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Archived updates for Friday, August 12, 2005

Full Chimeric Nucleotide Sequences Not Required for Written Description, Enablement Another Story


In Capon, et al. v. Eshhar, et al. v. Dudas (Fed. Cir., August 12, 2005) Judge Newman considered whether the nucleotide sequence of a chimeric gene (an artificial gene that combines segments of DNA in a way that does not occur in nature) must be fully presented in order to satisfy the written description requirement of 35 USC §112, even though the nucleotide sequences of the component DNA are already known. According to the court:

"The Board's rule that the nucleotide sequences of the chimeric genes must be fully presented, although the nucleotide sequences of the component DNA are known, is an inappropriate generalization. When the prior art includes the nucleotide information, precedent does not set a per se rule that the information must be determined afresh. Both parties state that a person experienced in the field of this invention would know that these known DNA segments would retain their DNA sequences when linked by known methods. Both parties explain that their invention is not in discovering which DNA segments are related to the immune response, for that is in the prior art, but in the novel combination of the DNA segments to achieve a novel result."

After concluding that the Board erred in holding that the specifications did not meet the written description requirement, the court went on to consider whether the specifications adequately support the breadth of all of the claims that were presented:

It is well recognized that in the "unpredictable" fields of science, it is appropriate to recognize the variability in the science in determining the scope of the coverage to which the inventor is entitled. Such a decision usually focuses on the exemplification in the specification. See, e.g., Enzo Biochem, 296 F.3d at 1327-28 (remanding for district court to determine "[w]hether the disclosure provided by the three deposits in this case, coupled with the skill of the art, describes the genera of claims 1-3 and 5"); Lilly, 119 F.3d at 1569 (genus not described where "a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus" had not been provided); In re Gostelli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (two chemical compounds were insufficient description of subgenus); In re Smith, 458 F.2d 1389, 1394-95 (CCPA 1972) (disclosure of genus and one species was not sufficient description of intermediate subgenus); In re Grimme, 274 F.2d 949, 952 (CCPA 1960) (disclosure of single example and statement of scope sufficient disclosure of subgenus).

Precedent illustrates that the determination of what is needed to support generic claims to biological subject matter depends on a variety of factors, such as the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, the predictability of the aspect at issue, and other considerations appropriate to the subject matter. See, e.g., In re Wallach, 378 F.3d 1330, 1333-34 (Fed. Cir. 2004) (an amino acid sequence supports "the entire genus of DNA sequences" that can encode the amino acid sequence because "the state of the art has developed" such that it is a routine matter to convert one to the other); University of Rochester, 358 F.3d at 925 (considering whether the patent disclosed the compounds necessary to practice the claimed method, given the state of technology); Singh v. Brake, 317 F.3d 1334, 1343 (Fed. Cir. 2002) (affirming adequacy of disclosure by distinguishing precedent in which the selection of a particular species within the claimed genus had involved "highly unpredictable results").

It is not necessary that every permutation within a generally operable invention be effective in order for an inventor to obtain a generic claim, provided that the effect is sufficiently demonstrated to characterize a generic invention. See In re Angstadt, 537 F.2d 498, 504 (CCPA 1976) ("The examples, both operative and inoperative, are the best guidance this art permits, as far as we can conclude from the record"). While the Board is correct that a generic invention requires adequate support, the sufficiency of the support must be determined in the particular case. Both Eshhar and Capon present not only general teachings of how to select and recombine the DNA, but also specific examples of the production of specified chimeric genes. For example, Eshhar points out that in Example 1 of his specification the FcR? chain was used, which chain was amplified from a human cDNA clone, using the procedure of Kuster, H. et al., J. Biol. Chem., 265:6448-6451 (1990), which is cited in the specification and reports the complete sequence of the FcR? chain.

Eshhar's Example 1 also explains the source of the genes that provide the heavy and light chains of the single chain antibody, citing the PhD thesis of Gideon Gross, a co-inventor, which cites a reference providing the complete sequence of the Sp6 light chain gene used to construct the single-chain antibody. Eshhar states that the structure of the Sp6 heavy chain antibody was well known to those of skill in the art and readily accessible on the internet in a database as entry EMBL:MMSP6718. Example 5 at page 54 of the Eshhar specification cites Ravetch et al., J. Exp. Med., 170:481-497 (1989) for the method of producing the CD16? DNA clone that was PCR amplified; this reference published the complete DNA sequence of the CD16? chain, as discussed in paragraph 43 of the Eshhar Declaration. Example 3 of the Eshhar specification uses the DNA of the monoclonal anti-HER2 antibody and states that the N29 hybridoma that produces this antibody was deposited with the Collection Nationale de Cultures de Microorganismes, Institut Pasteur, Paris, on August 19, 1992, under Deposit No. CNCM I-1262. It is incorrect to criticize the methods, examples, and referenced prior art of the Eshhar specification as but "a few PCR primers and probes," as does the Director's brief.

