Biological Patent Application Practices

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the pathway using a genus of drugs, without specific examples of the claimed genus. The third would claim a method of modulating pathways using a genus of drugs, accompanied with some examples of specific drugs. To summarize, these three categories of functional claiming can be formulated as the following:

Hypothetical claim 1: A method of modulating X pathway by reducing the activity of protein X in the cell.

Hypothetical claim 2: A method of modulating X pathway by inhibiting protein X with a genus of inhibitors Y.

The specification does not disclose any working example of inhibitors Y.

Hypothetical claim 3: A method of modulating X pathway by inhibiting protein X with a genus of inhibitors Y.

The specification discloses some working examples of inhibitors Y.

The details of the disclosure and the scope of the claims correspond well to the process of research and development in biotechnology inventions. At the early stage, a pathway is discovered, important players such as the key enzymes in the pathway are revealed, and the relationship between this pathway and diseases is elucidated. As the research goes on, researchers conceive that a certain class of compounds will potentially inhibit the key enzyme and thus could constitute an effective treatment for diseases. Nonetheless, as is typical for the biotechnology and pharmaceutical industry, no compound is possible prior to a time-consuming and expensive process. If he or she is lucky, a researcher may eventually discover some effective compounds.

Essentially, discoveries of pathways, at the early stage, are “upstream discoveries that may be useful in a variety of different future research paths or for the development of a variety of commercial products.”⁴⁵² Does this kind of discovery, being remote from any commercial development, merit the award of a patent and exclusion rights?

4. Biological Patent Application Practices

Hypothetical claim 2 in subsection 3 closely resembles the selective inhibitor method claimed in Rochester. In Rochester, the claim was directed to “[a] method for selectively inhibiting [enzyme] activity [by] administering a non-steroidal compound . . . ,” without disclosing a single non-steroidal compound.⁴⁵³ Essentially, the University claimed a method of inhibiting the enzyme with a genus of non-steroidal compounds, without disclosing any species. Here, as in Rochester, hypothetical claim 2 does not disclose any specific compound.

452 Arti K. Rai, Regulating Scientific Research: Intellectual Property Rights and the Norms of Science, 94 NORTHWESTERN UNIVERSITY LAW REVIEW 77, 115 (1999).

453 U.S. Patent No. 5,837,479, claim 1, (filed June 7, 1995).

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Thus, under Rochester's no-compound, no-patent rule, a method of modulating X pathway by inhibiting protein X with a genus of inhibitors Y would not meet the standard.

Hypothetical claim 1 claims an even broader scope than the selective inhibitor method claimed in Rochester. By not claiming any genus of compounds in its language, this type of claim in effect covers any genus of compound that modulates the pathway. Thus, the method claim is analogous to “a cure for cancer by utilizing a substance that attacks and destroys cancer cells while leaving healthy cells alone.”⁴⁵⁴ Such a claim is “more theoretical than real,” “such a ‘cure’ is illusory . . . .”⁴⁵⁵ Hypothetical claim 1 would not pass muster under Rochester either.

The fate of hypothetical claim 3 under current written description precedents is uncertain. Unlike hypothetical claim 2, hypothetical claim 3 is supported by some working examples. Should the scope of the claims be limited to the disclosed embodiments? If functional claiming is to be allowed, would this disclosure of working examples overcome the “vague functional description” rejection in Rochester?⁴⁵⁶ The Rochester court left little guidance in determining how many examples are necessary to render the functional description not vague.

Under the “common feature” test, hypothetical claim 1 also fails to satisfy the written description requirement because the defining correlation does not identify the common feature of the structures. First, a biological pathway often has multiple defining materials, and each defining material may define a different class of inhibitors. Second, a complex biological pathway usually comprises multiple sub-pathways. The correlation defined by each sub-pathway is dissimilar to the others, resulting in a different class of inhibitors. Third, because the defining material may be controlled by other cellular constituents, the inhibition of the defining material could be accomplished indirectly by regulating those cellular constituents. The correlation defined by indirect inhibition would differ significantly from the correlation defined by direct inhibition. Due to these variables, it is unlikely that the defining correlation would be of a “complementary structural relationship,”⁴⁵⁷ or “known to those of ordinary skill in the art.”⁴⁵⁸ Further, it is unlikely that there is any common feature among the large variety of inhibitors defined by the multiple correlations.

