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, filed on 7/13/2026, is acknowledged.
Claim 8 is cancelled.
Claims 1-7 and 9-19 are currently pending.
Claim 1 is an independent claim
Election/Restrictions
Applicants’ election without traverse of Group I, claims 1-7, 9, 13, and 15, directed to an antibody that specifically binds to FGFR2IIIb; and the Species of FWB1914 and an IgG isotype, filed on 7/13/2026, is acknowledged.
Claims 10-12, 14, and 16-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or Species.
Claims 1-7, 9, 13, and 15 are under examination as directed to the anti-FGFR2IIIb antibody species FWB1914.
Priority
Applicant’s claim for the benefit of a prior-filed China Patent Application No. 202011600351.8 filed on December 29, 2020, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/18/2023 and 2/25/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties.
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 specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Specifically, amino acid sequences are disclosed in the specification in Tables 5, 6, and ¶[0033]-[0036] without the corresponding sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
Claims 1-7, 9, 13, and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It is apparent that the hybridomas that produce the FWB1904, FWB1905, FWB1906, FWB1907, FWB1908, FWB 1910, FWB1911, FWB1912, FWB1913, FWB1914, FWB1915, FWB1916, FWB1918, FWB1919, FWB1920, FWB1921, FWB1922, FWB1923, FWB1924 and FWB1925 antibodies are required to practice the claimed invention. As a required element, it must be known and readily available to the public or obtainable by a repeatable method set forth in the specification. If it is not so obtainable or available, the enablement requirements of 35 USC 112, a deposit of the hybridoma, which produces this antibody, may satisfy first paragraph. See 37 CFR 1.801-1.809.
If the deposit has been made under the terms of the Budapest Treaty, an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the hybridoma has been deposited under the Budapest Treaty and that the hybridoma will be irrevocably and without restriction or condition released to the public upon the issuance of a patent would satisfy the deposit requirement made herein. See 37 CFR 1.808. Further, the record must be clear that the deposit will be maintained in a public depository for a period of 30 years after the date of deposit or 5 years after the last request for a sample or for the enforceable life of the patent whichever is longer. See 37 CFR 1.806. If the deposit has not been made under the Budapest treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature must be made, stating that the deposit has been made at an acceptable depository and that the criteria set forth in 37 CFR 1.801-1.809, have been met.
If the deposit was made after the effective filing date of the application for a patent in the United States, a verified statement is required from a person in a position to corroborate that the hybridoma described in the specification as filed are the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant’s possession at the time the application was filed.
Claims 1, 3, 5, 7, 9, 13, and 15 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 antibody structures of the clones FWB1904, FWB1905, FWB1906, FWB1907, FWB1908, FWB 1910, FWB1911, FWB1912, FWB1913, FWB1914, FWB1915, FWB1916, FWB1918, FWB1919, FWB1920, FWB1921, FWB1922, FWB1923, FWB1924 and FWB1925, as defined by their amino acid sequences especially in the CDR regions critical for antigen binding with the function of “binds to FGFR2IIIb”, does not reasonably provide enablement for a broad genus of antibodies with a partial structure at best and the function of “binds to FGFR2IIIb”. 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 and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
Breadth of claims and nature of invention:
Claims 1, 3, 5, 7, 9, 13, and 15 encompass a broad genus of antibodies or antigen binding fragments thereof with a partial structure at best with the function of “binds to FGFR2IIIb”.
For example, instant claim 1 recites a broad genus of antibodies with the CDRs of the recited antibody clones with up to 20% variation in the CDR regions, all with the function of “binds to FGFR2IIIb”. The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula:
N
!
*
19
A
N
-
A
!
A
!
Where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. For the elected species of antibody clone (FWB1914), which comprises 54 residues in length of the CDR regions with 10 (54*0.2) allowed substitutions, there would be
54
!
*
19
(
10
)
54
-
10
!
10
!
Which is approximately 5.98x1025 variants of this clone alone, all with the function of “binds to FGFR2IIIb”.
The specification discloses specific antibody structures that specifically bind to FGFR2IIIb (Tables 1-5).
Amount of direction and existence of working examples:
The specification discloses the anti-FGFR2IIIb antibody clones FWB1904, FWB1905, FWB1906, FWB1907, FWB1908, FWB 1910, FWB1911, FWB1912, FWB1913, FWB1914, FWB1915, FWB1916, FWB1918, FWB1919, FWB1920, FWB1921, FWB1922, FWB1923, FWB1924 and FWB1925 all with the function of “binds to FGFR2IIIb” (Tables 1-5).
