DETAILED ACTION
Status of the Application
Claims 38, 65-76 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claim 38 and cancellation of claims 1, 34-37, 43, 48, 54, 60, 64 as submitted in a communication filed on 9/21/2026 is acknowledged.
Applicant’s election of Group III, claim 38, drawn to a method of producing a genetically modified eukaryotic cell with a nucleic acid encoding a meganuclease, as submitted in a communication filed on 9/21/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
New claims 65-76 are directed to the elected invention. Claims 38, 65-76 are at issue and will be examined to the extent they encompass the elected invention.
Specification
The first paragraph of the specification is objected to because it does not provide the current status of related applications (e.g., now abandoned, now US Patent No. X). Appropriate correction is required.
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 title refers to nucleic acids while the claims are directed to a method for producing a genetically modified eukaryotic cell. Appropriate correction is required.
Priority
Acknowledgment is made of a claim for domestic priority under 35 U.S.C. 119(e) to provisional application No. 62/297,445 filed on 02/19/2016, and 62/237,382 filed on 10/05/2015.
Acknowledgment is made of a claim for domestic priority under 35 U.S.C. 120 or 121 to US application No. 17/589,594 filed on 01/31/2022, 17/016,056 filed on 09/09/2020, and 15/766,290 filed on 04/05/2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/9/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings submitted on 8/2/2024 have been reviewed and are accepted by the Examiner for examination purposes.
Claim Objections
Claim 38 is objected to due to the recitation of “cleaves at a recognition sequence consisting of SEQ ID NO: 3”, “…binds to a…half-site of said recognition sequence..”, and “cleavage site in said…at said recognition sequence”. To enhance clarity, the term should be amended to recite “cleaves at a recognition site that consists of SEQ ID NO: 3 in a …gene”, “…binds to a…half-site of said recognition site..” and “cleavage site in said…at said recognition site”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 38, 65-76 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 pre-AIA the applicant regards as the invention.
Claim 38 (claims 65-76 dependent thereon) is indefinite in the recitation of “eukaryotic cell comprising an exogenous sequence of interest inserted into a chromosome ….T cell receptor alpha constant region gene….wherein said sequence of interest is inserted into said chromosome…” for the following reasons. As known in the art, a nucleotide sequence is a graphical representation of the order in which nucleotides are arranged in a polynucleotide. Therefore, while a polynucleotide can be inserted into the chromosome of a cell, a cell cannot have a sequence or have a sequence inserted into its chromosome. In addition, the term “T cell receptor alpha constant region gene” is unclear because one cannot determine what an alpha constant region of a gene is. If the intended limitation is a method for producing a genetically modified eukaryotic cell that comprises an exogenous nucleic acid of interested inserted into a chromosome of said eukaryotic cell, wherein said method requires transfecting said eukaryotic cell with a polynucleotide that comprises said exogenous nucleic acid, the claim should be amended accordingly. No patentable weight will be given to the term “alpha constant region”. For examination purposes, it will be assumed that the engineered meganuclease binds and cleaves at a recognition site that consists of SEQ ID NO: 3 in a T cell receptor gene. Correction is required.
Claim 65 is indefinite in the recitation of “said sequence of interest is inserted at said cleavage site by homologous recombination” for the following reasons. As indicated above, a nucleotide sequence is a graphical representation of the order in which nucleotides are arranged in a polynucleotide. Therefore, while a polynucleotide can be inserted into the chromosome of a cell, a cell cannot have a sequence or have a sequence inserted into its chromosome. If the intended limitation is the insertion of an exogenous nucleic acid of interest at said cleavage site by homologous recombination, the claim should be amended accordingly. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
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 38, 65-76 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 5-7, 10-12, 14-16 of U.S. Patent No. 11,268,065. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 38, 65-76 of the instant application are directed in part to a method for producing a genetically-modified human T cell that comprises an exogenous nucleic acid inserted in its chromosome, wherein said method comprises (i) transfecting a human T cell with a nucleic acid encoding the meganuclease of SEQ ID NO: 8, wherein the nucleic acid encoding the meganuclease of SEQ ID NO: 8 can be an mRNA, wherein said meganuclease binds and cleaves a recognition site that consists of the nucleotide sequence of SEQ ID NO: 3, wherein said recognition site is in a T cell receptor gene, thus producing a cleavage site, and (ii) transfecting said human T cell with an exogenous nucleic acid that encodes a chimeric antigen receptor via a recombinant AAV vector, wherein said AAV vector can be an AAV6 vector, wherein said exogenous nucleic acid is inserted in the chromosome by homologous recombination at the cleavage site. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 1, 5-7, 10-12, 14-16 of U.S. Patent No. 11,268,065 are directed to a method for producing a genetically-modified human T cell comprising a modified human TCR alpha constant region gene, said method comprising: (a) introducing into a human T cell an mRNA comprising a first nucleic acid encoding an engineered meganuclease, wherein said engineered meganuclease produces a cleavage site at a recognition site that consists of SEQ ID NO: 3 within said human TCR alpha constant region gene; and (b) introducing into said human T cell a second nucleic acid comprising an exogenous polynucleotide encoding a chimeric antigen receptor comprising an extracellular ligand-binding domain, a transmembrane domain, an intracellular co-stimulatory domain, and an intracellular signaling domain, wherein said second nucleic acid is introduced by contacting said human T cell with a recombinant adeno-associated virus (AAV) vector, including an AAV6 vector, comprising said second nucleic acid; wherein said second nucleic acid comprises, from 5′ to 3′: (i) a 5′ homology arm that is homologous to the 5′ upstream sequence flanking said cleavage site; (ii) said exogenous polynucleotide; and (iii) a 3′ homology arm that is homologous to the 3′ downstream sequence flanking said cleavage site; wherein the exogenous polynucleotide is inserted into said human TCR alpha constant region gene at said cleavage site by homologous recombination, and further wherein said genetically-modified human T cell does not express an endogenous TCR on the cell surface. The recognition site of SEQ ID NO: 3 of U.S. Patent No. 11,268,065 is identical to the recognition site of SEQ ID NO: 3 of the instant application. The specification of U.S. Patent No. 11,268,065 discloses the meganuclease of SEQ ID NO: 8 as a preferred embodiment of the genus of meganucleases required by the claimed method. The meganuclease of SEQ ID NO: 8 of U.S. Patent No. 11,268,065 is identical to the meganuclease of SEQ ID NO: 8 of the instant application. Therefore, the method of claims 38, 65-76 of the instant application is deemed an obvious variation of the method of claims 1, 5-7, 10-12, 14-16 of U.S. Patent No. 11,268,065 in view of the preferred embodiment disclosed.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
October 7, 2026
