Status of the Claims
Claims 1, 6-13, 15-20, 23, 28, 61, and 65-73 are pending and examined herein.
Claims 2-5, 14, 21-22, 24-27, 29-60, and 62-64 are cancelled.
Claims 6-8, 12, 17, and 61 are amended.
Claims 65-73 are newly presented.
Applicant's election without traverse of Group I in the Response filed on 07/13/2026 is acknowledged.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claims 1 and 61 are objected to because of the following informalities:
Claim 1, line 6 – missing an article before “N-terminus”;
Claim 61, line 3 – “comprise” should be “comprises”;
Claim 61, lines 8 and 10 – missing an article before “N-terminus” (line 8) and “free state” (line 10).
Appropriate correction is required.
Claim Interpretation
The claims of the instant application all involve a “second binding moiety” having “an N-terminal truncation”. As an N-terminal truncation refers to the manner in which the second binding moiety was made, this constitutes a product-by-process limitation. According to MPEP § 2113, “If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” Furthermore, the N-terminal truncation is functionally non-limiting as the “original” or “non-truncated” second binding moiety is undefined.
It is noted that the linker limitation of claim 1 is optional, and as claim 15 does not further specify that it is required, the limitations of claim 15 and all claims that depend upon it are also considered optional.
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, 6-13, 15-20, 23, 28, 61, and 65-73 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. In the instant application, the breadth of the claims is not adequately supported by the specification. The claims recite “binding moieties” and “antibody moieties”, which include a vast number of diverse species. However, the specification describes co-binders consisting of dual VHH domains. Furthermore, of the described dual VHH domain co-binders, several are delineated by their target (Example 14), which does not constitute adequate description of the claimed “antibody moieties” (see MPEP § 2163(II)(A)(3)(a)).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 61 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Specifically, claim 61 is dependent on claim 1, as it recites “a control co-binder specifically binding to a target molecule of claim 1”. However, claim 61 later states that the second binding moiety does not comprise an N-terminal truncation. Therefore, claim 61 does not incorporate all limitations of claim 1 from which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Holliger et al.
Claims 1, 6, 8-9, and 15-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Holliger et al. (Proc. Natl. Acad. Sci. USA (1993), 90: 6444-6448; cited in IDS of 3/14/2024).
Regarding claims 1, 6, 8-9, and 15-20, Holliger discloses a co-binder comprising a VH domain and a VL domain that specifically recognize first and second target sites (p. 6444, col. 2, 1st ¶) connected via direct fusion to the N-terminus of the VL domain (p. 6446, col. 1, 2nd ¶: “we joined the C terminus of the VH domain directly to the N terminus of the VL domain”).
Roovers et al.
Claims 1, 7, 10-13, 15-18, 23, and 65-73 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Roovers et al. (Int. J. Cancer (2011), 129: 2013-2024; cited in IDS of 3/14/2024).
Regarding claims 1, 7, 10-13, 15-18 and 65-69, Roovers discloses a co-binder comprising a first VHH domain and a second VHH domain (Table 2: 7D12-9G8; p. 2016, col. 2, last ¶: “The biparatopic nanobody 7D12-9G8”) that specifically recognize non-overlapping first and second target sites (p. 2016, 1st ¶), connected via a linker through the N-terminus of the second binding moiety (p. 2022, col. 2, 1st ¶: “…N-terminus of 9G8…”). Additionally, Roovers discloses that the linker is a peptide linker that comprises (G4S)2 repeats (p. 2016, col. 2, 2nd ¶) and where X1-X2-X3 is G-G-G and connected to the N-terminally truncated second binding moiety (see below).
N-terminal sequence of 9G8:
(truncated 10 a.a.s in FR1 region)
C-terminal sequence of linker:
GGGSEVQLVESGGG
Construct:
(GGG = X1-X2-X3)
GGGSEVQLVESGGGLVQAGGSLRL
Regarding claim 23, Roover further discloses that the co-binder comprises a third binding moiety specifically recognizing a third target site (p. 2017, col. 2, last ¶ - p. 2018).
Regarding claims 70-73, Roover further discloses a library of the 7D12-9G8 co-binders wherein they differ from each other in the linker (p. 2017, 2nd ¶: “flexible linkers consisting of G4S repeats varying in length from 5 to 30 amino acids”) and screening the library by contacting it with a target molecule comprising the second target site to form complexes between the co-binders and the target molecule (Figure 4a) and identifying a co-binder that binds to the target with the desire affinity (p. 2017, 2nd ¶: “a linker of 10 amino acids was chosen as the optimal format for the anti-EGFR 7D12-9G8 biparatopic nanobody”).
Munter et al.
Claims 1, 7, 10-13, 15, 28, and 65-68 re rejected under 35 U.S.C. 102(a)(1) as being anticipated by Munter et al. (Int. J. Mol. Sci. (2018), 19: 403).
Regarding claims 1, 7, 10-13, 15, 28, and 65-68, Munter discloses a co-binder (Figure 1A, 2nd construct) that comprises first and second VHH domains that specifically recognize first and second non-overlapping target sites (CD20 and HER2 nanobodies) connected via the N-terminus of the second VHH H klasdjfH domain, connected by a peptide linker (long hinge lama linker), and the co-binder is a chimeric antigen receptor (p. 2, 4th ¶: nanoCAR).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Roovers et al., Yang et al., and Norihiro et al.
Claim 61 is rejected under 35 U.S.C. 103 as being unpatentable over Roovers et al. in view of Yang et al. (Appl. and Environ. Microbiol. (2013), 79(20): 6429-6438) and Norihiro (JP2021141861A). Roovers discloses all limitations of claim 1 as discussed previously. However, Roovers does not disclose a co-binder and a control co-binder that differ from one another in N-terminal truncation of the second binding moiety and having an increased binding affinity compared to the control.
Yang teaches that N-terminal truncation can be an advantageous method of fusion protein engineering that can increase the binding affinity of the truncated protein (abstract; Table 2). Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to apply the protein truncation method of Yang to the biparatopic nanobody construct of Roovers to yield a co-binder with increased affinity upon N-terminal truncation. There would have been a reasonable expectation of success in doing so, as Norihiro discloses that the N-terminus of antibody fragments can be altered within the framework 1 region to produce an antibody fragment with improved affinity, demonstrating that the N-terminal residues are not necessary for specific binding (abstract).
Conclusion
No claims are allowed.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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