DETAILED ACTION
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 .
Claim Status
The preliminary amendment filed 5/22/24 is acknowledged. Claims 4-9, 11, 13, 15-18, 20-22, 28, and 35 are amended. Claims 24-27, 32-34, and 36-41 are cancelled. Claims 1-23, 28-31, and 35 are pending and examined.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 5 and 8 are objected to because of the following informalities: The claims recite CoTH3 binding agents that comprise SEQ ID NOs selected from Tables 2 and 4. Claims must be complete in themselves and clearly define the invention without relying on external references such as figures or tables, absent exceptional circumstances. The recited tables each have less than 10 elements per column, and can therefore be recited in the claims. Appropriate correction is required.
Claim 7 is objected to because it recites wherein the binding agent comprises a human heavy chain constant “regions.” This is an incorrect use of plurality. Appropriate correction is required.
Claim Rejections - 35 USC § 112b
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 29 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention. Regarding claim 29, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Description of examples or preferences is properly set forth in the specification rather than the claims. See MPEP § 2173.05(d).
Therefore, claim 29 is rejected under 35 U.S.C. 112(b) for being indefinite.
Claim Rejections - 35 USC § 112a
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, 5-23, 28-31, and 35 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.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 claimed genus MPEP 2163(II)(3)(a)(i)(C).
Independent claim 1 recites a CotH3 binding agent comprising CDRs having at least 80% identity to the recited SEQ ID NOs, as well as numerous combinations of those CDR sequences, which encompasses a large genus of potential amino acid sequences. The specification, however, only describes a limited number of specific variable heavy and variable light chain embodiments comprising particular CDR sequences, primarily enumerated in Tables 2, 4, and 7, and corresponding binding data. These functional variants include the exact CDR combinations claimed in claims 2-4 and the combinations of those variable heavy and variable light chain CDRs [see Table 7]. As discussed above, the claims are not limited to those species, but also include many possible substitutions, deletions, and insertions within each CDR sequence, notwithstanding all of the possible CDR sequence combinations. Crucially, protein chemistry is unpredictable and the art recognizes that even a single amino acid substitution can abolish protein activity [see Rudikoff et al., abstract]. As such, the specification fails to provide a representative number of species within the recited genus, adequate structure-function correlation, or other identifying characteristics of the genus as a whole, and accordingly, the disclosure does not reasonably convey possession of the full scope of possible CDR combinations and amino acid modifications. Claims 6-23, 28-31, and 35 either explicitly or implicitly require the composition of claim 1 but do not materially limit the genus of agents and are therefore included in this rejection.
Similarly, claim 5 recites a binding agent comprising a variable light chain region (VL) and variable heavy chain region (VH) at least 80% similar to SEQ ID NOs selected from Tables 2 and 4. While the specification provides support for three possible combinations with binding activity [see table 7], it does not provide support for all possible combinations. Further, embodiments such as those comprising SEQ ID NO: 24 and SEQ ID NO: 14 lacks support indicating it was generated or contemplated. Further still, the specification does not provide support for all possible additions, deletions, and substitutions while maintaining 80% similarity and retaining the claimed binding function as discussed above. In fact, the specification demonstrates that COTH3 agent binding is highly sensitive to sequence changes to framework regions, with the initial CDR-grafted humanized antibody exhibiting no detectable binding [see table 5] and requiring applicant to perform structural remodeling to several specific positions of the framework region to identify three functional variants [see Table 7]. These results indicate that small modifications to even the framework regions can have unpredictable effects on antigen binding. The specification fails to provide a representative number of species within the recited genus, adequate structure-function correlation, or other identifying characteristics of the genus as a whole. Accordingly, the disclosure does not reasonably convey possession of the full scope of possible VH and VL combinations in addition to possible amino acid modifications.
Therefore, 1, 5-23, 28-31, and 35 rejected under 35 U.S.C. 112(a) for lack of written description.
Claims 1, 5-23, 28-31, and 35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the check marked antibodies listed in Table 7, which comprise the CDRs of claims 2 and 3, does not reasonably provide enablement for all possible binding agents comprising CDR sequences at least 80% identical to the recited CDR sequences in claim 1, nor the numerous possible combinations of said sequences when selecting a set of three. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims. The specification provides guidance for only a limited number of antibody embodiments and does not teach how to identify which 80% identity variants or additional CDR combinations will retain CotH3 binding without undue experimentation. As discussed above, even a single amino acid change to a sequence may abolish binding, and restoration of binding required structural remodeling, framework back mutations, and construction of numerous heavy and light chain variants before identifying functional proteins. Accordingly, undue experimentation would be required to practice the full scope of claim 1. For all of the same reasons as above, claim 5 is similarly rejected. Claims 6-23, 28-31, and 35 either explicitly or implicitly require the composition of claim 1 but do not materially limit the genus of agents and are therefore included in this rejection.
Therefore, claims 1, 5-23, 28-31, and 35 are rejected under 35 U.S.C. 112(a) for lack of enablement.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tirone D Johnson whose telephone number is (571)272-1256. The examiner can normally be reached M-F, 9-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIRONE D. JOHNSON/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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