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 .
Status of Claims
The amended claims filed 12/18/2025 are acknowledged and entered.
Claims 1-4 have been amended
Claims 1-20 are pending and examined on their merits.
Response to Amendment
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Objections
Specification - Withdrawn
The disclosure was objected to because of the following informalities:
a) The use of the term(s), which are a trade name or a mark used in commerce,
Applicant has corrected the informalities in the substitute specification and the objection is withdrawn.
Claim 1 is objected to because of the following informalities: claims 1 recites “….a VL-CDR2 sequence of selected from the group consisting of: SEQ ID NOs: 9, 19, 29, 39, 49, 59, 69, 79, and 89; and a VH-CDR3 sequence selected from the group consisting of: SEQ ID NOs: 10, 20, 30, 40, 50, 60, 70, 80, and 90”. The VH-CDR3 term seems to be a typo as it should be VL-CDR3 based on the recitation of VL-CDR2 is withdrawn in view of applicant’s amendment of claim 1
Claim Rejections - 35 USC § 112 – Withdrawn
The rejection of claims 1-20 under 35 U.S.C. 112(a) because the specification, while being enabling for antibodies characterized as being leptin agonists (S1scAb06, S1scAb11, S2H1, S2H2, S2H3, S2H4, S2H5, S2H6, and S2H7), does not reasonably provide enablement for which combinations of the listed CDR1 and CDR2 and CDR3 sequences for the light chain and which combinations of the listed CDR1 and CDR2 and CDR3 sequences for the heavy chain can be selected and still be able to bind a leptin receptor is withdrawn in view of in view of applicant’s amendment of claim 1.
Claim Rejections - 35 USC § 112 – Improper Markush Grouping - Maintained
The rejection of claims 1-20 on the basis that they contain an improper Markush grouping of alternatives is maintained.
New Rejections Based on Amendments
Objections
Claims
Claim 1, 6 and 7 are objected to because of the following informalities:
Claim 1 is drawn to “An anti-leptin receptor antibody, or antigen binding fragment thereof comprising….”. This recitation’s clarity is improved by the following changes: - Adding “monoclonal” to the limitation. So, the recitation reads “An anti-leptin receptor monoclonal antibody, or antigen binding fragment thereof comprising….”.
Claims 6 recites the limitation “….fragmentis…” instead of “….fragment is…”
Claim 7 recites the limitation “…antibodyis…” instead of “….antibody is…”
Appropriate correction is required. Applicant is also requested to ensure there are no more typos in the claims.
Claim Rejections - 35 USC § 112
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.
2. Claims 1, 4-10, 13-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim 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.
Claim 1 recites language that could be amenable to two or more plausible interpretations. For example, the VH CDR2 of SEQ ID NO: 4 is an 8 amino acid long. SEQ ID NO: 4 could be either the full 8 amino acid sequence or a subsequence (truncation) of a VHCDR2 which typically is between 16 to 19 amino acids according to the Kabat numbering scheme. Kabat is the numbering system mentioned in the Specification (page 12lines 7-10). Therefore, claim 1 at least reads on mutated anti-leptin receptor antibodies mutated by truncation. Claims 5-10 and 13-20 are dependent on claim 1 and do not remedy this situation. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
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.
3. Claims 1, 4-10, 13-20 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the elected antibody (S1scAb06) characterized as being leptin agonist, does not reasonably provide enablement for the CDRs as listed in claim 1. These are significantly smaller than the CDR lengths of Kabat CDRs and so would not be expected to confer antigen binding to an antibody framework barring evidence to the contrary, and still be able to bind a conformational epitope and/or the CRH2 domain of a leptin receptor. They amount to no more than mutated Kabat CDRs. 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 or use the invention commensurate in scope with these claims.
Kabat CDR Lengths and Ranges are as follows:
- HCDR1: 5-7 residues; HCDR2: 16-19 residues; HCDR3: 3-19 residues.