Level of predictability, state of prior art, and quantity of experimentation needed:
The claims are directed to antibodies or binding fragments thereof with a partial structure at best all with the function of “binds to FGFR2IIIb”, which includes broad genera of millions to billions of different structures with the recited function.
However, the specification did not give the skilled in the art enough information to choose candidate antigen binding structures from the vast number of options of millions of candidates, and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
The specification discloses 20 different anti-FGFR2IIIb antibody structures with the function of “binds to FGFR2IIIb”.
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. This decision reaffirmed the prior decision made by the Federal District Court in Amgen Inc. v. Sanofi, Aventisub LLC., 987 F.3d 1080 (Fed. Cir. 2021).
The Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id.
The specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art. For example, "it may suffice to give an example (or a few examples) if the specification also discloses some general quality … running through the class that gives it a peculiar fitness for the particular purpose" and "disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset." Id. at 611 (internal quotations omitted). However, the Supreme Court found that Amgen failed to enable all that it claimed, even if allowing for a reasonable degree of experimentation. Id. at 613; see also Baxalta Inc. v Genentech, Inc., 81 F.4th 1362, 1367, 2023 USPQ2d 1103 (Fed. Cir. 2023) ("[t]he facts of this case are more analogous to—and are, in fact, indistinguishable from—those in Amgen. We do not interpret Amgen to have disturbed our prior enablement case law, including Wands and its factors."). Moreover, "[w]e see no meaningful difference between Wands' ‘undue experimentation’ and Amgen's ‘[un]reasonable experimentation’ standards. Id. at footnote 4. See also Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024), which explains that regardless of the technology the Wands factors should be used when assessing enablement.
However, while the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class which included "a ‘vast’ number of additional antibodies" that Amgen had not described by their amino acid sequences. Id. at 613. The Court found that Amgen sought to monopolize an entire class by their function, even though that class was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. Id. at 613.
In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit explicitly applied the Wands factors to assess whether the specification of Amgen’s patent provided sufficient enablement, for purposes of 35 U.S.C. 112(a), to make and use the full scope of the claimed invention. The court 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. See also the following cases across various technology areas: McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 2020 USPQ2d 10550 (Fed. Cir. 2020); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 107 USPQ2d 1273 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 2019 USPQ2d 415844 (Fed. Cir. 2019).
Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims.
This case is akin to the issue in Amgen Inc. v. Sanofi, Aventisub LLC, in which the court 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. Sanofi-Aventisub at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a ‘vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure.
In the instant case, the claims are directed to a broad class of antibodies with a partial structure at best and the function of “binds to FGFR2IIIb”, which includes antibodies with variations in the CDR regions critical for antigen binding.
The instant claims are directed to classes of polypeptides that include “a ‘vast’ number” of additional structures (i.e., amino acid sequences of all of the CDR regions that are necessary for antigen binding) in which the instant specification fails to describe. It would be necessary to first generate and then screen each candidate agent to determine whether or not it met the function limitations of “binds to FGFR2IIIb”. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
The instant specification does not disclose any common structural feature delineating which other antibody structures would have the function of “binds to FGFR2IIIb”. The only structure-function relationship guidance the specification provides is to disclose individual examples of anti-FGFR2IIIb antibody structures with this function.
Additionally, the instant application encompasses (but does not exemplify) fragments and CDRs modification of up to 20% (deletion/addition/substitution) to the claimed CDRs (claims 1, 3, 5, 7, 9, 13, 15). There is no teaching identifying what amino acids can be varied within the VH-CDRs and/or VL-CDRs antibody regions and still retain the function of binding FGFR2IIIb. Brown et al. (J. Immuno. 1996 May, 3285-91 at 3290 and Tables 1 and 2) describes how a one amino acid change in the VH CDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region. Vajdos et al. (J. Mol. Biol. 2002, Jul 5, 320(2):415-28 at 416) teach that 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. 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. The scope of the claims encompasses antibodies with VH or VL that encompass variation (addition, deletion, substitution) in their CDRs. The prior art discloses that 6 CDRs as being essential structure of antibody's binding site, and thus when intact, would provide enough structure to define the antibody's binding site (structure/function correlation) e.g., where amino acid substitutions can be made so as to change (e.g., 6CDR's) or retain (e.g., constant or variable framework) antigen binding. Neither the prior art nor applicant's disclosure defines sufficient representative antibodies and/or sufficient structure/function correlation between modifying the VLCDRs or VHCDRs regions of the disclosed antibody and the retention of a specific binding antibody that binds FGFR2IIIb to satisfy the enablement requirement for the claims.
