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 .
DETAILED ACTION
The Amendment filed 10/27/2025 in response to Office Action of 8/1/2025, is acknowledged and has been entered. Claims 1, 4, 7-16, 19, 20, and 25-29 are now pending. Claims 1, 4, 7-8, 10-11, 14-16, and 20 are amended. Claims 25-29 are new.
The 35 U.S.C. 102 and 103 rejections are hereby withdrawn in view of amendments.
Claims 1, 4, 7-8, 10-11, 14-16, 20, and 25-29 are currently being examined.
Maintained Rejection
(Arguments Addressed)
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.
Claims 1, 4, 7-8, 10-11, 14-16, 20, and 25-29 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. This is a WRITTEN DESCRIPTION Rejection.
The claims recite a composition comprising: an antibody that identifies the phosphorylation of HIF-1α by PIM at THr455, wherein said antibody specifically binds to phosphorylated Thr455 of said HIF-1α.
The claims identify the monoclonal antibody by function only, wherein the function is to: (1) bind to phosphorylated Thr455 of HIF-1α, (2) blocks the phosphorylation of HIF-1α by PIM, (3) treating cancer, (4) identifying/detecting the presence of phosphorylation in a sample. Thus, the claims are drawn to any antibody that inhibits the function of HIF-1α, which includes antibodies that binds to HIF-1α, but also any other protein that interacts or involved with the function of HIF-1α. No structure of any monoclonal antibody that inhibits HIF-1α is recited in the claims.
With regards to a monoclonal antibody that inhibits one or more activities of HIF-1α, the instant specification does not disclose any examples of an antibody that functions as claimed.
By the time of the filing of the instant application, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4.
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Epitope Mapping, Biodrugs 2007; 21 (3): 145-156 page 146 section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence and length of VH-CDR3.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al., Benchmarking B cell epitope prediction: Underperformance of existing methods, Protein Science (2005), 14:246–248 pg. 246) . 3D structural analyses of antibody-epitope binding highlighting that the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al.,3D-Epitope-Explorer (3DEX): Localization of Conformational Epitopes within Three-Dimensional Structures of Proteins, Wiley Interscience, 2005 42–44, 60596, page 879).
The structure activity relationship of the CDR antigen binding region that binds HIF-1α is not known and the binding epitopes cannot be predicted based on the antibody sequences.
To provide adequate written description and evidence of possession of the claimed composition antibody genus, the instant specification can structurally describe representative antibodies or antigen binding proteins that function as listed above (1)-(4), or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for antibodies that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The HIF-1α antigen provides no information about the structure of an antibody inhibits it.
Given the lack of representative examples to support the full scope of the claimed antibodies that inhibit one or more activities of HIF-1α, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs of the antibodies that function as claimed, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Response to Arguments
Applicant amended the claims to recite that the antibody binds to HIF-1α and identifies the phosphorylation of HIF-1α by PIM at Thr455 of HIF-1α. Applicant argues that the specification provides extensive experimental discussion on how to make and use such antibodies (pg 18-28 of the specification).
Applicant's arguments filed 10/27/2025 have been fully considered but they are not persuasive. The claims are drawn to any antibody that specifically binds to phosphorylated Thr455 of said HIF-1α. There is no structure of the antibody. One example of the antibody as noted by the Applicant does not provide the full scope of the claimed composition. As noted in the 112(a) written description, it was well established in the art that the formation of an intact antigen-binding site usually requires the association of the complete heavy and light chain variable region of the antibody. The structure of the antibody is necessary in order to determine the function of the antibody.
Conclusion
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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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678