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 Group I in the reply filed on 05/11/2026 is acknowledged. Claims 1-6 and 29 read on the elected invention.
Claims 1-8, 10-12, 15-16, 19-20, 23-25, and 28-30 are pending.
Claims 7-8, 10-12, 15-16, 19-20, 23-25, 28, and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-6 and 29 are pending and are currently under consideration. Regarding claim 3, SEQ ID 158 was searched and examined as it corresponded to applicant’s elected CDRs and VH/VL domains.
Information Disclosure Statement
The IDS filed 01/03/2024 contained two references that were not considered. CN 108220247 was not considered because the document was in Chinese including the abstract. Also, Nannini et al. from November of 2016 was not considered as it was not found in the file.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 33, line 21 and page 34, line 11). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The disclosure is objected to because of the following informalities: The specification filed 09/15/2023 is objected on page 57, line 22 and page 44, line 30 for recitation of an amino acid sequence in the absence of a sequence identifier. See 37 CFR 1.821(c). 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.
Drawings
Figures 6D and 8A are objected to for recitation of amino acid sequences in the absence of a sequence identifier. See 37 CFR 1.821(c). 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.
Claim Objections
Claims 1-3 are objected to for reference to non-elected subject matter. Claim 1 includes items (ii) through (xv) which is non-elected and Claim 2 recites items (ii) through (viii) which is non-elected. Claim 3 includes items (ii) through (viii) which are non-elected. See paragraphs 5-6 of the lack of unity restriction mailed 03/11/2026. Applicant is requested to cancel the non-elected subject matter.
Claim 3 is further objected to for reciting “or a variant thereof at least 80% sequence identity thereto” which is grammatically unclear. Applicants may wish to amend the claims to
“or a variant thereof with at least 80% sequence identity thereto”.
Claim Rejections - 35 USC § 112
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 5-6 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 5-6 recite the limitation "fragment thereof" in Claim 4. There is insufficient antecedent basis for this limitation in the claim.
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 1-6 and 29 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. This is a Written Description rejection.
The claims are broadly drawn to a binding domain that binds to CD160 wherein the structure is initially defined by complementary determining regions (SEQ IDs 1-6). But Claim 1 also includes alternative CDR structures wherein “one or more of the CDRs comprises one, two or three amino acid mutations”.
The specification teaches [0211] that it may be possible to introduce one or more mutations (substitutions, additions or deletions) into each CDR without negatively affecting CD160-binding activity. The broadest reasonable interpretation is that any or all 6 CDRs may each comprise up to 3 mutations which could be any one substitution, addition, or deletion or comprise all three types of mutations. Thus, in addition to the 6 defined CDRs, applicants are also claiming a genus of structural binding elements with the functional properties of binding to CD160.
A skilled artisan would understand that a conventional antibody heavy chain (HC) comprises a heavy chain variable region (VH) comprising HCDR1-3, and a light chain (LC) comprises a light chain variable region (VL) comprising LCDR1-3. Therefore, the claim(s) encompass a genus of heavy and/or light chain variable regions comprising variability in the heavy and/or light chain variable regions which are claimed as having the function of specifically binding to CD160 antigen. In this case, the variability in sequence identity occurs in the CDRs, the domains that are critical for the antibody binding to its target, and one of ordinary skill in the art would understand that such variability would result in unpredictable binding characteristics with no reasonable expectation of maintaining CD160 antigen binding. Additionally, the instant disclosure does not 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.
At the time of filing, antibody functionality was 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 substitutions, deletions, and additions 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 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, 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]. Thus, incorporating mutations to the complete six 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 nor envisage the breadth of all of the possible structurally unrelated CDR combinations that would still possess the required function(s). Thus, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. Thus, the art demonstrates that the antibody structure correlated with its antigen-binding function is six defined CDRs, and the position of each CDR.
Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant and tied to function, the claiming of up to 3 mutations in any or all of the CDRs is insufficient to describe the large genus. And while it may be possible to screen for variants that retain antigen binding, it is respectfully submitted that the number of possible variants permitted by the claimed language does not allow the skilled artisan to envisage those variants which would retain the required function. The ability of the claimed antibody to bind to its antigen is an essential feature of the claimed invention; therefore, the skilled artisan would need to identify functional variants of the antibody in order to make and use the invention. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe and enable the genus as broadly claimed.
Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991) clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of mutated CDR domains, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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