Molecule per se Claim

 

Here the molecule is defined as binding to a target (which may or may not be a receptor, but can include other classes such as enzymes) but the molecule is not yet specifically identified (for example “A receptor X agonist”, where X is a defined biological receptor protein). Here, although the receptor has been identified, the complete list of those ligands (we will use the terms ligand, agonist, antagonist and compound interchangeably here) that bind to the identified receptor is not comprehensively listed in the specification. The specification may disclose one, several, or a relatively great number of ligands, but not all those that the inventor regards as part of the invention. In general, the specifications of such applications reveal little real drug discovery, especially when contrasted with the scope of drug discovery efforts that go on in chemistry-based vertically integrated pharmaceutical companies. The specifications typically mention compound classes in a generic way e.g. triptans, imidazoles, etc., but provide relatively little or no information regarding specific compounds that actually are shown to modulate the receptor in question or that had a reasonable expectation of success in modulating the receptor if one were to follow the teaching of the specification. As anyone who has had experience in prosecuting organic medicinal patent applications knows, a sufficient number of compounds in any given class has to be given that will demonstrate the importance of a core structure or scaffold in predictably modulating the receptor in question.

Additionally, one frequently sees claims similar to this in structure, except that what is being claimed is a monoclonal antibody that will recognize and bind to the defined receptor.

 

1.03          The Method of Screening Claim

 

Here the molecule is defined as having been shown to interact positively with a defined receptor in an analytical screening arrangement (for example, “A method of identifying an agonist of a defined target comprising contacting a candidate agonist with said target under defined experimental conditions”). Here again, although the receptor has been identified and an experimental or analytical apparatus or set-up has been disclosed, the complete list of those claimed ligands that bind to the identified receptor is not comprehensively listed in the specification. A typical claim that depends from this type of method claim is to any ligand identified by this method.

 

1.04          The Functional Use Claim

 

The claim here is to a method of treating a disease by a compound defined not by its structure or structural formula but rather by (a) its ability to bind to a target (for example “A method of treating disease [Y] by administering a compound which is a receptor [X] agonist.”) or (b) by its ability to bring about a biological response of interest (“A method of inducing plasma levels of a secreted protein by administering a compound which is a receptor [X] agonist.”) or even (c) by virtue of having been identified by the method claim as illustrated above. These are somewhat hybrids of the first type of reach-through claim and suffer from the same deficiencies.

 

2        35 U.S.C. §101 and §112, ¶ 1-Utility

 

2.00          US Patent Office Definitions of Specific, Substantial and Credible Utility

 

            The United States Patent and Trademark Office (USPTO) has issued guidelines that set forth the U.S. patentability requirements of “utility” and “written description”[1] The Guidelines represent the USPTO’s current understanding of the statutory requirements of utility and written description.

 

2.01          Credible Utility

 

Where an applicant has specifically asserted that an invention has a particular utility, that assertion cannot simply be dismissed by a USPTO Examiner as being “wrong”. Rather, the Examiner must determine if the assertion of utility is credible (i.e., whether the assertion of utility is believable to a person of ordinary skill in the art based on the totality of evidence and reasoning provided in the application). An assertion is deemed to be credible unless (A) the logic underlying the assertion is seriously flawed, or (B) the facts upon which the assertion is based are inconsistent with the logic underlying the assertion. Credibility as used in this context refers to the reliability of the statement based on the logic and facts that are offered by the applicant to support the assertion of utility. A credible utility is assessed from the standpoint of whether a person of ordinary skill in the art would accept that the recited or disclosed invention is currently available for such use. For example, no perpetual motion machines would be considered to be currently available. However, nucleic acids could be used as probes, chromosome markers, or forensic or diagnostic markers. Therefore, the credibility of such an assertion would not be questioned, although such a use might fail the specific and substantial tests that are explained further below.

 

2.02          Specific Utility

 

 A utility next has to be specific to the subject matter claimed. This contrasts with a general utility that would be applicable to the broad class of the invention. For example, a claim to a polynucleotide whose use is disclosed simply as a “gene probe” or “chromosome marker” would not be considered to be specific in the absence of a disclosure of a specific DNA target. Similarly, a general statement of diagnostic utility, such as diagnosing an unspecified disease, would ordinarily be insufficient absent a disclosure of what condition can be diagnosed.

 

2.03          Substantial Utility

 

 A utility must define a “real world” use. Utilities that require or constitute carrying out further research to identify or reasonably confirm a “real world” context of use are not substantial utilities. For example, both a therapeutic method of treating a known or newly discovered disease and an assay method for identifying compounds that themselves have a “substantial utility” define a “real world” context of use. An assay that measures the presence of a material which has a stated correlation to a predisposition to the onset of a particular disease condition would also define a “real world” context of use in identifying potential candidates for preventive measures or further monitoring. Conversely, here are some examples of situations that require or constitute carrying out further research to identify or reasonably confirm a “real world” context of use and, therefore, do not define “substantial utilities”.

 

A. Basic research such as studying the properties of the claimed product itself or the mechanisms in which the material is involved.

 

B. A method of treating an unspecified disease or condition. (Note, this is in contrast to the general rule that treatments of specific diseases or conditions meet the criteria of 35 U.S.C. § 101.)

 

C. A method of assaying for or identifying a material that itself has no “specific and/or substantial utility”.

 

D. A method of making a material that itself has no specific, substantial and credible utility.

 

E. A claim to an intermediate product for use in making a final product that has no specific, substantial and credible utility.

 

       Note that “throw away” utilities do not meet the tests for a specific or substantial utility. For example, using transgenic mice as food for animals that feed on mice is a utility that is neither specific (all mice could function as such food) nor credible (spending thousands of dollars to genetically engineer a transgenic mouse and then using it as food is not a “real world” context of use; foolhardiness, though common enough in the world, is not “real world”). Similarly, use of any protein as an animal food supplement or a shampoo ingredient are “throw away” utilities that would not pass muster as specific or substantial utilities under 35 U.S.C. §101. This analysis should, of course, be tempered by consideration of the context and nature of the invention. For example, if a transgenic mouse was generated with the specific provision of an enhanced nutrient profile, and disclosed for use as an animal food, then the test for specific and substantial asserted utility would be considered to be met.

