Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
Applicant’s remarks and amendments to the claims filed 12/01/2025 have been acknowledged. Claims 42 and 46 have been amended. Claim 47 has been canceled. Claim 48 is newly added.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 42, 46, and 48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
As presently written, claim 42 fails to provide sufficient structural details for the genus of anti-CD79 antibodies comprising up to two conservative amino acid substitutions in in both the VH and VL domains that correlate with the function of binding to CD79 with an affinity of between 2.0 and 300 nM and treating rheumatoid arthritis, systemic lupus, or type I diabetes in a subject. Claims 46 and 48 do not cure the deficiencies of claim 42 and are thus also rejected.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
It is well-known in the art that, in order to bind antigen, an antibody or antigen-binding fragment must have six complementarity defining regions (CDRs) (Janeway, see selection, in particular section 3-6). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chain, and not either alone, that determines the final antigen specificity. As presently written, however, the claims fail to sufficient structural details for the genus of anti-CD79 antibodies having up to two conservative amino acid mutations in the VH and VL domains that correlate with the function of binding to CD79 with an affinity of between 2.0 and 300 nM in order to treat rheumatoid arthritis, systemic lupus, or type I diabetes in a subject.
The conserved amino acid substitutions can be present in the CDRs and/or framework regions of the VH and VL chains. However, there is no guidance provided in the specification about which specific amino acids can vary in the VH and VL chains of the claimed antibodies such that the ability of the antibody to bind to CD79 with an affinity of between 2.0 and 300 nM and treat rheumatoid arthritis, systemic lupus, or type I diabetes in a subject is retained. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to readily identify without further testing which antibodies comprising VH and VL chains each having at most two conservative amino acid substitutions relative to the recited amino acid sequences possess/retain the functional properties of binding to CD79 with an affinity of between 2.0 and 300 nM and treating rheumatoid arthritis, systemic lupus, and type I diabetes in a subject.
While Applicant has disclosed anti-CD79 antibody humanized variants (see, e.g. Para. 0062), such disclosure does not adequately represent the structural diversity of the broad genus of anti-CD79 antibody variants having up to two conserved amino acid substitutions anywhere in the recited VH and VL chain sequences correlated with the functional property of binding to CD79 with an affinity of between 2.0 and 300 nM and treat rheumatoid arthritis, systemic lupus, and type I diabetes in a subject. In addition, there does not appear to be any examples in the prior art anti-CD79 antibody variants encompassed by claim 42 that have the functional properties recited.
Claim 46 further limits the binding affinity of the anti-CD79 variant recited in claim 42 and thus does not cure the deficiencies of the claim 42 discussed above. Claim 48 generally defines the type of conservative amino acid substitutions for a given amino acid such as alanine but does not further identify specific position and type of amino acid substitutions present in the VH and VL chains of the claimed antibody variants that confer binding to CD79 with an affinity between 2.0 and 300 nM. As such, claims 46 and 48 are also rejected.
Therefore, the claimed genus of anti-CD79 antibodies comprising up to two conserved amino acid substitutions in the VH and VL chains lacks adequate written description because there does not appear to be any correlation between the structure of the claimed antibody variants and the function of binding to CD79 with an affinity of between 2.0 and 300 nM in order to treat rheumatoid arthritis, systemic lupus, or type I diabetes in a subject. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of anti-CD79 antibody variants at the time the instant application was filed.
Response to Arguments
Applicant's arguments filed 12/01/2025 have been fully considered but they are not persuasive.
With respect to rejections made under 35 U.S.C. 112(a) written description, Applicant states that "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice . . . , reduction to drawings . . . , or by disclosure of relevant, identifying characteristics, ... , or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus." See Regents of the University of California v. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; M.P.E.P § 2163(II)(3)(a)(ii). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. Id. Moreover, Applicant states that the Federal Circuit has found that "[i]t 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." Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005).
