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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 20 October 2025 has been entered. Applicant indicates on the Request for Continued Examination (RCE) Transmittal, 20 October 2025, that the response of 20 October 2025 be considered.
Claim status
In the reply on 20 October 2025, claims 16, 18-22, 24-26, 28-29, 31-32 and 36 are withdrawn and claims 3-6, 8-9, 11-13, 15, 17, 23, 27, 30, and 33-34 were previously canceled. Therefore, claims 1-2,7,10,14,16,18-22,24-26,28-29,31-32 and 35-36 are herein pending.
Election/Restrictions
Applicant elected without traverse of Group I, claims 1-2, 7, 10, 14, and 35, drawn to an engineered immune cell comprising a SIRPalpha polypeptide that binds to human CD47 for examination, in the reply filed on 11 September 2024.
Applicant previously elected (a) SEQ ID NO: 34 as a species of SIRPalpha polypeptide, (b) SEQ ID NO: 3 as a species of an extracellular antigen, and (c) SEQ ID NO: 41 as a species of a MUC 16 scFv. Claims 1-2, 7, 10, 14, and 35 of the elected Group I read on the above species.
SEQ ID NO: 41 is free of the prior. The species election requirement, as set forth in the Office action mailed on June 25, 2024, has been reconsidered pursuant to MPEP § 821.04(a). The Species election of the MUC16 scFV comprising SEQ ID NO: 41 and 44 is hereby withdrawn as to any claim that requires all the limitations of an allowable claim. SEQ ID NO: 44 has been rejoined as a species of MUC16 scFV.
Furthermore, applicant has canceled claims 16,18-22,24-26,28-29,31-32 and 36 of Groups 2 and 3.
Therefore, claims 1-2, 7, 10, 14, and 35 are herein under examination.
Priority
This application was filed 05/11/2021 and is a 371 application of PCT/US2019/060995 filed on 11/12/2019, which claims benefit to the Priority from Provisional Application 62760864, filed on 11/13/2018. Thus, the earliest possible priority for the instant application is 11/13/2018.
Withdrawn Objection to Abstract
The abstract objection is withdrawn due to applicant submits herewith a replacement abstract which is 55 words in length and is compliant with all provisions of MPEP §608.0l(b).
“Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a SIRPa polypeptide. Also disclosed herein are methods of enhancing the anti-tumor efficacy of an engineered immune cell comprising a tumor antigen-targeted chimeric antigen receptor by combining it with a SIRPa polypeptide.”
To move this prosecution Examiner needs to file this replacement abstract via the USPTO patent electronic filing system.
Withdrawn Rejections
The prior rejection of claims 1-2, 7, 10, 14, and 35 are newly 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 is withdrawn. The withdrawal is in light of applicant pointed out the paragraph [0126] of the published specification is adequate support for the negative limitation "is not fused to an immunoglobulin Fe domain" in claim 1 due to the positive, alternative recitation of SIRPa fused to immunoglobulin Fe domain in paragraph [0126] as explained in MPEP 2173.05(i).
New Claim Objections
Claim 1 is objected to because of the following informalities: abbreviations such as “SIRP[Symbol font/0x61]” should be spelled out in full at the first encounter in the claims. Appropriate correction is required.
Modified 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 2, 14 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Gottschalk et al. (WO2017184553A1; published on 26 October 2017; cited in IDS filed on 05/11/2021; hereinafter “Gottschalk”), in view of Ring et al. (US9944911B2; published on Apr. 17, 2018; cited in PTO892; hereinafter “Ring”). This rejection is maintained with modification for reasons of record and further explained below.
With respect to claim 1, Gottschalk discloses an engineered immune cell ([0040], claims 34-35 of Gottschalk)
a truncated (a derivative thereof (e.g., CV1)) SIRP[Symbol font/0x61] polynucleotide is transfected into cells ex vivo and the cells harboring the polynucleotide are locally delivered to tumors and/or tumor microenvironment, wherein the truncated SIRP[Symbol font/0x61] polypeptide (claims 1, 4, 7, 35 and 38; [0005] of Gottschalk);
-binds to human CD47 (claims 1, 4, 7, 35 and 38 of Gottschalk),
- viral vectors encoding SIRP[Symbol font/0x61] and SIRP[Symbol font/0x61]-Fc fusion proteins [0016], Fig. 2A (top), 5A-B of Gottschalk). Therefore, Gottschalk discloses an engineered immune cell with the vector encoding SIRP[Symbol font/0x61] without fused to an immunoglobulin Fe domain,
-is secreted ([0033], [0096] of Gottschalk),
b) a receptor that binds to a target antigen and/or nucleic acid encoding the receptor (claim 20, 24-25, 30). Furthermore, Gottschalk teaches use of the immune cells for cancer therapy ((0013] of Gottschalk).