 

2.04     Well established Utility

 

There may exist a specific, substantial, and credible utility which is well known, immediately apparent, or implied by the specification’s disclosure of the properties of a material, alone or taken with the knowledge of one skilled in the art. "Well established utility" does not encompass any "throw away" utility that one can dream up for an invention or a nonspecific utility that would apply to virtually every member of a general class of materials, such as proteins or DNA. If this were the case, any product or apparatus, including perpetual motion machines, would have a "well established utility" as landfill, an amusement device, a toy, or a paper weight; any carbon containing molecule would have a "well established utility" as a fuel since it can be burned; and any protein would have well established utility as a protein supplement for animal food. This is not the intention of the statute.

 

2.05     Utility and US Courts

One must bear in mind that the Court of Appeals for the Federal Circuit (CAFC), which is under no obligation to follow the PTO Guidelines, may not ultimately agree with the restrictive scope of the PTO’s recent Utility Guidelines. Although the CAFC supports the USPTO’s interpretation of the relationship between §101 and §112[2], the  CAFC has on the other hand tended to consider utility a very low threshold barrrier to patentability. See, for example the 1994 case of In re Alappat, [3]  where an algorithm that merely produced smooth waveforms was found to have the requisite usefulness.  The CAFC has gone so far as to say that a claimed invention must be totally inoperative to lack credible utility[4], and declared a willingness to accept in vitro evidence or data as establishing, for example pharmacological utility in the absence of clinical studies[5].

 

In drafting patent applications, in the field of biotechnology where a reach- through claim is most likely to be found, applicants should take note of the relatively favorable decision of the CAFC and take care to formulate some sort of practical utility within the specification, and if possible to tie that practical utility to plausible mechanisms of actions since after all: “Obviously, if a claimed invention does not have utility, the specification cannot enable one to use it.”[6]

 

3        35 U.S.C. §112, 1st Paragraph, Written Description

 

3.01     Description in General

The first key flaw that makes a claim impermissibly reach through is that the specification does not reasonably convey to the person of ordinary skill in the art a description of the completed invention, in the sense that the person of ordinary skill is not left convinced that the applicant was actually in possession of the claimed invention as of the date of filing the application.

 

            In general, the rule is that if the specification conveys with reasonable clarity that the inventor was in possession of the invention as claimed as of the effective priority date, then there is adequate written description.[7] The criteria by which a claim will be examined in the USPTO are based on a line of cases, the most important of which is The Regents of the University of California v. Eli Lilly & Co.[8]  This case, which was decided in 1997 and which forms the basis for the Utility Guidelines issued by the USPTO, was directed to the issue of adequate written description for generic claims for nucleic acids when only a single species was disclosed in the specification. The case also addressed the issue of adequate written description for a species that was not disclosed, but which was related to the disclosed species. In this case, the three claims at issue were directed to cDNA encoding mammalian insulin, vertebrate insulin, and human insulin, while the disclosure was limited to an amino acid sequence for human insulin and a cDNA sequence for rat insulin.  There was no disclosure of any other mammalian insulin species at the cDNA level.

 

The CAFC drew a distinction between obviousness and adequate written description. It cited case law holding that the claimed invention may, in fact, have been non-obvious but still was not adequately described.[9]  Further the Court stated that a claim may be enabled, but still may not be adequately described. Therefore, it is clear that a claim can be both non-obvious and fully enabled and still not be adequately described.

 

Based on a line of cases the CAFC cited in the Lilly opinion, the test for adequate written description is whether the specification conveyed the claimed invention with reasonable clarity so that the person of ordinary skill in the art would have known from the disclosure that the applicant was in possession of the claimed invention. Evidence of such possession can take the form of actual reduction to practice, clear depiction in detailed drawings or structural chemical formulas, or through written description describing sufficient relevant identifying characteristics. Any of this can be shown by words, structures, figures, diagrams and formulas, but not by merely describing or arguing those features which may make the claimed invention non-obvious or those technical details which may even enable the invention. The Court stated that an adequate description of a DNA such as a cDNA, would require a precise definition such as by structure, formula, chemical name or physical properties, but not by a mere wish or plan for obtaining the chemical invention (viewing, as the Court did, the claimed nucleotide sequences as being chemical compounds).

 

In this regard, the Court relied on the case of Fiers v. Revel,[10] in which an inventor had shown a method that may in fact have been effective to produce the DNA sequence, but was not sufficient to support a claim to “ a DNA sequence encoding protein X” because it did not disclose the sequence itself. The Court made it clear that a name such as “cDNA” is not sufficient and that the applicant had provided no distinguishing information regarding the identity of the DNA, no sequence information and no relevant structural or physical characteristic.

 

Since the Lilly Court used this rationale where a nucleotide sequence is concerned and stated that only the sequence per se is sufficient to describe a claim to the sequence, one could argue that Lilly might be limited to DNA sequences. On the other hand, it is clear that the Court applied principles from the law of the chemical art by treating DNA as a chemical entity, making it critical that the DNA be characterized by its sequence and nothing less, and meaning that Lilly in all likelihood will not be limited to claims to DNA sequences.

 

The Court stated the following, “ A written description of an invention involving a chemical genus, like a description of a chemical species, requires a precise definition, such as by structure, formula or chemical name of the claimed subject matter sufficient to distinguish it from other materials” (citing Fiers). Therefore, to obtain a claim to any chemical compound, including a nucleotide sequence, that compound must also be described in detail in the specification in order to meet the written description requirement.

 

The Court also said that with respect to the claims to vertebrate or mammalian insulin, the claims did not distinguish the claimed genus from other genuses except by function and there was no definition of any structural features commonly possessed by members of the claimed genus that would adequately distinguish them from other genuses. The Court said that a definition by function does not suffice to define the genus because a function is only an indication of what the gene does rather than what the gene is. 

 

Therefore at the USPTO, following this case and its predecessor cases, the focus is on the following standards in the Utility Guidelines:

 

(1)   Description of structure of a representative number of claimed compounds; and

 

(2)   Description of chemical or physical characterization of a representative number of claimed compounds or of the function of a representative number of claimed compounds (other than binding to the protein at issue).

 

3.02     Written Description of Compounds

 

Reach-through claims, directed either to compounds per se that modulate the novel receptor or to compounds identified by screening procedures against the novel receptor, generally are not limited to specific species or to specific classes of compounds, much less to specific structures. The claimed compounds may be, and generally cover, a large and diverse group of molecules. These typically end up including many thousands of large or small organic (we will follow an industry convention that considers small molecules to be organic molecules having a molecular of 500 of less) and inorganic molecules, antisense nucleic acids, fragments of nucleic acids, peptides, ribozymes, antibodies and the like, without actually disclosing core structures or representative numbers of core structures or functions for any of them. Also typically, the specification may disclose no modulator other than the single ligand of the example, which may often be the natural ligand. Alternatively the specification may disclose additional modulators but not have provided a sufficient number of modulators such that a core structure (for example a Markush group) can be defined for one or more classes of modulator.

