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 without traverse of the invention of Group I, drawn to an anti-FGFR3 antibody or antigen-binding fragment in the reply filed on 03/12/2026 is acknowledged. The applicant further elects without traverse the anti-FGFR3 antibody species F309#SSM236 having the CDRs of SEQ ID NOs: 5, 23, 198, 71, 93, and 114, wherein the anti-FGFR3 antibody is a monoclonal antibody. The elected anti-FGFR3 antibody species was found to be free of the prior art and thus the election requirement for the antibody species is withdrawn.
Claims 8-10, 12, 13, 15-18, 24, 27, 31, 33, 37, 43, 44, and 45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/12/2026.
Claims 1-7, 40, and 42 are examined on the merits in the present Office Action.
Claim Objections
Claim 4 is objected to because of the following informalities: Claim 4 recites that the HCDR3s are selected from SEQ ID NOs: 203-215 and the LCDR3s are selected from SEQ ID NOs: 216 -219. Per tables 8 and 10 of the specification, the amino acid sequences of SEQ ID NOs: 203-215 refer to variable heavy (VH) chains not heavy chain CDRs whereas the amino acid sequences of SEQ ID NOs: 216-219 refer to variable light (VL) chains not light chain CDRs. It is believed that the HCDR3s intended to be SEQ ID NOs: 186-198 (Table 7) and the LCDR3s intendent to be SEQ ID NOs: 199-202 (Table 9) since these CDRs are present in the VH and VL chains currently recited in the claims. Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities: Tables 5A-5D, 6, and 11-13 are unreadable.
Appropriate correction is required.
Drawings
The drawings are objected to because multiple figures are blurry or unreadable, including Figures 1A-1D, 3B, 4B, 5, 8, 9A, 9C, 12, 13A, 15A, 15B, 15C, 16A, 16B, 16C, 17, 19, 20, 25, 27, and 30. It is requested that Applicant make corrections to any and all figures that are unreadable. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings, in particular Figure 9C, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
Written Description
Claims 1-3, 5-7, 40, and 42 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.
Claim 1 allows the CDRs of different anti-FGFR3 antibody clones to be interchanged, yet there is no evidence that CDRs from structurally distinct anti-FGFR3 parental clones can be interchanged without negatively impacting binding affinity as it does not appear that each clone is a variant/mutant of a single starting clone. Further, there is no guidance provided in the specification regarding how CDRs from different anti-FGFR3 parental clones can be interchanged such that binding to FGFR3 is maintained. Claims 2, 3, 5, 6, 7, 40, and 42 incorporate limitations of claim 1 but do not cure the deficiencies of claim 1 and thus are also rejected.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, 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 genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description 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.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
Claim 1 allows the CDRs of different anti-FGFR3 antibody clones to be interchanged, yet there is no evidence that CDRs from structurally distinct anti-FGFR3 parental clones can be interchanged without negatively impacting binding affinity as it does not appear that each clone is a variant/mutant of a single starting clone. Further, there is no guidance provided in the specification regarding how CDRs from different anti-FGFR3 parental clones can be interchanged such that binding to FGFR3 is maintained. Claims 2, 3, 5, 6, 7, 40, and 42 incorporate limitations of claim 1 but do not cure the deficiencies of claim 1 and thus are also rejected.