Regarding the amino acid substations in variable regions (claims 3 and 5), one skilled in the art would have recognized challenge and trade-offs once it is applied in antibody. Rabia et al. (Biochem Eng J. 2018 September 15; 137: 365-374) states that to optimize antibody properties (affinity, specificity, stability, solubility and effector functions) with amino acid substitutions is challenging and there is always trade-off. Rabia et al. further states that an outstanding challenge in the field is that optimizing properties such as antibody affinity can lead to defects in other properties such as antibody stability, specificity and solubility. The resulting trade-offs between improvements in some antibody properties and reductions in others highlight that they are often interdependent and cannot be easily separated (Introduction). Rabia et al. further state given that the maximal chemical diversity of antibody CDRs is unimaginably large (>1078 antibody variants based on 20 different amino acids at ~60 sites in the CDRs), it is extremely challenging to define the sequence determinants of antibody specificity (para 2).
The instant claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the antibody structures they elected to disclose and that “[u]nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10.
Applicant is relying upon certain biological activities such as inhibitory antibodies or specific FGFR2IIIb binding antibodies and a limited number of species with defined structures (e.g. amino acid sequences) to support an entire genus of diverse and structurally unrelated antibody structures. Yet the instant specification does not provide sufficient guidance and directions as to the structural features of the polypeptide structures and the correlation between the structure and the desired antigen binding and inhibitory function.
The Supreme Court’s 2023 decision in Amgen v. Sanofi, which mainly involves the enablement requirement, states that “where a patentee purports to invent an entire genus, it must enable the entire genus”; “disclosing how to produce some antibodies that perform a specified function is not equivalent to disclosing how to produce all such antibodies – and it is the latter that petitioners claim as their invention”; S. Ct.
Additionally, in its recent decision in Baxalta Inc. v. Genentech, Inc., No. 2022-1461, 2023 WL 6135930 (Fed. Cir. Sept. 20, 2023) the Federal Circuit found the facts of this case to be "materially indistinguishable from those in Amgen." Baxalta, 2023 WL 6135930, at *4. According to the Federal Circuit, claim 1 covers "millions of potential candidate antibodies" (id.) that bind to Factor IX/IXa and increase the procoagulant activity of Factor IXa. The court, however, noted that the specification discloses the amino acid sequence of just 11 of those antibodies. And like the roadmap in the patents at issue in Amgen, "the '590 patent's roadmap simply directs skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the [11] antibodies they elected to disclose." (Id.) Missing from the specification, according to the Federal Circuit, was "'a quality common to every functional embodiment' ... that would allow a skilled artisan to predict which antibodies will perform the claimed functions" (id.; quoting Amgen Inc. v. Sanofi., 598 U.S. 594, 614 (2023)), such as a common structural or other feature that would allow the antibodies to perform the claimed functions, or an explanation as to why the 11 antibodies do so and others do not. (Baxalta, 2023 WL 6135930, at *4). And the Federal Circuit was not persuaded by Baxalta's argument that its disclosed hybridoma-and screening process "predictably and reliably generates new claimed antibodies every time it is performed" (id.), because "it is undisputed that to practice the full scope of the claimed invention, skilled artisans must make candidate antibodies and screen them to determine which ones perform the claimed functions." (Id.).
The specification does not reasonably provide enablement to make and use the invention of instant claims 1, 3, 5, 7, 9, 13, and 15. The specification does enable one with ordinary skill to make the antibody clone discussed supra.
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 limited working examples, 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.
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 1-7, 9, 13, and 15 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.
Claims 1-7, 9, 13, and 15 are indefinite in the recitation of “FWB1904, FWB1905, FWB1906, FWB1907, FWB1908, FWB 1910, FWB1911, FWB1912, FWB1913, FWB1914, FWB1915, FWB1916, FWB1918, FWB1919, FWB1920, FWB1921, FWB1922, FWB1923, FWB1924 and FWB1925” because their characteristics are not known. The use of "FWB1904, FWB1905, FWB1906, FWB1907, FWB1908, FWB 1910, FWB1911, FWB1912, FWB1913, FWB1914, FWB1915, FWB1916, FWB1918, FWB1919, FWB1920, FWB1921, FWB1922, FWB1923, FWB1924 and FWB1925" monoclonal antibodies as the sole means of identifying the claimed antibody and hybridoma renders the claim indefinite because "FWB1904, FWB1905, FWB1906, FWB1907, FWB1908, FWB 1910, FWB1911, FWB1912, FWB1913, FWB1914, FWB1915, FWB1916, FWB1918, FWB1919, FWB1920, FWB1921, FWB1922, FWB1923, FWB1924 and FWB1925" are merely laboratory designations which does not clearly define the claimed product, since different laboratories may use the same laboratory designation s to define completely distinct hybridomas or cell lines. It is suggested to use the specific antibody structures, defined by their amino acid sequences in the CDR regions critical for antigen binding, to overcome this rejection.