 

In this situation the USPTO would properly take the position that the claims are not likely to comply with the written description requirement, citing Lilly and In re Ruschig. [11] However, where the specification does describe the structure of a representative number of compounds that would provide a core structure, a claim could potentially be obtained directed to compounds of this class. The USPTO would have to be convinced that possession of the core structure is reasonably predictive of the ability to modulate the receptor. To accomplish this is in actuality an exercise in drafting a specification that, with respect to the ligands desired to be validly covered by the claim, is as detailed as the description would be in the situation where the applicant is claiming the compounds per se in a conventional case, for example an organic medicinal chemistry genus and species case. In other words, if you want a genus of compounds (that interacts with your receptor) to be considered to be correctly described, look to how it was done in a chemistry case. A detailed discussion of how to meet the description requirements in chemical patent practice is beyond the scope of this paper, but one can readily grasp the scope of what is considered to be adequate description of a given genus by a study of issued patents in the area. If you think di-substituted imidazoles block your receptor to induce vasoconstriction particularly well, you should study some issued patents in that art. A claim well-drafted in this manner will be much less likely to reach through and be rejected on that basis.

 

Would the CAFC likely uphold the USPTO’s application of Lilly to those situations in which claims cover compounds per se that are ligands to a novel receptor, or cover compounds identified by screening methods against the novel receptor, but the compounds have not been disclosed as to specific formula, structure, or function, but rather by generic class, such as organic molecule, inorganic molecule, ribozyme, and so forth? Since the decision in Lilly was based on a rationale derived from the written description requirement as applied in the chemical art, it appears likely that the Court would apply the same standards, which it applied in assessing adequate written description for the terms “vertebrate DNA” or “mammalian DNA”. That is, without a specific structure(s), the disclosure would not be found to adequately describe such a generic claim. With respect to the claiming of compounds identified by screening, it could be argued that such a claim would also be unlikely to meet the requirements set forth in Lilly for a generic claim unless screening conferred or resulted in some identifiable generic structural limitation. At the very least, the applicant would have to show that screening produced a representative number of compounds, the term “representative” being based on some type of common physical or chemical characteristic that would convey to the person of ordinary skill with reasonable clarity that the inventor actually was in possession of a particular genus of compound.

 

US Patent Number 6,083,705 is an example of a claim drafting strategy attempting to get around this problem, in which the claims are essentially drawn to compounds identified by screening via couching this limitation as a process limitation and tacking it onto the end of a screening claim. Screening claim 3 is as follows:

 

“3.        A process for determining whether a chemical compound is a human α1c adrenergic receptor agonist which comprises contacting cells transfected with and expressing DNA encoding the α1c adrenergic receptor with the compound under conditions permitting the activation of the α1c adrenergic receptor, and detecting an increase in α1c adrenergic receptor activity, so as to thereby determine whether the compound is an α1c adrenergic receptor agonist.”

 

The following dependent claim 31 was then submitted in an attempt to protect the compounds identified by the method in the preceding claim:

 

“31.      A method of preparing a pharmaceutical composition which comprises determining whether a compound is an α1c adrenergic receptor agonist or antagonist using the method of any of claims 3 through 6 and admixing said compound with a pharmaceutically acceptable carrier.”

 

            The ‘705 patent is primarily directed to a novel receptor. A method of screening claim, a claim otherwise allowable by the USPTO, contains a reach-through process limitation. The method is written as a method for preparing a pharmaceutical composition, which adds a step following the screening steps wherein a compound is identified as an agonist or antagonist and is then mixed with a pharmaceutically carrier. Such a claim could block others from methods of treatment because in a method of treatment, a pharmaceutical composition is needed. The disclosure however, does not contain description of specific compounds or a representative number of compounds, but rather discloses that genus of compounds that is based on the collective ability of the compounds of the genus to be identified by a screening procedure for a compound that modulates or binds to the receptor. Thus, the disclosure is limited to what that compound does and not what that compound is. Accordingly, under Lilly, it can readily be argued that this claim is invalid and reaches through because the compound that is the subject of the claimed limitation is a compound defined not by what it is, but by what it does.

 

The USPTO would allow the screening method for identifying compounds. But, can claim 31 be sufficiently described? If we dissect claim it would appear to comprise the following elements:

A compound identified by screening,

which is admixed with a pharmaceutical carrier.

 

For simplicity, this element of the claim could be broken in two pieces. One piece is “a compound identified by screening against target X.” The other piece is a method for making a pharmaceutical composition “by admixing a compound with a carrier.” Based on properly applied practice of the USPTO as to the compound, neither element of this claim is adequately described in the specification. Since they are two elements, each requiring their own degree of description, one cannot simply get an additive effect by putting the two elements together, which would therefore not seem to be an adequate drafting strategy to overcome the deficiency. Based on the USPTO Guidelines, therefore, this claim should fail for lack of adequate written description since the compounds were not adequately disclosed. And it appears that there is a strong likelihood that the CAFC would adopt the same position because this claim to a method of making a pharmaceutical composition finds its point of novelty only in the compound.

 

3.03     Written Description of Methods

 

The USPTO applies the same rationale to claims to methods of treating a disease by administering a compound identified by the screening procedure. This type of claim can be written more generically so that it is not directed to methods of treating a disease. It can be written as a “method for modulating the target protein by administering a compound under conditions suitable for modulation.” Such a claim (to a method of modulating) could potentially also reach through to methods of treatment, since it is a dominating generic claim.

 

The position of the USPTO is that Lilly extends to such method claims as well. That is, unless compounds have been adequately described, a method for using compounds in the generic sense, either compounds per se or compounds identified by screening, would not be adequately described.

 

The rationale for this position can be illustrated by the following hypothetical claim based on Lilly:

 

“A method for assessing the level of insulin in a mammalian cell by hybridizing a mammalian insulin cDNA to a nucleic acid in said cell and assessing the level of hybridization between said mammalian insulin cDNA and said nucleic acid in said cell. “

 

Since the CAFC takes the position that a genus of compounds, i.e. mammalian insulin, is not adequately described by the disclosure of one insulin species, using the same rationale, this claim should, if issued, be invalid for lacking adequate written description as to the genus “mammalian insulin”. The method, of course, is per se old.

 

U.S. Pat. No. 6,048,850 is an example of an issued method claim that is illustrative.

