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 .
Election/Restrictions
Applicant’s election of Group I and the combination of GAL-FR23 and 10164 in the reply filed on 9/12/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-5, 10, 12, 16, 18-19, 21-22, 26, 28-29, 31-32, and 36-41 are pending. Claims 18, 21-22, 26, 28-29, 31-32, 36, and 38-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim.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 1-5, 10, 12, 16, 19, and 37 are currently under examination.
Information Disclosure Statement
The information disclosure statements filed on 12/2/2022, 1/25/2024, 3/25/2024, and 6/28/2024 have been considered. Signed copies are enclosed.
Specification
The use of the trademark ALEXAFLUOR has been noted in this application in Figure 13. It should be capitalized wherever it appears and be accompanied by the generic terminology.
Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks.
It is noted that the cited occurrence of improper use is only exemplary and applicant should review the specification to correct any other use of trademarks.
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 1-5, 10, 12, 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 polypeptides and biparatopic antibodies that specifically bind two epitopes in the extracellular domain of a fibroblast growth factor receptor 2 (FGFR2), wherein the polypeptide comprises two antigen binding fragments of anti-FGFR2 antibodies. Dependent claims limit the anti-FGFR2 antibodies to M048-DO1, 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.
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 as well as reducing FGFR2 activity and binding with a specific Kd.
The functional characteristics of antibodies (including binding specificity and affinity are dictated on 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.
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 2-4, 12, 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 2, 3, and 12 are indefinite because it is not clear what limitations are engendered by the antibody names M048-DO1, GAL-FR23, 10164, 2B 1.3.12, GAL-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.
Claim 4 is rendered indefinite by the phrase “antibody comprises one or more complementarity determining regions of the antibody”. An antibody would not be an antibody if it did not have at least one complementarity determining region, so it does not make sense to recite this in the claim. Also, while the parent claim does reference antibodies, there are not actually any antibodies claimed. Thus, it is not clear how this limitation would fit into the parent claim.
Claim 19 recites the limitation "the biparatopic antibody" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 37 recites the limitation “antibody" in line 2. There is insufficient antecedent basis for this limitation in the claim. While the parent claim does reference antibodies, there are not actually any antibodies claimed. Therefore, there could not be a composition comprising the antibody that is not present.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected 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. Claim 4 requires that the polypeptide or antibody comprise one or more complementarity determining regions of the antibody. The parent claim requires that the polypeptide comprise antigen binding fragments of anti-FGFR2 antibodies. This necessarily means that at least one CDR is required. Therefore, claim 4 does not further limit the parent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 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.
Claims 1-5, 10, 12, 16, and 37 are rejected 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).
The instant claims are drawn to polypeptides that specifically bind two epitopes in the extracellular domain of a fibroblast growth factor receptor 2 (FGFR2), wherein the polypeptide comprises two antigen binding fragments of anti-FGFR2 antibodies.
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).
Conclusion
No claim is allowed.
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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