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 .
Applicant’s amendment and remarks filed on 7/10/2026 are acknowledged. Claims 3-4 and 19 are amended. Claims 5, 12, 18, 29, and 39-41 are cancelled. Claims 1-4, 10, 16, 19, 21-22, 26, 28, 31-32, and 36-38 are pending. Claims 21-22, 26, 28, 31-32, 36, and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Claims 1-4, 10, 16, 19, and 37 are currently under examination.
Information Disclosure Statement
The information disclosure statements filed on 1/20/2026, 2/25/2026, and 6/17/2026 have been considered. Signed copies are enclosed.
Objections Withdrawn
The objection to the specification for the use of the trademark ALEXAFLUOR is withdrawn in light of applicant’s amendment thereto.
Claim Rejections Withdrawn
The rejection of claims 1-5, 10, 12, 16, and 37 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of applicant’s amendment thereto and in favor of the new rejection set forth below.
The rejection of claims 2-4, 12, 19, and 37 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the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention is withdrawn in light of applicant’s amendment thereto.
The rejection of claim 4 under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in light of applicant’s amendment thereto.
The rejection of claims 1-5, 10, 12, and 16 under 35 U.S.C. 102(a)(1) as being anticipated by Harrenga et al (US Patent Application Publication 2014/0322220; IDS filed 12/2/2022) is withdrawn in light of applicant’s amendment thereto.
Claim Rejections Maintained
35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The rejection of claim 37 under 35 U.S.C. 102(a)(1) as being anticipated by Harrenga et al (US Patent Application Publication 2014/0322220; IDS filed 12/2/2022) is maintained for the reasons set forth in the previous office action. The rejection has been updated to reflect applicant’s claim amendments.
The instant claim is drawn to a pharmaceutical compositions comprising a biparatopic antibody that specifically binds two epitopes in the extracellular domain of a fibroblast growth factor receptor 2 (FGFR2) or an antigen binding fragment thereof.
Harrenga et al disclose bispecific antibodies which contain CDRs or VH or VL chains from the antibody M048-D01 (see paragraph 0064 and claims 5-7). These antibodies bind to the extracellular domain of FGFR2 and, since the specification defines a CDR as an antigen binding fragment of an antibody, the disclosed antibodies would necessarily have at least two antigen binding fragments of the recited antibodies. The disclosed antibodies also contain detectable amino acid sequences because any sequence large enough can be detected. Further, the antibodies can be in a pharmaceutically acceptable carrier with a pharmaceutical excipient (see paragraph 0030). In addition. Harrenga et al disclose FGFR2 binding antibody GAL-FR23. A composition containing this antibody would be a composition that comprises an antigen binding fragment of the biparatopic antibody of instant claim 1.
Applicant’s arguments all rely on whether or not Harrrenga discloses biparatopic antibodies as disclosed in claim 1.
This is not persuasive because claim 37 does not require a biparatopic antibody; it instead only requires an antigen binding fragment of antibody GAL-FR23, antibody 12433, antibody 2B 1.3.12, antibody 10164, or antibody HuGA:-FR21.
New Claim Rejections
35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 10, 16, and 37 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to biparatopic antibodies that specifically bind two epitopes in the extracellular domain of a fibroblast growth factor receptor 2 (FGFR2), wherein the antibody comprises two antigen binding fragments which bind to epitopes targeted by antibodies GAL-FR23, 10164, 2B 1.3.12, GAL-FR21, and 12433.
Though these specific antibodies are recited in the claims and specification, these antibody names reference a very broad genus of antibodies since they are only required to have 85% sequence homology with antibodies that have been deposited. There are trillions of trillions of antibodies encompassed just by applicant’s reference to GAL-FR23. This does not include the possible combinations of that astronomical number with the astronomical number of the other possible antibodies. This also only considers the use of the entire VH chain. When one considers the fact that only a single CDR from any two anti-FGFR2 antibody is required, the number of polypeptides encompassed by the claims is beyond astronomically large. The specification only describes a few of these. More importantly, only claim 4 actually requires these named antibodies. All of the other claims require an antibody that binds to the same epitopes as the named antibodies. For claim 4, while specific antibodies are named, only 90% sequence identity with the variable sequences of these antibodies is required.
The claims require various functional characteristics of the above polypeptides, including the ability to bind specifically to two epitopes in the extracellular domain of FGFR2, binding of the same epitopes as the named antibodies, and as reducing FGFR2 activity and binding with a specific Kd.
The functional characteristics of antibodies (including binding specificity and affinity are dictated by their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416) teaches that, “ … Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site." The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
The claims encompass an extremely large number of variants that have specific required functions. The specification discloses only very few species within the instant claims scope and does not provide any guidance as to which amino acids can be varied while retaining the appropriate affinity or ability to neutralize protective antigen.
Therefore, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Applicant argues: That the claims have been amended to address the rejection and that the antibodies provided in the application allow a skilled practitioner in the art to recognize, understand, and appreciate the nature of the biparatopic antibodies and their binding properties as recited in the claims.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons: As discussed above in the rejection, the amendment does not address the issues in the claims.
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.
Claims 1-2, 10, 16, 19, and 37 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 pre-AIA the applicant regards as the invention. Claims not specifically mentioned below are included because they contain the issue of the parent claim.
Claim 1 is because it is not clear what limitations are engendered by the antibody names GAL-FR23, 10164, 2B 1.3.12, HuGAL-FR21, and 12433. Pages 7-10 provide descriptions of these antibodies. However, these pages do not actually define limits of what constitutes a given antibody with these names. For example, GAL-FR23 is defined as an antibody or antigen binding fragment thereof having at least about 85% amino acid sequence identity to the antibody produced by the hybridoma deposited as PTA-9408. The specification later provides a single VH and VL sequence for antibody GAL-FR23. Therefore, the antibody appears to be defined by a sequence, but then also not defined by that sequence.
Applicant argues: That the claims are amended such that they are directed to biparatopic antibodies which comprise two antigen binding fragments of anti-FGFR2 antibodies that are specified in the claims.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons: The claims still recite the indefinite language and applicant’s arguments do not actually address the issue raised in the rejection.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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