 

A method for selectively inhibiting PGHS-2 activity in a human host, comprising administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product in a human host in need of such treatment.

 

The disclosure in this patent generally refers to many genuses of compounds including homologs of the gene, analogs of the gene, antisense compounds, ribozymes, antibodies, peptides and small organic and inorganic molecules. However, no specific compounds are identified and the specification does not, therefore, provide a description of the structure of a representative number of claimed compounds or a description of the chemical or physical characterization of a representative number of claimed compounds (for example IR or NMR characterizing data) or the function of these claimed compounds, other than by generically stating that they would modulate the involved protein. Based on the current position of the USPTO, this claim would fail to meet the written description requirement for these non-steroidal compounds, following the rationale in Lilly.


 

4     35 U.S.C. §112, 1st Paragraph, Enablement

 

4.01     Enablement in General

 

The second key flaw that makes a claim impermissibly reach through arises when the specification has been drafted in such a way that a person of ordinary skill in the art cannot make and/or use a reasonable number of claimed embodiments of the invention, i.e. across its claimed scope, unless that person has to apply an undue amount of experimentation, which is a requirement of the statute.

 

In general, the USPTO applies the factors set forth in In re Wands. [12]  The claim at issue there was directed to a method for detecting Hepatitis B surface antigen by using ultra-high affinity monoclonal antibodies. Representative is claim 7.

 

“7.        Monoclonal high-affinity IgM antibodies immunoreactive with HbsAg determinants wherein said antibodies are coupled to an insoluble solid phase, and wherein the binding affinity constant of said antibodies for said HbsAg determinants is at least 109M-1 “.

 

The CAFC indicated that the determination of what constitutes undue experimentation in a given case requires the application of a standard of reasonableness, having due regard for the nature of the invention and the state of the art as of the time of filing the application. It indicated that the test is not merely quantitative, since a considerable amount of experimentation is permissible if that is what is routine in the industry or if the specification provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed. It cited the factors from Ex parte Forman, [13] including: (1) the quantity of experimentation necessary in that art, field or industry, (2) the amount of direction or guidance presented by the specification, (3) the presence or absence of working examples in the specification, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those of ordinary skill in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.

 

Applying these factors, the Court in Wands found that a considerable quantity of experimentation was necessary, but no more than that which was reasonably to be expected in that particular art or in that particular industry. The specification described how to make a hybridoma and screen the hybridoma for antibodies of a particular defined affinity. The Court described the nature of the invention as the development of monoclonal antibodies, involving screening hybridomas to find an antibody with a desired characteristic. It described the level of skill in the art as high. It also described that art as reasonably predictable, based on the fact that such antibodies had been for some time obtained against other antigens and there was no reason to believe that raising antibodies against the hepatitis antigen would be an exceptional case. The examples showed that there was a reasonable rate of success in obtaining the claimed high affinity antibodies.

 

Somewhat at the opposite end of the spectrum of allowability, are screening claims where the receptor is an orphan and no known way exists of activating the receptor and accordingly, providing a screening assay that can be made and used without more teaching.

 

4.02     Enablement of Compounds

 

The USPTO has taken the position that the scope of receptor-ligand claims directed to compounds that are enabled by the specification depends on the compounds themselves that are in the specification. Receptor-ligand claims can generally be obtained for the specific compounds disclosed. The position taken by the USPTO in the most extreme case, that is, where only the original single ligand is disclosed, is that the claims are not enabled across their entire scope. The reasoning goes that such claims encompass a genus of compounds defined only by their function (interaction with the receptor), and the relationship between the structural features of members of the genus and their function has not been defined. Therefore, in the absence of such a relationship that it is either disclosed or would have been recognized, based on information generally available to those of skill in the art, the person of ordinary skill in the art would not know how to make and thus how to use compounds that lack such structural definition. The USPTO takes the position that this deficiency cannot be overcome merely because the person of ordinary skill could assay a compound of interest “since one would have no knowledge beforehand as to whether or not any given compound (other than those that might be particularly disclosed in an application) would fall within the scope of what is claimed.”[14] Accordingly, the USPTO concludes that it would require an undue burden of experimentation to screen undefined compounds randomly for the claimed activity.

 

How might a court approach this question? A specific question is whether the term “make”, with respect to compounds, necessarily requires something more than synthesis (either in vitro or in vivo). It could be argued, for purposes of enablement, that given the large number of compounds available, “identification” of a compound meets the “how to make” requirement of section 112, first paragraph.  “Make” could be equated conceptually with “obtain” and, therefore, could be fulfilled by the availability of such a large number of potential screenable compounds.

 

If a court were to adopt such an interpretation, the question would then become how the Forman factors apply. That is, what type of experimentation would be required to screen random compounds or classes of compounds to find a hit. It could be argued that the drug screening art is sufficiently developed to enable a reasonable rate of return for compound identification. There is a diversity of compounds that exists in the art and, if a court found the combinatorial library technology of sufficient maturity to generate a diversity of compounds, the court might find such claims to be enabled by virtue of the very existence of the sheer total number of compounds. In the case of compounds identified by screening, what is the success rate likely to be for obtaining compounds that would serve as antagonists, agonists, or otherwise modulate a target?

 

The success rate in screening not only combinatorial libraries but also a diversity of compounds available to the person of ordinary skill in the art anecdotally appear to be on the order of from between 0.1-1.0% from screening approximately 1 x 105 small molecule compounds, with success rates appearing to be smaller for peptides. Accordingly, based on the maturity of the art of compound screening and the level of return, it is possible based on the fact scenario in Wands that such claims could be enabled. Applying the Wands factor to this case, we can conclude that (1) although a high quantity of experimentation is required, this is expected in the industry; (2) screening of compounds that modulate targets has been reasonably successful in the industry; (3) the level of skill in the art is high; (4) the target is not one that would be subject to any particular drawbacks that would distinguish it from any of the other targets for which modulators have been found by screening; (5) the specification directs the person of ordinary skill in the art to screening processes if such were not already routine in the art. Certainly, working examples would help. Extrinsic information could be presented to show that for a given class of compound, a reasonable success rate could be predicted.

