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 .
DETAILED ACTION
The Amendment filed 5/25/2026 in response to Office Action of 2/25/2026, is acknowledged and has been entered. Claims 60-69, 71-73, and 75-81 are now pending. Claims 60, 62-63, 65-66, 71, and 76-77 are amended.
The 112(a) enablement and 112(d) rejections cited in Office Action 2/25/2026 are hereby withdrawn in view of amendments.
Claims 60-69, 71-73, and 75-81 are pending and currently under prosecution.
Priority
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Maintained Objections
Claim Objections
Claims 76 and 77 remain objected to under 37 CFR 1.75 as being a substantial duplicate of claims 71 and 72, respectively. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claims 71 and 72 is drawn to a method of treatment comprising administering the antibody or antigen-binding fragment of claim 60. Claims 76 and 77 are drawn to the same methods of treatment drawn to the nucleic acid molecule that encodes the heavy chain of the antibody according to claim 60. Thus, they are drawn to the same methods of treatment comprising the administering the same agent.
Response to Arguments
Applicant argues Claims 71 and 72 depend, either directly or indirectly, from claim 60, while claims 76 and 77 depend, either directly or indirectly, from claim 67. Applicant argues that claim 60 is directed to an antibody or antigen-binding fragment thereof (a protein), claim 67 is directed to a nucleic acid molecule encoding a heavy chain of the antibody or the antigen-binding fragment thereof. Applicant argues that that administering a nucleic acid to a subject is significantly different from administering an antibody.
Applicant’s arguments have been considered but are not persuasive. As noted in the objection, “When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).” The nucleic acid molecule encodes the heavy chain antibody of claim 60, thus are the same methods of treatment comprising administering the same agent.
New Objection
Claims 60, 62-63, 65-66, 71, and 76-77 are objected to because of the following informalities: The amendments are in a lighter color than black, please correct. Appropriate correction is required.
Claims 60 is objected to because of the following informalities:
Lines 5 and 13 recites “SEQID” – a space between SEQ and ID is needed
Line 9 recites “SEQTD”
Appropriate correction is required.
Maintained Rejection
(Arguments Addressed)
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 60-69, 71-73, and 75-81 remain 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an antibody or antigen-binding fragment thereof capable of specifically recognizing TrkA, wherein the antibody comprises a CDR sequence selected from the instantly claimed sequences. Thus, the written description is directed to the following:
the antibody, comprises “a” CDR sequences selected from the following; the claim as written is directed to an antibody comprising any single CDR of any heavy or light chain variable region to be used together;
the claim does not specify that any of the indicated heavy chain variable regions have to be used with any light chain variable regions.
the claim recites any antigen binding fragment without being drawn to any of the instantly claimed CDRs. The claim recites that the “antibody” comprises a CDR sequence.
The instant specification discloses full and specific sequences of heavy chain and light chain CDRs that are used together [see at least pg 16]. However, does not disclose the use of an antibody fragment, and does not disclose does not disclose any representative variants of the antibody that recognizes TrkA with less than 100% SEQ ID Nos.
By the time of the filing of the instant application, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4.
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Epitope Mapping, Biodrugs 2007; 21 (3): 145-156 page 146 section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence and length of VH-CDR3.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al., Benchmarking B cell epitope prediction: Underperformance of existing methods, Protein Science (2005), 14:246–248 pg. 246) . 3D structural analyses of antibody-epitope binding highlighting that the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al.,3D-Epitope-Explorer (3DEX): Localization of Conformational Epitopes within Three-Dimensional Structures of Proteins, Wiley Interscience, 2005 42–44, 60596, page 879).
Furthermore, changes in amino acid structures, particularly in CDR regions, can have impacts on antigen binding that are unpredictable. Rabia et al (Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility. Biochemical engineering journal, 137, 365–374, 2018) and Vajdos et al (Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis. Journal of molecular biology, 320(2), 415–428, 2022) teaches that changes to CDRs are unpredictable in terms of affinity, specificity, and solubility, (see Rabia whole documents), and teaches that even minute changes to the CDR region can impact binding affinities. (see Figure 2, effects of CDR mutations on binding affinity), respectively. Rudikoff et al (Single amino acid substitution altering antigen-binding specificity. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1979-83) teaches that single amino acid substitutions alter antigen-binding specificity. [Abstract] L stly, Herold et al (Sci Rep. 2017 Sep 25;7(1):12276) teaches and demonstrates that single and double mutations in exemplary antibodies, and found that single point mutations in the VH CDR region can completely abolish antigen binding. [see pg 8]
The structure activity relationship of the CDR antigen binding region that recognizes TrKA is not known and the binding epitopes cannot be predicted based on the antibody sequences. Walsh et al (A tale of two TrkA inhibitor trials: same target, divergent results. Osteoarthritis Cartilage. 2019;27(11):1575-1577) teaches the challenges of targeting TrkA. Walsh teaches and that although it is a promising therapeutic target, there needs to be more biologic insight into the mechanisms of the agents, and due to pharmacological differences no two agents can produce the same result. [whole document]
To provide adequate written description and evidence of possession of the claimed composition antibody genus, the instant specification can structurally describe representative antibodies or antigen binding fragments, that function to recognize TrkA and treating functions as claimed, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for antibodies that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The TrkA antigen provides no information about the structure of an antibody inhibits it.