Claim 7 is additionally indefinite because the claim recites: “…wherein the antibody is a human antibody, a humanized antibody…”. The instant specification discloses that the instant claimed antibodies are human antibodies (¶[0002]): “…specifically human anti-FGFR2 antibody molecules…”. It is currently unclear how a human antibody can also be “humanized”, which is an antibody from a species other than human that has been modified to have reduced immunogenicity in humans.
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 1-7, 13, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18/699,062 (App ‘062). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘062 claims anti-FGFR2 antibodies comprising a heavy chain of SEQ ID NO: 12 (claim 4), which is 100% identical to instant SEQ ID NO: 179:
PNG
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134
610
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134
610
media_image1.png
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App ‘062 claims the anti-FGFR2 antibodies comprise a light chain of SEQ ID NO: 11 (claim 4), which is 100% identical to instant SEQ ID NO: 180:
PNG
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310
615
media_image2.png
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App ‘062 additionally claims the antibody is an IgG1 antibody (claim 3). Therefore, App ‘062 claims an anti-FGFR2 antibody comprising the heavy and light chain sequences of the elected species of antibody clone FWB1914, meeting the limitations of instant claims 1-6.
Regarding instant claim 7, App ‘062 claims an identical antibody structure to the instantly claimed invention. As discussed in the 35 U.S.C. § 112(b) rejection supra, the instantly claimed antibodies are human antibodies. Therefore, the antibody claimed by App ‘062 is considered to also inherently be a human antibody in absence of evidence to the contrary, meeting the claim limitations.
Regarding instant claim 13, App ‘062 claims pharmaceutical compositions comprising the antibody (claim 22), and methods of treating an FGFR2 expressing cancer comprising administration of the antibody/pharmaceutical compositions (claims 23 and 24), meeting the claim limitations.
Regarding instant claim 15, App ‘062 claims antibody drug conjugates comprising the antibody and a conjugated drug (claim
The instantly claimed invention is anticipated by App ‘062. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-7, 9, 13, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18/699,062 (App ‘062, supra) in view of Ahmad et al. (Clin Dev Immunol. 2012;2012:980250. doi: 10.1155/2012/980250. Epub 2012 Mar 15).
The invention encompassed by claims 1-7, 13, and 15 are anticipated by App ‘062, as discussed supra. App ‘062 does not claim the anti-FGFR2 antibodies in an scFv version (i.e., the limitations of instant claim 9).
Ahmad et al., in the same field of endeavor, teaches antibodies can be engineered in a single-chain format, or an scFv (pg. 2, Section 3): “An antibody in scFv (single chain fragment variable) (Figure 1) format consists of variable regions of heavy (VH) and light (VL) chains, which are joined together by a flexible peptide linker that can be easily expressed in functional form in E. coli, allowing protein engineering to improve the properties of scFv (single chain fragment variable) such as increase of affinity and alteration of specificity”
Ahmad et al. additionally teaches benefits of scFvs over full-length antibodies (pg. 6-7, Section 8): “An antibody in scFv (single-chain fragment variable) format retained the complete antigen-binding capability…The small antigen-binding molecule of scFv (single chain fragment variable) antibodies could offer several advantages over a whole antibody molecule in therapeutic applications [20, 22]. The smaller fragments allow these molecules to penetrate more rapidly and evenly to tumors and other tissue in comparison to the whole antibodies [20, 121]. As these fragments have more rapid clearance from blood, they can be coupled with drugs and radionuclides in order to result in low exposure of the healthy tissue [19, 122, 123]. Besides that, they also found that there was no uptake of the scFv (single-chain fragment variable) by the kidney and they could efficiently localize to the tumors…”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the anti-FGFR2 antibodies claimed by App ‘062 in view of Ahmad et al. to generate scFv versions of the claimed antibody structures, as Ahmad teaches the general structure of an scFv that can be applied to antibodies such as those claimed by App ‘062. One would be motivated to make this change for the purposes of generating scFv versions of anti-FGFR2 antibodies that have advantages over the full-length antibody, such as increased tissue penetration and low exposure of coupled drugs/radionucleotides to healthy tissue, as taught by Ahmad et al.
Therefore, the invention as a whole is a prima facie obvious variant of the invention claimed by App ‘062 in view of Ahmad et al., especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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