Regarding claim 1, Gottschalk is silent to the truncated SIRP[Symbol font/0x61] polypeptide having the amino acid sequence of SEO ID NOs: 34 or 35. However, such was known in the prior art.
Ring discloses a high affinity SIRP[Symbol font/0x61] polypeptides and analogs thereof are provided, which may be referred to generically as high affinity SIRP[Symbol font/0x61] reagents. The reagents are variants of the native human SIRP[Symbol font/0x61] protein (Col. 13 lns 21-23 of Ring). Furthermore, Ring discloses that the high affinity SIRP[Symbol font/0x61] reagent of the invention comprises at least one amino acid modification within the d1 domain of SIRP[Symbol font/0x61], which domain is set forth in SEQ ID NOs: 1 or 10, which is 100% identical to instant application SEQ ID NOs: 34 and 35 respectively (see ABSS result dated 04/09/2025), and corresponds to residues 31 to 149 of the native human full-length human protein. The high affinity SIRP[Symbol font/0x61] reagent may comprise amino acid sequences other than SIRP[Symbol font/0x61] (Col. 13 lns 48-57, claim 1 of Ring); which include without limitation immunoglobulin Fc region sequences (Col. 13 lns 55-56 of Ring), wherein the polypeptide lacks the SIRP[Symbol font/0x61] transmembrane domain (Col. 13 lns 25-27 of Ring).
MPEP 2143 (B) states that simple substitution of one known element for another to obtain predictable results. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Accordingly, it would have been obvious to practice the engineered immune cell of Gottschalk and substitute the truncated SIRP[Symbol font/0x61] polypeptide having the amino acid sequence of SEO ID NO: 34 as taught by Ring with a reasonable expectation of success. One of ordinary skill would have been motivated to do so as taught by Ring because high-affinity SIRP[Symbol font/0x61] variants could be valuable therapeutics for a variety of human cancers (Col. 31 lns 9-11 of Ring). The skilled artisan would have had a reasonable expectation of success in combining the teachings of Gottschalk et al. and Ring et al. because each of these teachings both successfully generated engineered immune cell.
In regard to the reasonable expectation of success to choose the truncated SIRP[Symbol font/0x61] polypeptide sequence of SEO ID NO: 34 as taught by Ring, this was a well-known choose at the time of filing and required no more than routine recombinant DNA technology. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015); See MPEP 2106.05(d).
With respect to claims 2, Gottschalk discloses receptor is a chimeric antigen receptor ([0012], claim 30 of Gottschalk).
With respect to claims 14, Gottschalk discloses that the engineered immune cell is a natural killer cell and/or neutrophil ([0027] of Gottschalk).
With respect to claims 35, Gottschalk discloses that the method for treating of inhibiting tumor growth or metastasis in a subject comprising contacting a tumor cell with an effective amount of the engineered immune cell ([0048], [0049], wherein the bispecific antibody construct ([0012, [0050], [0067], claim 29 of Gottschalk) effectively prevent to activate immune cells that express FC receptors, including the TAMs, and upon activation the immune system is then stimulated to eradicate cancer cells ([0026], [0131], [0138]-[0140] and claim 25 of Gottschalk).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 2, 7 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over over Gottschalk et al. (WO2017184553A1; published on 26 October 2017; cited in IDS filed on 05/11/2021; hereinafter “Gottschalk”) and Ring et al. (US9944911B2; cited in PTO892; hereinafter “Ring”) as applied to claims 1, 2, 14 and 35 above, and further in view of Oda et al. (WO2016141347; cited in PTO892; hereinafter “Oda”).