 

However, this would only be a reasonable success rate for the category of compounds that the pharmaceutical industry characterizes as “hits” Such compounds are only in the rarest circumstances able to be progressed through the rest of the new drug product development pipeline to become a marketed drug someday. Instead the “hit” compound (or, as is more typically the case, several hits produced by a high throughput screen exercise) is studied by organic medicinal chemists and pharmacologists as to how the compound can be made more “drug-like”. Being “drug-like” involves factors such as aqueous solubility, ability to cross the lining of the gastrointestinal tract, potential for inducing a given metabolic enzyme level, and so forth.  An otherwise promising hit may be as soluble as a brick. So modification chemistry is undertaken to produce homologs, analogs and close congeners. This involves extensive chemical modification work around the structural formula of the “hit” until a molecule with more desireable properties results, which is categorized as a “lead”. The “lead” is progressed and may or may not get past efficacy and toxicity indicators. The “lead” is what is most sought after in terms of one or more allowed compound-per-se patent claims. The point here is that a lot of organic medicinal synthesis has to take place, with only a limited amount of predictability about the outcome of optimizing the hit to produce a lead. Should the imidazole hit be alkylated at the 4 position? Should it be acylated? Should the alkyl substituent be aminated and the amine in turn be mono- or di-substituted? The permutations quickly become very large numbers. Is there any teaching on any of this in the specification? The less teaching there is, the less likely it is that the claim to a receptor and a genus of ligands is enabled across its breadth and it therefore reaches through.

 

4.03     Drug Screening and Raising Monoclonal Antibodies

 

In general, the position of the USPTO is that this type of claim (i.e. “A monoclonal antibody which recognizes the receptor having the sequence which consists of  SEQ. ID No:X…”) is patentable even if specific antibodies are not disclosed. This position may have the blessing of the CAFC under the case of Enzo Biochem, Inc. v.  Gen-Probe Inc.[15] This case was directed to the issue of written description. The patent claimed nucleic acid probes that selectively hybridize to genetic material of bacteria that cause gonorrhea. The CAFC, which affirmed a decision from the Board of Appeals, discussed why written description for the claimed invention was inadequate. The CAFC found that the patentee had provided only vague details about the nucleotide sequences, and did not identify chemical structures of probes. However, of benefit to future application drafters, the CAFC cited the Written Description Guidelines as stating that an applicant could show that an invention was complete by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure. The CAFC also directed readers of the opinion to the Written Description Guidelines in order to learn how to comply with the written description requirement for a claim directed to an isolated antibody capable of binding to antigen X “considering, ‘the well defined structural characteristics for the five classes of antibody, the functional characteristics of antibody binding, and the fact that the antibody technology is well developed and mature’”.

 

Note that the name “antibody” can be said to describe a chemical entity. The claim simply calls for the antibody binding to the antigen, This could be construed as a chemical entity defined by its function and not its structure. The USPTO appears to have made an exception for antibodies because the art of raising antibodies is now so well-developed. In point of fact, the structure of an antibody to which the Court refers is a generic one and the ability to bind is a characteristic that can not be predicted in advance for any given antibody for a given antigen. The drug screening process could be analogized to antibody production. The antibody is not made directly from the target protein. It is a preexisting molecule circulating in the body. The target protein is needed to select the cell that produces the antibody. The produced antibody is then identified by means of the target protein. Moreover, a myriad of different antibodies can be raised against a specific antigen. It would be impossible to even disclose all of them, or to provide a ”core” structure for specificity. In the same way, the target protein is needed to bind or otherwise biologically interact with a compound in a biological assay. That is how the compound is selected among the many possible compounds. The question may come down to one of reasonable predictability, ie., the USPTO does not consider the screening process to reach the level of predictability that exists in the antibody art.

 

4.04     Enablement in Pioneering Inventions

 

In closing the discussion on enablement it is worthwhile noting that the CAFC has recently held in the case of Plant Genetic Sys., N.V. v. DeKalb Genetics Corp.,[16] that no special consideration is given to an invention that can be characterized as a pioneering invention in this regard, and such an invention will not be entitled to a lower standard of enablement under 35 U.S.C. § 112, first paragraph. Some practitioners may recall previous cases of the CAFC and its predecessor court, the Court of Customs and Patent Appeals, that suggest that lower standards of the rules of patentability should be accorded to pioneering inventions, but the Plant Genetics opinion characterizes those passages as dicta and not case law.

 

5          Obviousness

 

A brief word is also in order about how obviousness can create reach-through claims. A broad claim drawn to any and all ligands that bind to a newly claimed receptor will be very hard to obtain in the context of the prior art. This is so since in most instances there will already in the prior art have been at least one drug to treat the disease and which inherently acted through the receptor, even though the mechanism had not been fully understood.  An old principle of pharmaceutical patent law says that discovery of the underlying mechanism of action of an old drug does not entitle the discoverer to a new patent that would dominate the administration of the old drug. This does leave open the possibility though of the discovery of a receptor in the pathophysiology of a disease for which there was no prior drug in use that acted at that receptor. This situation may, all other things being equal, get around the prior art problem, particularly if submitted in the form of a method of screening or an assay claim.

 

6                    Reach-Through Damages

 

Can a patentee ever recover damages for infringement that would include the award of a royalty on the sales of a drug discovered or validated through the unauthorized use of a patented target? This question has occupied the thoughts of inventors, investors, executives and attorneys in the biotech and pharmaceutical sectors for many years now. Thousands of patent applications were filed in a hope that a theory would emerge that would grant such damages, perhaps even trebled for willful infringement. This section examines the rules of US damages law as they would apply to a patentee seeking an award of reach-through damages from a US District Court.

 

 

6.01     General Principles of Damages

 

A court’s authority to award damages arises solely from the Patent Act. 35 U.S.C. § 284 states “Upon finding for the claimant the court shall award the claimant damages adequate to compensate for the infringement, but in no event less than a reasonable royalty for the use made of the invention by the infringer.” The award is not discretionary, it is mandatory if infringement was found. There is no such thing as de minimus  infringement or an infringement so small that no award would be made on that basis (although as a practical matter no rational patentee would engage in the expense of patent litigation where it was known beforehand that the infringement was relatively small). But the damages have to be compensatory, not punitive. The patentee must show that it was actually damaged, and how it was damaged. The court has to ask “had the infringer not infringed, what would the patentee have made?” Aro Manufactoring Co. Inc. v. Convertblel Top Replacement Co. [17]

 

A necessary corollary of this, and one that is very frequently overlooked, is that patent damages cannot be awarded based upon the amount of the infringer’s profit or other gain by reason of the infringement. The Patent Act was amended by Congress in 1946 to eliminate a patentee’s right to recover the infringer’s profits (at common law this was the remedy of disgorgement). Instead, only the patentee’s damages are recoverable which is the actual pecuniary loss as proven by admissible relevant evidence. Since 1946 there has been no hint by any appellate court that an award of damages can be based upon an infringer’s profits.