The specification describes the final identification and selection of 25 FGFR3-specific antibody clones as disclosed in Tables 1-4 through different screening techniques (see Examples 1-5). Additional variants were designed from the parent clone F309 through affinity maturation engineering (Example 21). The F309 variants have the HCDR3 sequences of SEQ ID NOs: 186 to 198 and the LCDR3 sequences of SEQ ID NOs: 199-202 as recited in the instant claims (see Tables 7-10). While the specification discloses the sequences of different anti-FGFR3 parental clones and variants of F309, the specification does not demonstrate or provide evidence that CDRs from different parental clones can be interchanged with each other without substantially impacting the ability of the resulting antibody to bind to FGFR3 as it does not appear that each clone are variants/mutants of a single starting clone with the exception of F309 and its variants. Nor does the specification provide any guidance for predicting which CDR combinations from different parental clones would be operable across the claim scope. Without further guidance, artisans could not readily determine which CDRs of different anti-FGFR3 parental clones can be interchanged such that binding affinity for FGFR3 is maintained. Additionally, given the number of CDR combinations possible, claim 1 encompasses anti-FGFR3 antibodies. not presently disclosed in specification; and there is no evidence provided in the specification of other antibodies comprising CDR combinations not presently disclosed but encompassed by the claims that have the functional property of binding to FGFR3. Claims 2, 3, 5, 6, 7, 40, and 42 incorporate limitations of claim 1 but do not cure the deficiencies of claim 1 and thus are also rejected.
Therefore, the claimed genus of anti-FGFR3 antibodies lacks adequate written description because there does not appear to be any correlation between the structure of the claimed antibodies and the function of binding to FGFR3. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of anti-FGFR3 antibodies at the time the instant application was filed.
Scope of Enablement
Claims 1-3, 5-7, 40, and 42 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 anti-FGFR3 antibody molecules with compatible CDRs derived from their respective parental clones (or variants thereof), does not reasonably provide enablement anti-FGFR3 antibodies formed by interchanging CDRs from different parental clones. 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.
The nature of the invention relates to anti-fibroblast growth factor receptor 3 (FGFR3) antibody or antigen-binding fragments thereof and their use in the treatment of cancer, an inflammatory disease, or an immune disease.
Claim 1 is broadly drawn to a conjugate compound comprising one or more VHH molecules and at least one therapeutic compound or vehicle comprising such a therapeutic compound, wherein the CDR from multiple structurally distinct VHH clones can be interchanged. Thus, the claim encompasses numerous possible CDR combinations beyond the specific parental clones and variants disclosed in the specification.
The specification describes the final identification and selection of 25 FGFR3-specific antibody clones as disclosed in Tables 1-4 through different screening techniques (see Examples 1-5). Additional variants were designed from the parent clone F309 through affinity maturation engineering (Example 21). The F309 variants have the HCDR3 sequences of SEQ ID NOs: 186 to 198 and the LCDR3 sequences of SEQ ID NOs: 199-202 as recited in the instant claims (see Tables 7-10). While the specification discloses the sequences of different anti-FGFR3 parental clones and variants of F309, the specification does not demonstrate or provide evidence that CDRs from different parental clones can be interchanged with each other without substantially impacting the ability of the resulting antibody to bind to FGFR3 as it does not appear that each clone are variants/mutants of a single starting clone with the exception of F309 and its variants. Nor does the specification provide any guidance for predicting which CDR combinations from different parental clones would retain binding activity across the claim scope.
It is well-known in the art that, in order to bind antigen, a conventional antibody or antigen-binding fragment must have six complementarity defining regions (CDRs) (Janeway, see selection, in particular section 3-6). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chain, and not either alone, that determines the final antigen specificity. The prior art, however, did not establish that CDRs from structurally distinct antibody clones could be interchanged while retaining antigen binding in the absence of additional experimental testing to confirm that such modified antibodies retained functional activity. Indeed, amino acid variations in the CDRs of an antigen binding region can negatively impact binding activity (see, e.g. Piche-Nicholas et al, see in particular, Abstract; Colman, see entire document particularly Page 33, Col. 2; and Rudikoff et al, see Abstract). As such, artisans would not be able to readily predict which CDRs of structurally distinct anti-FGFR3 parental clones can be interchanged such that the resulting antibody retains the ability to bind to FGFR3.