As stated supra, regarding claims 1, Gottschalk discloses an engineered immune cell ([0040] ¶ of Gottschalk), a truncated (a derivative thereof (e.g., CV1)) SIRP[Symbol font/0x61] polynucleotide is transfected into cells ex vivo and the cells harboring the polynucleotide are locally delivered to tumors and/or tumor microenvironment, wherein the truncated SIRP[Symbol font/0x61] polypeptide -binds to human CD47 (claims 1, 4, 7, 35 and 38 of Gottschalk), and b) a receptor that binds to a target antigen and/or nucleic acid encoding the receptor, optionally wherein the target antigen is a tumor antigen (i.e., WT-1) (claims 138, 139, 158-159 of Gottschalk).
Regarding claim 7, Gottschalk is silent on chimeric antigen receptor comprises CD8 transmembrane domain. However, such was known in the prior art.
With respect to claims 2, 7 and 14, Oda teaches, an engineered immune cell to develop an adoptive T-cell cancer immunotherapy using a) a genetically modified T cell (CD4+ T cell or a CD8+ T cell (claims 150-152; p. 61 lines 11-27; p. 67 lines 10-14) comprising CAR having a CD47 binding domain which is a human SIRPα protein (claims 7, 144, 150, 166, and 169-170). Furthermore, Oda teaches that the receptor is a T cell receptor, or a chimeric antigen receptor (p. 34 lines 13-16; claims 7, 8, 161, 162) comprises
an extracellular antigen binding domain binds to the target antigen and/or comprises a single chain variable fragment (scFv) (p. 22 lines 4-19, p. 36 Extracellular Component ¶ and Claim 162).
a transmembrane domain (p. 35 lines 20-p. 36 lines 5); and
an intracellular domain (i.e., CD28 costimulatory domain, a CD3zeta, 4-1BB) (claims 27-28; p. 35 lines 20-p. 36 lines 5)
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the engineered immune cell of Gottschalk and combine the CAR having a CD47 binding domain as taught by Oda with a reasonable expectation of success. One of ordinary skill would have been motivated to do so as taught by Oda because antigen-specific T cell increased immune cell activity (p. 10 lns 21-26 of Oda). The skilled artisan would have had a reasonable expectation of success in combining the teachings of Gottschalk et al. and Oda et al. because each of these teachings both successfully generated engineered immune cell.
In regard to the reasonable expectation of success to choose the chimeric antigen receptor as taught by Oda, this was a well-known choose at the time of filing and required no more than routine recombinant DNA technology and cell culture technology. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015); See MPEP 2106.05(d).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 20 October 2025 are acknowledged.
Applicant argues that the Office has failed to cite any art that relates to an engineered immune cell comprising a truncated SIRPa polypeptide having the amino acid sequence of SEQ ID NO: 34 or SEQ ID NO: 35, wherein the truncated SIRPa polypeptide is not fused to an immunoglobulin Fe domain. Gottschalk, which merely teaches viral vectors encoding SIRPa and SIRPa-Fc fusion proteins for the treatment of cancer, does not teach or suggest any engineered immune cells (see remark p. 9 2nd ¶).
Applicant’s arguments with respect to primary art Gottschalk et al. have been considered, however they are not persuasive. As discussed in 103 rejection, Gottschalk discloses an engineered immune cell ([0040], claims 34-35, of Gottschalk); a truncated (a derivative thereof (e.g., CV1)) SIRP[Symbol font/0x61] polynucleotide is transfected into cells ex vivo and the cells harboring the polynucleotide are locally delivered to tumors and/or tumor microenvironment, wherein the truncated SIRP[Symbol font/0x61] polypeptide (claims 1, 4, 7, 35 and 38; [0005] of Gottschalk); binds to human CD47 (claims 1, 4, 7, 35 and 38 of Gottschalk); wherein the viral vectors encoding SIRP[Symbol font/0x61] and/or SIRP[Symbol font/0x61]-Fc fusion proteins [0016], Fig. 2A (top), 5A-B of Gottschalk). Therefore, Gottschalk discloses an engineered immune cell with the vector encoding SIRP[Symbol font/0x61] without fused to an immunoglobulin Fe domain; is secreted ([0033], [0096] of Gottschalk). Therefore, Gottschalk, teaches engineered immune cells; wherein viral vectors encoding SIRPa, (e.g., SIRPa in not Fc fusion proteins) for the cancer therapy.