Applicants have not established any reasonable structure-function correlation with regards to the sequences of the claimed antibody that can be altered and still maintain function. Therefore, one could not readily envision members of the broadly claimed genus.
Given the lack of representative examples to support the full scope of the claimed antibodies that inhibit one or more activities of TrkA, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs of the antibodies that function as claimed, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Response to Arguments
Applicant amended claims to remove “95% identity”. Applicant did not provide any further arguments. However, Applicant did not address parts (1) “the antibody comprises a CDR sequence, (2) the claim does not specify that any of the indicated heavy chain variable regions have to be used with any light chain variable regions, and (3) recites the use of any antigen binding fragment without being drawn to any of the instantly claimed CDRs. The claim as written is directed to the antibody comprising any one of the full indicated sets of CDRs. Therefore, rejection is maintained.
Claims 76 and 77 remain 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 treatment of pain comprising administering the claimed nucleic acid that encodes both a heavy chain and a light chain, does not reasonably provide enablement for treatment of pain comprising administering a nucleic acid that encodes only a heavy chain of the claimed antibody. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
BREADTH OF THE CLAIMS: The claims are drawn to methods of treatment comprising the nucleic acid molecule according to claim 67. Claim 67 is drawn to a nucleic acid molecule wherein the nucleic acid molecule encodes a heavy chain of the antibody or the antigen-binding fragment thereof of claim 60.
PRESENCE OR ABSENCE OF EXAMPLES: The instant specification discloses the uses and production of antibodies that recognized TrkA with both a heavy chain and light chains. There is no example use of a nucleic acid encoding only the heavy chain of the antibody.
STATE OF THE ART: It is well known in the art that full structures of antibodies are needed for function and that any changes in amino acid structures can have impacts on antigen binding that are unpredictable. Rabia et al (Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility. Biochemical engineering journal, 137, 365–374, 2018) and Vajdos et al (Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis. Journal of molecular biology, 320(2), 415–428, 2022) both teach that changes to the structure unpredictable in terms of affinity, specificity, and solubility, (see Rabia whole documents), and teaches that even minute changes to the CDR region can impact binding affinities. (see Figure 2, effects of CDR mutations on binding affinity), respectively. Thus, without knowing the complete structure of the antibody, it does not provide any support that the antibody will be have the same function properties.
PREDICITABILITY: The specification lacks the critical steps necessary in presenting some type of predictable response in a population of hosts deemed necessary to treat all the claimed disorders comprising administering a nucleic acid that only encodes the heavy chain of the antibody. There is no evidence in the instant application or the art that as noted in the prior that would function as claimed. demonstrate that a drug that treats a disease or disorder, including cancer, would prevent its onset in subjects as claimed. Thus, considering the high level of skill in the art, the state of the art, the level of predictability, and the guidance and examples provided, the experimentation required to enable the full scope of the claimed invention would not be reasonable.
QUANTITY OF EXPERIMENTATION: Undue experimentation would be required to determine claimed agent is administered to which population of subjects could treat as claimed. MPEP 2164.01 recites that “The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976)”. The experimentation needed to practice this method is undue and unreasonable as it requires determining whether the claimed nucleic acid encoding only the heavy chain treats as claimed. A person skilled in the art will not be able to use the invention without undue experimentation. (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988))
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Response to Arguments
Applicant amended claims 76 and 77 to recite only treating or preventing pain disorders. However, did not address the whole scope of the rejection, which is “does not reasonably provide enablement for treatment of pain comprising administering a nucleic acid that encodes only a heavy chain of the claimed antibody.” Therefore, rejection is maintained.
Maintained Rejection
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 60-69, 71-73, 75-81 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-48, 50, 52 and 53 of copending Application No. 17/911,571 (reference application, recently allowed 5/12/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending application is drawn to an antibody or antigen-binding fragment that recognizes TrkA, in which the antibody comprises the instantly claimed sequences. The co-pending application also recites methods of treatment comprising administering the instantly claimed antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
No argument is presented for this double patent rejection. Rejection is maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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 SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
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