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 reply to the Restriction Requirement, dated July 29, 2025, has been received. By way of this submission, applicant has elected an autoimmune disease, a mutant calcineurin B with a sequence of SEQ ID NO: 15, tacrolimus, and a chimeric antigen receptor (CAR) that binds CD19.
It is noted that the elected SEQ ID NO: 15 is not a mutant calcineurin B sequence; it is assumed that the elected species should be SEQ ID NO: 32, which is recited in claim 15. Applicant is requested to confirm this was made in error.
Applicant’s election in the reply filed above 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 § 818.01(a)).
Claims 4-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 29, 2025.
Claims 1-3, 7-10, and 14-20 are currently under examination before the Office.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at page 16. 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.
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.
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.
Claims 1-2, 7-8, 10, 14-16 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Cost (WO2019210280A1, cited in IDS) in view of Yoon (J Biomed Biotechnol. 2010:2010:686480).
Cost teaches a method of treating an autoimmune disease by administering cells bearing a chimeric antigen receptor (CAR) and a mutant version of calcineurin B which is resistant to a calcineurin inhibitor (para. 0037-0040 and 0133).
Cost further teaches that the mutant version of calcineurin B is CNb30 (para. 0040 and 0073). Applicant's specification at pages 25-26 states that CnB30 comprises the mutations L124T and K125-LA-Ins relative to SEQ ID NO: 31, and CnB30 has the amino acid shown as SEQ ID NO: 32. Cost therefore inherently teaches this limitation of claims 14-15 and 19-20.
Cost further teaches that the mutant version of calcineurin B confers resistance to tacrolimus (FK506) and cyclosporin A (CsA) (para. 0039), which is pertinent to claims 10 and 18.
Cost further teaches that the cells are allogeneic to the subject (para. 0136), which is pertinent to claims 8 and 16.
However, Cost does not teach a subject who is receiving or has received treatment with a calcineurin inhibitor.
Yoon teaches that tacrolimus is useful in the treatment of the autoimmune disease systemic lupus erythematosus (SLE) (e.g., page 3, right column).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Cost and Yoon to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Cost and Yoon are concerned with the treatment of autoimmune diseases. CAR-T cells and tacrolimus were known to be useful in treating autoimmune disease, according to Cost and Yoon respectively. The CAR-T cells of Cost would be particularly useful in combination with the treatment of Yoon, since they would be resistant to elimination by tacrolimus. The use of the cells of Cost, which are resistant to tacrolimus, would naturally solve this problem in the art. One of ordinary skill could combine the treatments of Cost and Yoon by known methods, with each component of the combination performing their known, usual function, and the combination would have yielded nothing more than predictable results.
Claims 3, 9, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Cost and Yoon as applied to claims 1 and 7 above, and further in view of Radic (US20200085871A1).
The teachings of Cost and Yoon have been discussed supra. However, Cost and Yoon do not teach a CAR that binds an autoantigen associated with the autoimmune disease.
Radic teaches a method of treating an autoimmune disease by administering cytotoxic T cells that express a chimeric antigen receptor (CAR) (para. 0014).
Radic further teaches that the CAR may target CD19 (para. 0015).
Radic further teaches that anti-CD19 CAR-T cell therapy is useful in eradicating CD19 B cells from autoimmune subjects or patients that are responsible for autoimmune diseases (para. 0461).
Radic further teaches a plurality of doses (para. 0498), which is pertinent to claims 9 and 17.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Cost, Yoon, and Radic to arrive at the claimed invention. Treatments of autoimmune diseases with CAR-T cells were known in the art according to both Cost and Radic. Whereas Cost teaches a CAR-T cell with a mutant version of calcineurin B which is resistant to a calcineurin inhibitor, Radic teaches CD19 as a target for treating autoimmune diseases, as CD19 B cells are of importance in autoimmune disease. One of ordinary skill could apply the anti-CD19 CAR of Radic to the method of Cost and Yoon by known methods, with each component of the combination performing their known, usual function, and the combination would have yielded nothing more than predictable results.
All the claimed elements were known in the prior art and one of ordinary skill in the art could have arrived at the claimed invention by using known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-3, 7-10, and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30 and 31 of copending Application No. 17/915,802 in view of Cost, Yoon, and Radic.
The '802 application claims a method for treating a disease, comprising administering a pharmaceutical composition to a subject, which comprises a plurality of effector immune cells which express a cell surface receptor or receptor complex which specifically binds an antigen recognition receptor of a target immune cell, and which are engineered to be resistant to one or more calcineurin inhibitors; and administering the calcineurin inhibitor to the subject (claim 31).
However, the '802 application does not claim a CAR.
Cost teaches a method of treating an autoimmune disease by administering cells bearing a chimeric antigen receptor (CAR) and a mutant version of calcineurin B which is resistant to a calcineurin inhibitor (para. 0037-0040 and 0133).
Cost further teaches that the mutant version of calcineurin B is CNb30 (para. 0040 and 0073). Applicant's specification at pages 25-26 states that CnB30 comprises the mutations L124T and K125-LA-Ins relative to SEQ ID NO: 31, and CnB30 has the amino acid shown as SEQ ID NO: 32. Brewin therefore inherently teaches this limitation of claims 14-15 and 19-20.
Cost further teaches that the mutant version of calcineurin B confers resistance to tacrolimus (FK506) and cyclosporin A (CsA) (para. 0039), which is pertinent to claims 10 and 18.
Cost further teaches that the cells are allogeneic to the subject (para. 0136), which is pertinent to claims 8 and 16.
Yoon teaches that tacrolimus is useful in the treatment of the autoimmune disease systemic lupus erythematosus (SLE) (e.g., page 3, right column).
Radic teaches a method of treating an autoimmune disease by administering cytotoxic T cells that express a chimeric antigen receptor (CAR) (para. 0014).
Radic further teaches that the CAR may target CD19 (para. 0015).
Radic further teaches that anti-CD19 CAR-T cell therapy is useful in eradicating CD19 B cells from autoimmune subjects or patients that are responsible for autoimmune diseases (para. 0461).
Radic further teaches a plurality of doses (para. 0498), which is pertinent to claims 9 and 17.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '802 application the teachings of Cost, Yoon, and Radic to arrive at the claimed invention. Starting from the method claimed by the '802 application, one or ordinary skill could follow the teachings of Cost, Yoon, and Radic in order to arrive at the claimed subject matter of the instant invention, as Cost teaches the claimed mutant version of calcineurin B, Yoon teaches tacrolimus for the treatment of autoimmune disease, and Radic teaches anti-CD19 CAR-T cell therapy for treatment of autoimmune disease. Each component of the combination would perform their known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Brewin (Blood. 2009 Nov 26;114(23):4792-803, cited in IDS) teaches that the function of infused T cells is impaired by immunosuppressive therapy such as tacrolimus. Brewin further teaches a cytotoxic T lymphocyte that is resistant to the calcineurin inhibitor tacrolimus (page 4792, right column, second paragraph). Brewin further teaches that such cells are useful in patients that are immunosuppressed (abstract and page 4801, left column, last paragraph).
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644