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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 8/4/2025 is acknowledged.
Accordingly, claims 27, 28, 32-40 are withdrawn from consideration for being directed to non-elected subject matter. Claims 1, 2, 22-26, 29-31 are currently under examination.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/631,437 (now issued US.114,144,78), filed on 01/15/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/28/2023 has been considered by the examiner.
Drawings
The drawings were received on 9/26/2022. These drawings are acceptable.
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 deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Specifically, the amino acid sequence in Fig.12 does not have sequence identifier.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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 Objections
Claim 1 is objected to because of the following informalities: Claim 1 recites abbreviation “CL” and “CH1.” It is suggested to spell out both term entirely when first mentioned in a claim. Appropriate correction is required.
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 25, 26, 29-31 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 25, the recitation of “wherein the C-terminus of the antigen-binding part is fused to a hinge region and further immunoglobulin constant domains” renders the claim indefinite because it is unclear where the hinge region and further immunoglobulin constant domains is fused to in the context of the heavy chain variable domain (VH) antibody (scVHAb) having the structure of VH-L1-CL-L2-CH1. Claim 1 recites the antigen-binding part consists of a VH domain, and the scVHAb comprises VH, CL and CH1 in the following order VH-L1-CL-L2-CH1, so when the additional constant domain is fused to said VH, does it immediately following the VH (before L1), or following CH1 at the C terminus end? There is no description in the specification that clarifies this indefiniteness.
Claim 26 is rejected for same reason because it depends on claim 25 but does not remedy the indefiniteness of claim 25.
Regarding claim 29, the recitation of “said repertoire is obtainable by cloning the genes encoding the antibodies from B cells or by secreting the antibodies by a variety of mammalian plasmacytes” renders the claim indefinite because it is unclear whether “cloning the genes encoding the antibodies” are referring to cloning genes from naturally occurring antibodies to make the scVHAb recited in claim 1, or cloning genes that encodes a diversity VH domain of the repertoire.
Dependent claims 30-31 are rejected for same reason because they depend on claim 29 but does not remedy the indefiniteness of claim 29.
Prior art:
All claims are free of the prior art because the totality of the prior art does not provide a substantial evidence to teach, suggest or provide one of ordinary skilled in the art a motivation to arrive at the claimed scVHAb having the configuration of VH-L1-CL-L2-CH1, wherein L1 is optional, L1 and L2 are each, independently, peptide linkers; and L2 is a peptidic linker with a length of 25-50 amino acids having a sequence consisting of glycine and serine in any combination; and wherein CL is paired with CH1 through beta-sheet contact and forming CL/CH1 dimer.
Bacac (WO2017/055388, IDS) teaches engineering bispecific antigen binding molecules for T cell activation, wherein the components of said T cell activating bispecific antigen binding molecule can be fused to each other in a variety of configuration (page 43, lines 19-20), including VL-CH1-CH2-CH3-(CH4), VH-CH1-CH2-CH3-(CH4), VH-CH1-VL-CH1-CH2-CH3-(CH4)…(page 48, line 10-33, and various exemplary configuration illustrated in Figure 1 A-Z). Gauthier (WO2016207272, IDS) teaches engineering multi-specific antigen binding proteins that comprises single peptide chains in different domain arrangements of bispecific protein (Figure 2A-2E, and page 19, lines 33-35), the configuration including VH-CH1-Fc domain-VH-CK…(page 36-37, Table 1). Both reference represents the state of art regarding generating multi-specific or bispecific antibodies in different domain arrangement and configuration. However, they do not teach, or provide motivation to arrive at the specific configuration claimed in claim 1 of present application, a scVHAb having the configuration of VH-L1-CL-L2-CH1, wherein L1 is optional, L1 and L2 are each, independently, peptide linkers; and L2 is a peptidic linker with a length of 25-50 amino acids having a sequence consisting of glycine and serine in any combination; and wherein CL is paired with CH1 through beta-sheet contact and forming CL/CH1 dimer.
Allowable Subject Matter
Claim 1, 2 and 22-24 would be allowable if rewritten to overcome the objection as discussed above.
Claims 25, 26, 29-31 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637