Capon's Example 3 provides a detailed description of the creation and expression of single chain antibody fused with T-cell receptor zeta chain, referring to published vectors and procedures. Capon, like Eshhar, describes gene segments and their ligation to form chimeric genes. Although Capon includes fewer specific examples in his specification than does Eshhar, both parties used standard systems of description and identification, as well as known procedures for selecting, isolating, and linking known DNA segments. Indeed, the Board's repeated observation that the full scope of all of the claims appears to be "enabled" cannot be reconciled with the Board's objection that only a "general plan" to combine unidentified DNA is presented. See In re Wands, 858 F.2d 731, 736-37 (Fed. Cir. 1988) (experimentation to practice invention must not be "undue" for invention to be considered enabled).

The PTO points out that for biochemical processes relating to gene modification, protein expression, and immune response, success is not assured. However, generic inventions are not thereby invalid. Precedent distinguishes among generic inventions that are adequately supported, those that are merely a "wish" or "plan," the words of Fiers v. Revel, 984 F.2d at 1171, and those in between, as illustrated by Noelle v. Lederman, 355 F.3d at 1350; the facts of the specific case must be evaluated. The Board did not discuss the generic concept that both Capon and Eshhar described -- the concept of selecting and combining a gene sequence encoding the variable domain of an antibody and a sequence encoding a lymphocyte activation protein, into a single DNA sequence which, upon expression, allows for immune responses that do not occur in nature. The record does not show this concept to be in the prior art, and includes experimental verification as well as potential variability in the concept.

Whether the inventors demonstrated sufficient generality to support the scope of some or all of their claims, must be determined claim by claim. The Board did not discuss the evidence with respect to the generality of the invention and the significance of the specific examples, instead simply rejecting all the claims for lack of a complete chimeric DNA sequence. As we have discussed, that reasoning is inapt for this case. The Board's position that the patents at issue were merely an "invitation to experiment" did not distinguish among the parties' broad and narrow claims, and further concerns enablement more than written description. See Adang v. Fischhoff, 286 F.3d 1346, 1355 (Fed. Cir. 2002) (enablement involves assessment of whether one of skill in the art could make and use the invention without undue experimentation); In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (same). Although the legal criteria of enablement and written description are related and are often met by the same disclosure, they serve discrete legal requirements.
The predictability or unpredictability of the science is relevant to deciding how much experimental support is required to adequately describe the scope of an invention. Our predecessor court summarized in In re Storrs, 245 F.2d 474, 478 (CCPA 1957) that "[i]t must be borne in mind that, while it is necessary that an applicant for a patent give to the public a complete and adequate disclosure in return for the patent grant, the certainty required of the disclosure is not greater than that which is reasonable, having due regard to the subject matter involved." This aspect may warrant exploration on remand.

In summary, the Board erred in ruling that '112 imposes a per se rule requiring recitation in the specification of the nucleotide sequence of claimed DNA, when that sequence is already known in the field. However, the Board did not explore the support for each of the claims of both parties, in view of the specific examples and general teachings in the specifications and the known science, with application of precedent guiding review of the scope of claims.

We remand for appropriate further proceedings.

With the "§112-separatists" now in the clear majority at the Federal Circuit, it would appear that Professor Hal Wegner is facing an uphill battle when he writes that this decision "perpetuates the judicial fiction" that there is a separate written description requirement independent of enablement in the first paragraph of 35 USC §112:

"The Capon standard is unique vis-a-vis Europe and Japan. If it is applied insofar as determining Paris Convention priority, it will create situations where a “home country” application filed in Europe or Japan under local standards may well disclose all elements of the invention as part of the documents as a whole, yet not meet the American standard until the time of the U.S. filing. In such a case, a denial of priority would constitute a violation of Article 4H of the Paris Convention."


And, as if that were not enough, The Good Professor is also calling the decision "a paradigm for de facto secrecy at the PTO and the Federal Circuit:"
"Capon was argued before the court two months before the flurry of opinions
in denial of en banc in the Rochester case that perpetuated Enzo. Yet,
now, more than fifteen (15) months after the argument, and after more than 123
citations in the electronic (Westlaw) literature to Rochester, the Capon
submarine has surfaced for the very first time. The PTO has within its power the
very easy answer to the secrecy problem on appeal: It should require that
an appellant submit a pdf copy to the PTO decision appealed from at the time of
filing the Notice of Appeal; a separate portion of the PTO’s website could be
devoted to such filings."

Contact me for more of The Good Professor's thoughts on this decision.
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2 Comments:

Blogger Andrew Lahser said...

Listen to the Capon v. Eshhar v. Dudas opinion on your iPod or MP3 player.

August 22, 2005 2:21 AM  
Anonymous Anonymous said...

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April 07, 2009 4:34 AM  

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