- LCDR1: 6, 7, 11, or 12 residues; LCDR2: 7 residues; CDR-L3: 8-10 residues.
The elected antibody (S1scAb06) has the following CDRs residues:
- HCDR1 SEQ ID NO: 3 (8 residues), HCDR2 SEQ ID NO: 4 (8 residues), and HCDR3 SEQ ID NO: 5 (10 residues)
- LCDR1 SEQ ID NO: 8 (7 residues), LCDR2 SEQ ID NO: 9 (3 residues), and LCDR3 SEQ ID NO: 10 (9 residues).
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete (and not truncated) six CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the complete heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30).
Thus, the state of the art recognized that it would be highly unpredictable that a specific antibody comprising truncated parental CDRs would have antigen binding function. The minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of a murine or humanized antibody includes six complete CDRs (three from the heavy chain variable region and three from the light chain variable region) in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function. One of skill in the art would neither expect nor predict the appropriate functioning of the antibody fragments and mutated antibodies of the instant claims as broadly as claimed.
In the case of antibodies, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences USA, Vol., 79, Pg. 1979-1983, 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Therefore, an antibody molecule that encompasses truncated CDRs of the instant claims is not enabled. Also, even a monoclonal antibody comprising the full-length CDRs of claim 1 is not enabled. Barring experimental evidence, such mutated and truncated CDRs would be insufficient to confer antigen binding function.
Not knowing, absent further experimentation, which modifications function and which do not, when, as set forth above, even a single change of an encoded amino acid can unpredictably affect antibody structure and function, leads to one having no predictability or expectation of success for the function of any given antibody modification. Such random experimentation to identify at a later time what structure or fragment or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation.
The specification does not reasonably provide enablement to use the invention of claims 1, 4-10, 13-20 as they are currently written. Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Relevant arguments that apply to new claims
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Applicant’s arguments are as follow:
- Applicant respectfully traverses each of the rejections listed in the Non final action dated 09/25/2025 and addresses them collectively below.
Claim 1 is amended to recite the requisite six VH and VL CDR sequences for each of the exemplified anti- leptin receptor antibodies S1scAb06, S1scAb 11, S2H1, S2H2, S2H3, S2H4, S2H5, S2H6, and S2H7, thus mooting all grounds of rejection. Claims 2 and 4 are amended to depend upon claim 1, and would thus require that the antibodies comprise the requisite six VH and VL CDR sequences for each of S1scAb06, S scAbi 1, S2H1, S2H2, S2H3, S2H4, S2H5, S2H6, and S2H7,thereby retaining the antibodies ability to bind to the target epitope. As stated by the Office, the instant application is "enabling for antibodies characterized as being leptin agonists (S1scAb06, SiscAb11, S2H1, S2H2, S2H3, S2H4, S2H5, S2H6, and S2H7)," which "can promote the growth of leptin-dependent cells (Example 4)." Id. at pages 4 and 6.
Applicant’s arguments have been considered but are not persuasive. The new language in claim 1 causes the issue discussed in the 112b and 112a ( New Rejections Based on Amendments above) and so the full scope of the claims includes antibodies that lack complete six parental CDRs and so this rejection is made.
Regarding the Claim improper Markush grouping, the claims recite “an anti-leptin receptor antibody” this is not an art-recognized class of molecules as defined in MPEP 2117, even if S1scAb06, S1scAb 11, S2H1, S2H2, S2H3, S2H4, S2H5, S2H6, and S2H7 antibodies are only enabled in the specification as being leptin agonists. Applicant has failed to overcome this rejection. Applicant did not set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and did not present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. Simply being leptin agonist does not provide a single structure since these antibodies bind different epitopes.
No arguments were made and so the rejection stands for reasons of record (see Claim Rejections - 35 USC § 112 – Improper Markush Grouping, above).
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Conclusion
No claims are allowed.
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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/IMMA BARRERA/
Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671