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 .
Claim Interpretation
The specification defines “antibody” in [0034] as referring “to immunoglobulins with full length heavy chains and light chains.”
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 deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See [0058], line 3l; [0062] line 5; [0072], line3.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
Specification
It is noted that “EFTAE” is apparently being used as a name in the specification not an amino acid sequence per se (e.g., [0027]).
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: RITUXIMAB-NKG2D LIGAND DOMAIN MUTANT FUSION PROTEIN AND METHOD OF TREATING CD20-POSITIVE CANCER
The use of the term “MicAbody”, “convertibleCAR”, “Alexa Fluor” (see e.g., [0022]-[0023]), and “Fortebio” ([0059]), each of which is a trade name or a mark used in commerce, 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.
Applicant is encouraged to review the disclosure for additional trade names or marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See [0056]. 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: [0093], last line, It appears “opportunity rearm” is missing “to” between the words.
Appropriate correction is required.
Claim Objections
Claim 11 is objected to because of the following informalities: line 3 recites “variable region sequences” comprising SEQ ID NO:1, however, a heavy chain typically only has one variable chain sequence. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 14 and 20 is 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.
Claim 14 is indefinite because the metes and bounds of the claim are not clear. It is unclear if the host cell is intended to be “in vitro” or “ex vivo” or includes “in vivo” cells. If Applicant intends that the host cell is not in an animal (i.e., is not in vivo), then a term such as “isolated” before “host cell” would obviate this rejection (see [0052], second sentence, for support). If Applicant intends that host cells in vivo are included, then this claim would be subject to a rejection under 35 USC 112, first paragraph, for lack of enablement for transgenic animals or gene therapy. Note that if the latter is the case, a rejection under 35 USC 112, first paragraph, would not be considered a new rejection and would not preclude the next Office action from being made final since the issue is here raised.
Claim 20 is indefinite because it depends from a canceled claim (claim 18). As a result, it cannot be further examined.
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 1, 10-12, 14, 16, 17 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-26, 28, 29, 33, 34 and 36 of copending Application No. 18/568,405 (‘405) in view of US Patent 11,324,744 B2 (Jones) and WO 2017/024131 A1 (WO ‘131, cited in the IDS filed 0/01/2026).
The instant claim 1 is drawn to an antibody fusion comprising heavy chains comprising the variable region of SEQ ID NO:1 and light chains comprising the variable region of SEQ ID NO:8, wherein the light chains are fused at the C-terminus to an A1-A2 domain of SEQ ID NO:11. Claims 1-12, 14 and 16 are drawn to nucleic acids encoding the antibody fusion, a vector comprising the at least the nucleic acid encoding the antibody light chain-A1-A2 domain fusion, a host cell comprising the vector and a method of making the antibody fusion by culturing the host cell. Claim 21 is drawn to treatment of a CD20-positive cancer by administration of the antibody-fusion and mammalian cell comprising the chimeric antigen receptor comprising SEQ ID NO:15.
Application 18/568,405 claims an antibody fusion protein comprising an anino acid sequence of SEQ ID NO:30, wherein residues at positions 40 and 54 are glutamine (claims 24-26). This is the same as SEQ ID NO:11 (claim 28). This sequence is identical to instant SEQ ID NO:11. Claims 29, 33, 34 and 36, depend respectively from claims 24-26 and 28 and limit the fusion of the domain to the antibody light chain. This copending application does not claim wherein the antibody had the variable heavy and light chains of SEQ ID NO:1 and 8, respectively, or an encoding nucleic acid thereof or method of treatment.
Jones teaches CD20 inhibitory antibodies for use in treatment of B-cell cancers (col. 1, lines 36-41). The variable light chain may be SEQ ID NO:9 (col. 9, lines 13-15), which is the same as instant SEQ ID NO:8. The variable heavy chain may be from of SEQ ID NO:62 (col. 18, lines 37-38), which comprises instant SEQ ID NO:1.
WO 2017/024131 A1 teaches a mutant NKG2D comprising the sequence of SEQ ID NO:80 (end of [0096]), which is identical to instant SEQ ID NO:15, that does not bind natural ULBP2 ligand but does bind an orthogonal mutant ([0110]). The ligand may be an engineered A1-A1 (α1- α2) domain of the ULBP protein [0098]. It may be fused to an antibody and produced by recombinant means, i.e., the encoding nucleic acid is cloned into an expression vector and when it encodes a heavy chain fusion, then a nucleic acid encoding the light chain is co-expressed in an HEK293 host cell ([0161]). It is also taught wherein the receptor is in the form of a chimeric antigen receptor that is expressed on a T cell to make a non-natural NKG2D CAR-T cell that was selectively activated by the mutant α1- α2 domain-antibody fusion and not the natural ligand ([0118]). The only antibody fusion format explored was that with fusion on the heavy chain.
It would have been obvious wherein the A1-A1 (α1- α2) domain peptide of ‘405, which is inherently a mutant A1-A2 domain that would reasonably be expected to bind a selected non-natural NKG2D, was fused to an antibody for targeting to a cell for cell-killing, as with CD20 antibodies used in the treatment of B-cell cancers. As a result, it would have been obvious wherein the antibody was an anti-CD20 antibody, such as one comprising the variable heavy and light chains found in SEQ ID NO:62 and 9 of Jones. It would have been obvious to combine the fusion antibody with the non-natural NKG2D that bound it to further direct cell killing to the CD20-expressing cancer, i.e., B-cell cancers. Because WO ‘131 taught recombinant expression of the A1-A2 domain-antibody fusion, encoding nucleic acids would have been obvious, including wherein either the encoded heavy or light chain was linked to the A1-A2 domain as taught by WO ‘131 for the linkage to the heavy chain. To express the antibody, it would have been obvious to use methods well-known and routine in the art wherein the encoding nucleic acids were in one or two expression vectors and used to transfect a host cell for the expression. There would have been a reasonable expectation of successful recombinant formation of a functional CD20 binding antibody whether the ligand was fused to C-terminus of the heavy or light chain. It would have been obvious wherein the antibody fusion protein was in a kit comprised in at least one container.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claims 2-9, 22 and 23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
The specification states that the orthogonal ligand A1-A2 domain having the sequence of “SEQ ID NO:11 is based on the U2S3 ligand.” (see paragraph [0077] of the specification). However, it differs from U2S3 of the prior art by having Q at positions 40 and 54 instead of N in the original (see, e.g., Landgraf et al., BioRx, 2019, and Communic. Biol. 2020, both cited in the IDS filed 7/1/2024, Fig. 1C).
US Patent 12,145,976 B2 (from US 2019/03000594, cited in the IDS filed 7/1/24) is cumulative with Landgraf et al. 2019 (supra). While it teaches non-natural NKG2D ligands, the closest (SEQ ID NO:127) to instant SEQ ID NO:11 differs by the same 2 amino acids as Landgraf. SEQ ID NO:153 of the patent comprises instant NO:15-18 of the non-natural NKG2D CAR.
US 2025/0109178 teaches non-natural NKG2D CAR of SEQ ID NO:153 that comprises instant SEQ ID NO:15-18, but again has two amino acids different in the disclosed NKG2D mutant A1-A2 domain ligand (SEQ ID NO:127) compared to instant SEQ ID NO:11. Further, this reference is excepted under 102(a)(2) because it is by the same inventive entity and assignee of the instant application.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
September 3, 2026
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