 

In Rite-Hite Corp. v Kelley Co., Inc., [18] the CAFC affirmed an award of damages based on lost sales of an unpatented product (a vehicle restraint). For this reason, some have thought that the door has opened to an award of damages based upon the infringer’s profits on the theory that if the Rite-Hite Court has made damages recoverable for reasonably foreseeable harm to the patentee, then surely it is foreseeable that an infringer will wrongfully reap a windfall profit that can be at least in part disgorged. The Rite-Hite Court based its decision on the `entire market value rule'. This rule permits recovery of damages for the value of a whole product, even though just a portion of the product is patented, if the patented portion is the basis for customer demand for the whole product. The Rite-Hite Court, however, stated that there was:

 

“…no basis for extending that recovery to include damages for items that are neither competitive with nor function with the patented invention.”

 

6.02     Lost Profits As the Basis Of An Infringement Award

 

Nonetheless, 35 U.S.C § 284 authorizes an award of “damages adequate to compensate for the infringement, but in no event less than a reasonable royalty for the use made of the invention by the infringer.” Damages may firstly be based on lost profits; for instance, lost profits arising from potential sales that were lost to actual sales made by the infringer; lost profits arising from price cuts made because of the infringer's competition; and lost profits arising from projected lost sales. See Lam, Inc. v Johns-Manville Corp.[19] On the other hand, an invention directed to a basic research tool may not fit within the `lost profits' model for damages owing to the limited use of or market for a basic research tool, or the reality that many such patentees do not manufacture and market the tool for sale and therefore cannot be said to be in competition for sales with another party who makes the research tool and uses it but doesn’t sell it.

 

 

What about lost profits based upon sales of drugs discovered, developed, or produced using the patented research tool? Such an award is unlikely for the simple reason that almost always the owner of the research tool patent is not a competitor of the drug company that has developed a drug.  Also, in many cases, the patentee’s research tool was not used in the original discovery of the drug, but was used rather to confirm the drug’s activity or to perform safety profiling, which rules out the ability of the patentee to show that but for the use of the patented research tool, a drug would not have been discovered. (This also sets aside a consideration of the availability of the defense available to drug companies under 35 U.S.C. §271(e)(1), which is the subject of another presentation today).

 

6.03     Reasonable Royalty As The Basis Of An Award

 

Assuming therefore that a patentee is unable to prove lost profits, it nevertheless is entitled to recover damages no less than a reasonable royalty for the use made of the invention. Now it is important to understand that the term ‘reasonable royalty’ is a legal fiction. A reasonable royalty is not the same thing as a running royalty that has been agreed to by two private parties in an actual contract negotiation. Neither is it a reach-through royalty (although it is common to hear arguments that a reach-through royalty should be the reasonable royalty). There are different ways that a court can properly determine what this reasonable royalty should be.

 

If there is an established royalty rate for patented inventions in the applicable field, whether established by the patentee or by the relevant industry, that rate can be deemed to be the best measure of what a reasonable royalty would be. Usually though, an established royalty rate doesn’t exist, so a court must come up with a reasonable royalty by trying to figure out what would have been agreed to in a hypothetical arms-length license negotiation between a willing licensor and a willing licensee at a moment in time just before infringement began. Hanson v. Alpine Valley Ski Area, Inc. [20] See Georgia-Pacific Corp. v United States Plywood Corp[21]; and Railroad Dynamics, Inc. v A. Stucki Co.[22]  The court does this by taking into account the proffered evidence, including the nature of the research tool, the nature of the market, availability of non-infringing alternatives, stacking royalties and other economic factors.[23] What makes the reasonable royalty a hypothetical amount and a legal fiction, is that the judge’s determination of what would have been agreed to in the hypothetical negotiation takes place in a trial after the patent has been found to be valid and after it has been found to be infringed. Therefore, while an actual business manager representing a licensee will try to bring a royalty rate down by arguing the weakness of the patent or by raising potential defenses, in the reasonable royalty determination, those factors cannot be taken into account.

 

The reasonable royalty is a hypothetical amount that a court arrives at after having applied a percentage rate to a base amount (the base amount will be determined from evidence on sales volumes at issue in the relevant market during the relevant time period). The rate comes from subtracting the normal customary net profits on products analogous or similar to the infringing product from the projected net profit from sale of an infringing product (this calculated rate is called the residual rate). That residual multiplied by that base will then produce a residual amount. This is called a residual because it represents the difference in anticipated net profits of two alternative courses of action, namely infringing and not infringing. After calculating the residual, the court can then adjust that amount to a lump sum present value, and it can increase that number due to aggravating circumstances in the case before it (i.e. willful infringement) or it can decrease that number due to mitigating circumstances (i.e. good faith efforts by the infringer to obtain a license prior to the infringement).  For a full and complete explanation of the correct application of this analytical approach to calculating the reasonable royalty, and then using the reasonable royalty to calculate the total damages award, see TWM Mfg. Co. Inc. v. Dura Corp. 231 US.P.Q. 525 (D.D. E.D. Mich. 1985) aff’d en banc 789 F.2d 895, 229 U.S.P.Q. 525 (Fed. Cir. 1986).

 

Now this may seem inapplicable to the situation where the patent is on a receptor used in screening, and the issued claim validly covers the drug at issue. The patentee is not in competition with the drug company, either for sales of the receptor, nor for sales of the drug. The analysis still holds because obtaining the receptor at whatever the price may be, (lump sum, negotiated royalties, etc) is a research expense or cost to the drug maker, and there can still be calculated a residual between anticipated revenue from having infringed by using the receptor to discover the drug (presumably a lower expense and therefore a greater net profit) and anticipated revenue from not having infringed by using some alternative to using the receptor in the drug discovery program (e.g. a whole cell assay, probably resulting in a higher expense and therefore a lower net profit). Again, a residual amount is the result, which can likewise be increased or decreased for aggravating or mitigating circumstances, and which can form part of an overall award that can include enhanced damages for e.g. willful infringement[24] and attorney’s fees in an exceptional case.[25]

 

6.04          Enhanced Damages and Exceptional Cases

 

Since an award of a reasonable royalty, like an award of lost profits, is intended as compensation for infringement, the calculation does not take into account the infringer’s culpability for infringement. Culpability is dealt with by the second paragraph of §284, which separately authorizes the court to award enhanced damages by increasing the award to up to three times the amount of actual damages awarded under the first paragraph of §284. Again, the usual reason behind an award of enhanced damages is that the infringer’s behavior has been found to have been willful, although a showing of willfulness is no guarantee of an award of enhanced damages.

