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 .
Claims Status
Claim(s) 1-21 is/are currently pending.
The Amendment filed on 21Nov2025 in which claim(s) 17 is cancelled by Applicant is acknowledged.
Applicant’s election without traverse of Group I (claims 1-16 and 18) and further species election of (1) a VL of SEQ ID NO: 17 and (2) a VH of SEQ ID NO: 50 in the reply filed on 21Nov2025 is acknowledged.
Claim(s) 9-16 and 19-21 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 21Nov2025.
Claim(s) 1-8 and 18 is/are currently pending and presented for examination on the merits.
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., Invitrogen, Clontech, Kodak, Glaxco, Mallinckrodt Inc., Fisons Corp., Nektar, Alkermes, Mankind), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are 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 commercial marks.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 2 is/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.
Regarding claim 2, the phrase “(Fc)” is not defined in the terms preceding it. Thus, the phrase “(Fc)” renders the claim indefinite because it is unclear whether the limitation(s) in the parentheses are a part of the claimed invention. See MPEP 2173.05(d). Specifically, it is accepted in the art that an “immunoglobulin constant region” comprises CH1, hinge, CH2, and CH3 domains, whereas an “Fc” comprises only CH2 and CH3 domains. Therefore, it[[It]] is unclear if “Fc” is a limitation or merely provided as an example. To promote compact prosecution, the phrase “Fc” is not considered a limitation of the claim(s). This rejection may be overcome by amending claim 2 to delete “(Fc)”.
Claim Rejections - 35 USC § 112(a)
Claim(s) 1-8 and 18 is/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.
Claimed Invention
Claim(s) 1-8 and 18, are drawn to an antibody that binds FLRT3 antigen.
Breadth of Claims
The invention as disclosed in claim(s) 1 (and dependent claims 2-8 and 18) recite(s) “…a light chain variable region having at least 95%, 99%, or more sequence identity to SEQ ID NO: 17…”, and “…a heavy chain variable region having at least 95%, 99%, or more sequence identity to SEQ ID NO: 50…”. The claim(s) encompass a genus of heavy and/or light chain variable regions comprising variability (e.g., 95% identical) in both the heavy and/or light chain variable regions which are claimed as having the function of specifically binding to FLRT3 antigen. This means that the variability in sequence identity can also occur in the CDRs, the domains that are critical for the antibody binding to its target, which one of ordinary skill in the art would understand to result in unpredictable binding characteristics with no reasonable expectation of maintaining FLRT3 antigen binding. Additionally, the instant disclosure does not provide an adequate number of species of the claimed genus nor does the disclosure provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision what variation can occur to the light and heavy chains, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
The anti-FLRT3 antibody in the Applicant disclosure comprising a VL of SEQ ID NO: 17 and a VH of SEQ ID NO: 50, with 100% sequence identity in the CDR regions of the heavy and light chain variable regions represents the anti-FLRT3 antibody that the applicant was in possession of at the time of filing.
State of the Prior Art
At the time of filing, antibody functionality were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that mutation to CDRs is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
At the time of filing, US 2018/0002419 A1 (hereinafter “US419”) taught FLRT3 inhibitors were recognized in the art as a promising therapeutic for the treatment of neuropathic pain in a variety of diseases [e.g., title, abstract; ¶ 0001-0002]. US419 taught a single anti-FLRT3 antibody [e.g., ¶ 0045, 0053, 0081, 0088; example 2]. The prior art does not teach a known structure activity relationship for HCDR1-3 and LCDR1-3 in anti-FLRT3 antibody that would allow prediction of CDR residues that specifically bind to FLRT3 antigen.
Thus, making changes to the CDR sequence of an antibody sequence is a highly unpredictable process and one skilled in the art could not a priori make any predications regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required function(s).
Conclusion
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which CDR residues may be changed and still result in an antibody that binds FLRT3 antigen. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in an antibody antigen-binding domain are the minimal structure that binds to a target antigen. Specifically, Applicant claim(s) 1 would need to recite the VH and VL (e.g., comprising 6 CDRs) in the antibody that bind FLRT3 antigen, without variability in the CDR sequences thereof (e.g., HCDR1-3 and LCDR1-3). Dependent claims 2-8 and 18 can overcome this rejection by amending claim 1 as described above.
Free From the Prior Art
During the course of examination, the anti-FLRT3 antibody antigen binding domain comprising a VH/VL of SEQ ID NOs: 50/17 was searched independently (e.g., VH only, VL only) and in both orders (e.g., VH to VL, VL to VH), was found to nonobvious over the prior art. Briefly, a sequence search of the prior art returned no 100% matches to the instant claimed VH/VL pair (see closest prior art alignment below).
Alignment of anti-FLRT3 VH (SEQ ID NO: 50) with WO2025167991-A1 (Anti-IL-31RA antibody 1A1C6 VH region protein, SEQ ID: 42):
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Alignment of anti-FLRT3 VL (SEQ ID NO: 17) with WO2021246413-A1 (Anti-IGF-1 receptor humanized antibody VL mutant, SEQ ID 23):
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Alignment of anti-FLRT3 VH/VL (SEQ ID NO: 50/17) with WO2019232503-A1 (Anti-CD20/CD28 bispecific antibody, SEQ 11858):
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Alignment of anti-FLRT3 VL/VH (SEQ ID NO: 17/50) with WO2021173307-A1 (Anti-CD137 scfv-anti-CD28 scfv mutant C50S-Fc fusion, SEQ ID 500):
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Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643