Hypothetical claim 2, by focusing on one genus of inhibitors, eliminates many variables seen in hypothetical claim 1. There still might be multiple defining materials. But claim 2 is

454 University of Rochester v. G.D. Searle & Co., 249 F. Supp. 2d 216, 228 (W.D.N.Y. 2003).

455 Id.

456 G.D. Searle & Co., 358 F.3d at 928.

457 Enzo Biochem, Inc., 296 F.3d at 1328.

458 In re Wallach, 378 F.3d 1330, 1335 (Fed. Cir. 2004).

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unlikely to involve multiple sub-pathways, and possibly involves only one inhibition mechanism, either direct or indirect.⁴⁵⁹ The “common feature” test would yield a different result from that under the current precedents.

In most cases, the inhibition correlation does not identify a common feature of the structures. The selective COX-2 inhibition method litigated in Rochester, for example, comprises a variety of inhibitors that are dissimilar to each other.⁴⁶⁰ Some selective COX-2 inhibitors are composed of three six-member rings (Etoricoxib) or two six-member rings (Nimesulide, Lumiracoxib), some others are composed of two six-member rings plus one five-member ring (Celecoxib, Rofecoxib, Valdecoxib, Deracoxib, Parecoxib).⁴⁶¹ Without some working examples in each of these classes of inhibitors, an ordinary person skilled in the art has no way to identity a common feature among all selective inhibitors.

In some cases, however, the inhibition correlation may identify a common feature. For example, claim 203 of Ariad's patent claims a method of inhibiting NF-κβ protein by using a nucleic acid decoy molecule. Because NF-κβ protein binds to a specific site of our genome,⁴⁶² a nucleic acid decoy inhibitor works by “directly targeting the DNA-binding activity of individual NF-κβ proteins ....”⁴⁶³ The design of the nucleic acid decoy imitates the sequences in the genome to which NF-κβ protein binds, which contain a portion consensus among all binding sequences.⁴⁶⁴ As a result, the designed decoy molecules are similar to each other, all containing the consensus sequence. Thus, the inhibition correlation does identify a common feature of the decoy structures—the consensus sequence of the binding sites. In this case, even without any working example, a person ordinary skilled in the art could envision the structure of the genus based on the common feature identified. The written description requirement would be satisfied under the proposed test. This approach avoids the arbitrary outcome resulting from the no-compound, no-patent rule.

Under the “common feature” test, the fate of hypothetical claim 3 is more predictable and certain. In cases like the selective COX-2 inhibition method, working examples in each class of inhibitors are needed in order to identity a common feature. In cases like the NF-κβ decoy method, working examples, though not needed, would certainly help the patentee's

459 One of the most common means to inhibit an enzymatic activity is to block a binding pocket or an “active site” of the enzyme—the region of an enzyme at which a chemical reaction occurs, and to render it incapable of functioning in the cell. For example, HIV transcriptase inhibitor and protease inhibitor function by binding to and inhibiting the active sites of HIV transcriptase and protease.

460 Regina M. Rotting, Timothy Hla, & Daniel L. Simmons, Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition, 56 PHARMACOLOGICAL REVIEWS 387, 407 (2004).

461 Id.

462 Cao, Greten, Karin & Li, supra note 478, at 303.

463 Qiutang Li & Inder M. Verma, NF-κβ Regulation in the Immune System, 2 NATURE REVIEWS IMMUNOLOGY 725, 732 (2002).

464 Marzia Bianchi, Rita Crinelli, Lucia Gentilini & Mauro Magnai, Design and Characterization of Decoy Oligonucleotides Containing Locked Nucleic Acids, 20 NUCLEIC ACIDS RESEARCH 2435 (2002).

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argument in fulfilling her disclosure requirement. In other cases, the written description requirement could be met if a sufficient number of working examples would reveal a common feature. For example, there would be pathways where the defining correlation does not itself identify a common feature, in the absence of specific embodiments. With a number of working examples, it becomes clear to an ordinary artisan that the correlation necessarily requires all inhibitors to possess a common structure motif. Then, under the “common feature” test, the written description requirement should be satisfied.