 

It is tempting to conclude that there is a right to a reach-through royalty on sales of a drug discovered at least in part through use of a patented research tool as the measure of the reasonable royalty, especially since the Rite-Hite case where the Court stated that the patent holder is entitled to any damages which are reasonably foreseeable. Surely it is reasonably foreseeable that if you use a patented research tool in a drug discovery program without compensating the patentee, then the patentee is being damaged by virtue of your non-participation in their licensing program. However, in addition to the rule that the infringement award must reflect the actual damages and not disgorge the infringer’s profits, there is additionally an upper limit on what a reasonable royalty can be. The amount of damages awarded as a reasonable royalty cannot exceed an amount that would put the infringer in the position of making less than their ordinary non-infringing profit. This is illustrated by recalling that the residual rate is calculated by subtracting the normal or customary profit from the profit anticipated or realized from use of the infringing product. TWM Mfg. Co. Inc. v. Dura Corp.  For example, if an infringer would have made a dollar of profit on a ten dollar sale in a situation in which there had been no infringement, and they ended up making three dollars of profit on the ten dollar sale since they did infringe, the ordinary damages awarded to the patentee (not including though, any consideration of enhanced damages for willful behavior) cannot leave the infringer with less than the one dollar they would have ordinarily made, and the patentee will get the two dollars, but not the three dollars generated by the infringing act.

 

Additionally there is a six year statute of repose in the US which bars the award of damages for acts of infringement that occurred more than six years prior to the time of filing your court action. 35 U.S.C. § 286. If you combine this with the US rule against an award of speculative damages (see below), you have a situation in which you cannot bring an action for damages since you cannot meaningfully calculate them (no drug has been approved) yet the drug discovery, development and approval process is so long that chances are strong that the infringing activity took place more than six years ago.

 

Where the patented research tool provides a novel means of producing an end product, the argument for reach-through royalties becomes realistic. In Ajinomoto Co. v. Archer-Daniels-Midland Co.,[26] the patent there claimed a method of modifying the genetic structure of bacterial strains to produce amino acids in increased quantities. The patent specifically described a mutation of a gene in E. coli bacteria that controls the synthesis of the amino acid threonine, and subsequent insertion of the modified genetic material into a host bacterial strain modified in order to produce excess quantities of threonine. After finding infringement, the District Court awarded reasonable royalty damages by applying a fixed per unit royalty rate of $1.23 per kilo of threonine produced by the infringer. The District Court arrived at what amounted to a reach-through royalty after concluding that these were the terms the parties would have agreed upon in a hypothetical negotiation conducted just prior to the commencement of infringement. Importantly, the expert witness for both sides testified that the outcome of the hypothetical negotiation would have been a royalty on the infringer’s sales of threonine; they simply differed over the rate. This holding is consistent with the CAFC’s holding in Minco, Inc. v. Combustion Engineering, Inc., [27], upholding the award of a reasonable royalty based upon sales of fused silica produced by a patented rotary furnace.

 

At the other end of the spectrum are research tools used merely to test or confirm the activity of a potential drug product. Such tools may demonstrate the safety of a candidate compound, but they are not the causative agent for discovery of the compound, nor do they play a role in producing the compound. In these circumstances, it is unlikely that hypothetical licensors and licensees would have negotiated a reach-through royalty on each compound tested, and a court therefore in not likely to enter a reasonable royalty award of damages based upon a reach-through royalty attached to sales of the compounds.

 

Somewhere in between these two ends of the spectrum are research tools that facilitate drug discovery. In SIBIA Neurosciences, Inc. v. Cadus Pharmaceutical Corp.,[28] the patent broadly claimed methods of screening compounds to identify those that exhibit agonist or antagonist activity with respect to surface receptors.  The claimed assay involved the use of a recombinant cell having a heterologous cell surface receptor and a reporter gene construct. At trial, the jury returned verdicts finding that assays developed and offered by Cadus infringed  SIBIA’s patent, that the patent was valid, and that SIBIA was entitled to reasonable royalty damages in the amount of $18 million. The damages calculation was based upon a hypothetical license containing a flat fee of $100,000 per molecular target validated for screening against compounds, and a royalty based upon net sales of future drug products discovered in the future. The jury’s award reflected projections by SIBIA’s expert witness both as to the number of successful new drug products likely to result from infringing assays performed by Cadus and its collaborators and as to the future sales of these as yet undiscovered products. Cadus appealed the damages award as well as the validity and infringement findings. Cadus argued that the damages award in the form of a royalty rate had been incorrectly based upon future sales of drugs that might be developed from assays directed to those molecular targets, and that such sales and therefore such royalties were wholly speculative. Unfortunately, the CAFC concluded that the SIBIA patent was obvious and therefore never reached the damages issue. [29]

 

The Cadus appeal in the SIBIA case is a good illustration of some of the problems that arise in trying to calculate reach-through royalties that would have been paid to the patentee for infringement of a research tool patent. At trial SIBIA’s expert estimated: (1) the probability that a molecular target supplied by Cadus would yield a “primary hit” when tested against the compound libraries of its collaborators; (2) as well as the probability that such a primary hit compound would be developed; (3) tested in clinical trials; (4) approved by the FDA; and (5) marketed successfully to; (6) become one of the top 300 drugs sold in the US. Whatever statistical basis may have been offered to support these assumptions, it is difficult to see how such testimony avoids lapsing into pure speculation, vague estimation and/or gross extrapolation, all of which are arguments and forms of evidence completely contrary to the CAFC’s rule as set forth in Grain Processing Corp. v. Am. Maize-Prods. Co.,[30] and Oiness v. Walgreen Co.[31]

 

In summary, it seems doubtful that an award of royalties on projected future sales of as-yet undiscovered drugs will pass the test of “reasonable, objective foreseeability” articulated in Rite-Hite.[32]

 

So why are agreements still successfully concluded that include a negotiated reach-through royalty? `Reach-through licensing' can be defined as licensing of technology and/or intellectual property, typically patent rights, that includes reach-through royalties based on a percentage of sales of a product, where the licensed technology/intellectual property, such as a patent or basic research, is not incorporated into the end product.  Usually, the value of basic research cannot be reliably forecast at the time of the license negotiation and is not known with certainty until after production of the end product. Thus, reach-through licensing may be the only way for licensor and licensee to agree on how to compensate for use of a basic research invention in the quest for a novel drug product. Of course, the parties can always agree to wholly or partially liquidate a royalty to a present lump sum through agreement on one or more up-front or milestone payments in order to re-allocate the share of the risks in the development process since odds are against the licensor for ultimate recovery based on success of the discovery, development, approval, and marketing process.