A person of ordinary skill in the art at the time of filing would have had experience in antibody engineering, including library construction, mutagenesis, and screening techniques. Even at this high level of skill, however, the effect of combining CDRs from different anti-FGFR3 parental clones on antigen binding could not have been readily predicted without additional testing. In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement (MPEP 2164.06). Thus, the level of skill does not obviate the need for substantial experimentation across the full scope of the claimed genus. Indeed, the inventor’s own disclosure demonstrates that identifying functional antibodies required extensive screening. In the absence of guidance regarding the interchangeability of CDRs across different parental anti-FGFR3 clones, artisans would necessarily have to engage in undue trial-and-error experimentation to generate and test numerous CDR combinations encompassed by the claim scope to determine which retain binding to transferrin receptor. Claims 2, 3, 5, 6, 7, 40, and 42 incorporate limitations of claim 1 but do not cure the deficiencies of claim 1 and thus are also rejected.
Therefore, the specification is not enabling over the full scope of the claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 40, and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-16, 19-20, 25, 27, and 29 of copending Application No. 18879386 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims either anticipate or render obvious the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims recite an antibody drug conjugate comprising an anti-FGFR3 antibody or antigen-binding fragment thereof having the heavy chain CDRs of SEQ ID NOs: 1, 2, and 3 (corresponding to SEQ ID NOs: 5, 23, and 198 of the instant claims) and the light chain CDRs of SEQ ID NOs: 4, 5, and 6 (corresponding to SEQ ID NOs: 71, 93, and 114 of the instant claims) (co-pending claim 1). The anti-FGFR3 antibody can also be defined by a VH chain of SEQ ID NO: 7 and a VL chain of SEQ ID NO: 8, corresponding to SEQ ID NOs: 215 and 162, respectively, of the instant claims. Further recited is a pharmaceutical composition comprising the antibody drug conjugate and a pharmaceutically acceptable carrier (co-pending claim 15). In the preamble of instant claim 40, the phrase “for treating cancer or an inflammatory or immune disease” is a statement of intended use. Intended use statements do not distinguish over the prior art where the prior art teaches the same structure capable of performing the intended use (MPEP 2111.02). The wherein clauses of claim 42 appear to merely define the type of cancer by expression of a fusion protein. Since the preamble of claim 40 is a recitation of intended use, the wherein clauses of claim 42 do not carry patentable weight. As such, the composition of the co-pending claims can be used to treat a cancer, inflammatory, or immune disease in a subject.
Thus, the co-pending claims meet the limitations of instant claims 1-3, 40, and 42.
Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-16, 19-20, 25, 27, and 29 of copending Application No. 18879386, as applied to claims 1-3, 40, and 42 above, in view of Monnier et al, (Monnier, Philippe P., Robin J. Vigouroux, and Nardos G. Tassew Antibodies 2.2 (2013): 193-208), hereinafter Monnier.
This is a provisional nonstatutory double patenting rejection.
The teachings of the co-pending claims have been discussed above and differ from the instantly claimed invention in that it is not specifically taught the antigen-binding fragment is for example an scFv antibody.
However, Monnier teaches that scFv fragments retain the binding specificity of the parent antibody and offer several advantages compared to full-length mAbs, including having improved pharmacokinetic properties, such as better tissue penetration and rapid blood clearance, which may be beneficial in radiotherapy and diagnostic applications. For example, scFv fragments can penetrate more rapidly into tumors compared to an intact antibody (see Abstract and Introduction).
It would have been obvious to one of ordinary skill in the art to modify the anti-FGFR3 antigen-binding fragments disclosed by the co-pending claims such that it is a scFv fragment. One of ordinary skill in the art would have been motivated to do so in order to gain the advantage of improved pharmacokinetics, including tissue penetration and rapid blood clearance that can be beneficial in the treatment of cancer compared to intact antibodies. Therefore, one of ordinary skill in the art would expect that an anti-FGFR3 antibody that is an scFv fragment can more effectively treat a disease or disorder in a subject.
Conclusion
No claims are allowable.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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