In particular, Applicant argues that as amended claim 42 satisfies the written description requirement, stating that artisans would recognize that the anti-CD79 antibodies encompassed by claim 42 have a high degree of structural similarity to the anti-CD79 antibodies made and tested in Applicant's Specification since the claimed heavy chain and light chain variable regions differ from a recited sequence by, at most, two conservative amino acid substitutions, wherein the term 'conservative substitution' refers to substitution of an amino acid in a polypeptide with a functionally, structurally or chemically similar natural or unnatural amino acid” as set forth by the Specification. Thus, Applicant asserts that in view of such similarities, artisans would not expect the properties of the recited anti-CD79 antibodies, such as binding affinity to CD79, to differ significantly from the anti-CD79 antibodies exemplified in Applicant's Specification. Moreover, Applicant notes that a reduction to practice of every member of a genus is not required; thus, Applicant respectfully submits that the Examiner has not overcome the presumption that an adequate written description of the claimed invention is present when the application is filed. See, In re Wertheim, 541 F.2d 257, 263, 191 USPQ 90, 97 (CCPA 1976).
In response to Applicant’s arguments, the Examiner acknowledge that while a “representative number of species” for a genus claim does not require individual support or reduction to practice for every single species within that genus, the written description must still adequately reflect the structural diversity of the claimed genus to demonstrate possession of the invention See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014). When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). For inventions in an unpredictable art, in particular, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Indeed, the Federal Circuit has found that “a patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.” Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (emphasis added). In particular, “[a] patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (MPEP 2163).
In the context of antibody-antigen interactions, the effect of amino acid mutations on binding affinity is not readily predictable. For example, site-directed mutagenesis studies of the NC10 scFv antibody fragment revealed that the tyrosine at position 32 (TyrL32) is a critical residue for binding to influenza virus neuraminidase since mutation of the TyrL32 residue to phenylalanine (a conservative amino acid substitution) resulted in a significant reduction in binding affinity (Dougan et al, see Abstract). Thus, even a single conservative amino acid substitution at a critical residue can significantly reduce or abolish binding to target antigen.
The specification does not disclose sufficient species representative of the full scope of the claimed genus of anti-CD79 antibody variants correlated with the recited functional properties nor does it establish that conservative amino acid substitutions in the recited VH and VL domains of the antibody variants predictably results in the claimed functional outcomes, specifically binding to CD79 with an affinity of between 2.0 and 300 nM in order to treat rheumatoid arthritis, systemic lupus, and type I diabetes in a subject.
Lastly, Capon states that “it is not necessary that every permutation within a generally operable invention be effective…provided that the effect is sufficiently demonstrated to characterize a generic invention.”(emphasis added). Here, there is no evidence provided in the specification that anti-CD79 antibodies representative of the claimed variants having up to two conserved amino acid substitutions possess the recited functional properties such that general operability can be asserted. As discussed above, a single amino acid substitution in the antibody-antigen interface –even if conservative – can significantly disrupt or abolish antigen binding. As such, not all antibody variants can be considered “generally operable inventions”. Determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves; and for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession (MPEP 2163). The level of skill and knowledge in the art is such that one of ordinary skill would not be able to readily identify without further testing which claimed antibody variants possess/retain the recited functional properties.
A description as filed is presumed to be adequate, unless or until sufficient evidence or reasoning to the contrary has been presented by the examiner to rebut the presumption. See, e.g., In re Marzocchi, 439 F.2d 220, 224, 169 USPQ 367, 370 (CCPA 1971) (MPEP 2163.04) (emphasis added). In view of the above, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of anti-CD79 antibody variants at the time the instant application was filed. Therefore, the rejection made under 35 USC 112(a) written description is maintained.
Conclusion
Claims 22-24 and 28-41 are allowable. Claims 42, 46, and 48 are not allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/LIA E TAYLOR/Examiner, Art Unit 1641 /MICHAEL SZPERKA/Primary Examiner, Art Unit 1641