 

Secondly, the ability to avoid the uncertainty of a court award of a reasonable royalty , trebled for willful infringement, plus attorney fees (for both the drug developer and the patentee in litigating the matter) and a permanent injunction against making, using, selling or offering for sale the drug, coupled with the certainty of being able to proceed with development of the drug beyond the enabling technology, easily could be worth a reach-through royalty to a risk-averse licensee.

 

Thirdly, if the basic technology enables the development of a drug, it is likely the drug developer will surround the drug with other patents that will probably have a longer life than the patent on the enabling technology, such as patents on the active compound of the drug and method of use patents. The patent term is currently 20 years from filing. It usually takes about three years for a patent to issue and approximately five to seven years (or longer) for a drug to be developed and brought to market. It will be in those five to seven years that the drug developer will file for the surrounding patents. Thus, for example, payments of the agreed reach-through royalty may not begin until the tenth year of the patent on the enabling technology, i.e. the reach-through royalty may be for only about the latter 10 years of the patent on the enabling technology. However, owing to the surrounding patents and market forces, the market for the drug can last much longer than the term of the patent on the enabling technology. That means that the drug developer might realize for example a US$1bn per year market for 15 years, or US$15bn, arguably due to the enabling technology, yet have an outlay of reach-through royalties of only US$25-50m (at 0.25 or 0.50 per cent royalty for only ten years) or US$100-300m (at 1-3 per cent royalty). This is arguably a token amount considering that without the enabling technology the US$15bn in sales would never have been realized at all.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


[1] Utility Examination Guidelines, 66 Fed. Reg. 1092 (Jan. 5, 2001)[hereinafter the Utility Guidelines]; Guidelines for Examination of Patent Applications Under the 35 U.S.C. section 112, paragraph 1, “Written Description” Requirement, 66 Fed. Reg. 1099 (Jan. 5, 2001)[hereinafter the Written Description Guidelines]. The statutory basis for the utility requirement is 35 U.S.C. section 101, which requires that a patentable invention be “useful”.  35 U.S.C. section 101, (2000). The statutory basis for the written description requirement is 35 U.S.C. section 112, paragraph 1, which requires that the patent application contain a written description of the invention. 35 U.S.C. section 112, paragraph 1 (2000).

[2] In re Brana, 51 F.3d 1560, 1564, 34 U.S.P.Q.2d 1436, 1439 (Fed. Cir. 1995) (“Obviously, if a claimed invention does not have utility, the specification cannot enable one to use it.”).

[3] 33 F.3d 1526 (Fed. Cir. 1994).

[4] Brooktree Corp. v. Advance Micro Devices, Inc., 977 F.2d1555, 1571, 24 U.S.P.Q.2d 1401, 1412 (Fed. Cir. 1992)

[5] Cross v. Iuzuka, 753 F.2d 1040, 1051, 224 U.S.P.Q. 739, 747-48 (Fed. Cir. 1985). The CAFC has taken positions consistent with Cross in other cases in which in vitro testing was at issue in the context of utility. See.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 39 U.S.P.Q.2d 1895 (Fed. Cir. 1996)

[6] Brana, id.

[7] Vas-Cath v. Mahurkar, 935 F.2d 1555 (Fed. Cir) 1991.

[8] 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997)

[9] Lockwood v. American Airlines, Inc., 107 F.3d 1565, 41 U.S.P.Q.2d 1961 (Fed. Cir. 1997).

[10] 984 F.2d 1164, 25 USPQ2d 1601 (Fed. Cir. 1993).

[11] 379 F.2d 990154 USPQ118 (CCPA) 1967).

[12] 858F.2d 731, 8 USPQ 2d 1400 (Fed. Cir.1988).

[13] 230 USPQ 546 (Bd. Patt. App & Int. 1986).

[14] Tri-Lateral Project B3b: Mutual Understanding in Search and Examination. Report on Comparative Stud on Biotechnology Patent Practices. There: Comparison Study on “Reach-Through Claims”. www.uspto.gov/web/tws/index.html .

5 F.3d 1013, 62 USPQ2d 1289 (Fed. Cir. 2002)

[16] No. 02-1011 (Fed. Cir. Jan. 13, 2003

[17] 377 U.S. 476, 84 S.Ct. 1526 (1964), 507, 141 U.S.P.Q. at 694.

[18] 56 F.3d 1538 (Fed. Cir. 1995),

[19] 718 F.2d 1056 (Fed. Cir. 1983).

[20] 718 F.2d 1075, 1078, 219 U.S.P.Q. 679, 682 (Fed. Cir. 1983).

[21] 318 F. Supp. 1116 (SDNY 1970), modified and aff'd, 446 F.2d 295 (2d Cir.), cert. denied, 404 US 870 (1971).

[22] 727 F.2d 1506 (Fed. Cir. 1984), cert. denied, 469 US 871 (1984).

[23] Donald R. Ware Research Tool Patents: Judicial Remedies AIPLA Q.J. Vol. 30:267-306.

[24] 35 U.S.C. § 284.

[25] 35 U.S.C. § 285/

[26] 228 F.3d 1338, 1342, 56 U.S.P.Q.2d 1332, 1334 (Fed. Cir. 2000)

[27] 95 F.3d 1109, 1121, 40 U.S.P.Q.2d 1001, 1010 (Fed. Cir. 1996)

[28] 225 F.3d 1349, 1352, 55 U.S.P.Q.2d 1927, 1928 (Fed. Cir. 2000).

[29] The reader should note that the SIBIA case opinion from the District Court trial where the reach through damages were awarded cannot be cited for any precedential value since it was not selected for publication in an official reporter. There is, in fact, a published District Court case that holds that SIBIA cannot be cited as precedent. Mikohn Gaming Corp. v. Acres Gaming Inc. 50 U.S.P.Q.2d 1783 (D.C. Nev. 1998).

[30] 185 F.3d 1341, 1350, 51 U.S.P.Q.2d 1556, 1562 (Fed. Cir. 1999).

[31] 88 F.3d 1025, 1029, 39 U.S.P.Q.2d 1304, 1307 (Fed. Cir. 1996).

[32] See Donald R. Ware Research Tool Patents: Judicial Remedies AIPLA Q.J. Vol. 30:267-306.