Applicant argues that the Ring fails to teach any engineered cell, let alone an immune cell, expressing a truncated SIRPa polypeptide that is not fused to an immunoglobulin Fc domain. Rather, Ring merely teaches mutant SIRPa polypeptide constructs and uses thereof in treating cancer. Ring at Example 2. Moreover, Ring actually teaches that "single domain high-affinity SIRPa monomers are not sufficient to induce maximal phagocytosis on their own" and only therapeutically exemplifies Fc-SIRPa constructs in a cancer treatment model (see remark p. 10 3rd ¶).
Applicant’s arguments with respect to Ring et al. have been considered, however they are not persuasive. In response to Applicant's arguments in regard to Ring’s teaching away from the claimed invention, MPEP 2145 X(D1) states that "the prior art' s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). In here Ring discloses a high affinity SIRP[Symbol font/0x61] polypeptides and analogs thereof are provided, which may be referred to generically as high affinity SIRP[Symbol font/0x61] reagents. The reagents are variants of the native human SIRP[Symbol font/0x61] protein (Col. 13 lns 21-23 of Ring). Furthermore, Ring discloses that the high affinity SIRP[Symbol font/0x61] reagent of the invention comprises at least one amino acid modification within the d1 domain of SIRP[Symbol font/0x61], which domain is set forth in SEQ ID NOs: 1 or 10, which is 100% identical to instant application SEQ ID NOs: 34 and 35 respectively (see ABSS result dated 04/09/2025), and corresponds to residues 31 to 149 of the native human full-length human protein. The high affinity SIRP[Symbol font/0x61] reagent may comprise amino acid sequences other than SIRP[Symbol font/0x61] (Col. 13 lns 48-57, claim 1 of Ring); which include without limitation immunoglobulin Fc region sequences (Col. 13 lns 55-56 of Ring), wherein the polypeptide lacks the SIRP[Symbol font/0x61] transmembrane domain (Col. 13 lns 25-27 of Ring). Therefore, it would have been obvious to practice the engineered immune cell of Gottschalk and substitute the truncated SIRP[Symbol font/0x61] polypeptide having the amino acid sequence of SEO ID NO: 34 as taught by Ring with a reasonable expectation of success because engineered immune cells will have high-affinity SIRP[Symbol font/0x61] variants could be valuable therapeutics for a variety of human cancers (Col. 31 lns 9-11 of Ring).
Applicant argues that the Oda, which is merely relied upon as teaching generic CAR components, does not teach any engineered immune cells comprising SIRPa constructs, let alone SIRPa polypeptide constructs lacking an Fe domain. Office Action, page 11. Oda thus fails to remedy the aforementioned deficiencies of Gottschalk and Ring (see remark p. 11 2nd ¶).
Applicant’s arguments with respect to Oda et al. have been considered, however they are not persuasive. Oda teaches, an engineered immune cell to develop an adoptive T-cell cancer immunotherapy using a) a genetically modified T cell (CD4+ T cell or a CD8+ T cell (claims 150-152; p. 61 lines 11-27; p. 67 lines 10-14) comprising CAR having a CD47 binding domain which is a human SIRPα protein (claims 7, 144, 150, 166, and 169-170). Furthermore, Oda teaches that the receptor is a T cell receptor, or a chimeric antigen receptor (p. 34 lines 13-16; claims 7, 8, 161, 162). Therefore, it would have been obvious to practice the engineered immune cell of Gottschalk and combine the CAR having a CD47 binding domain as taught by Oda with a reasonable expectation of success because engineered immune cells will have antigen-specific T cell that could increase immune cell activity (p. 10 lns 21-26 of Oda).
Therefore, office have provided the detailed explanation why a person of ordinary skill in the art would possess a reasonable expectation in the Office's asserted combination, where such a finding is in addition to and separate from the motivation analysis. Honeywell at 12; KSR at 418-19. Therefore, combined teachings of Gottschalk, Ring, and Oda render the instant claims obvious because they teach or suggest each and every element of the claims, and also provide the rationale or motivation for a skilled artisan to combine or modify the teachings therein to arrive at the claimed subject matter with any reasonable expectation of success.
Subject matter free of art
Current application’s dependent claim 10 is claimed an engineered immune cell comprising a receptor that binds to a target antigen, wherein antigen binding domain comprises: a CD19 scFv having sequence identity to SEQ ID NO: 3 or SEQ ID NO: 4 and a MUC 16 scFv having at least 80% sequence identity to SEQ ID NO: 41 or SEQ ID NO: 44. Prior art does not teach or fairly suggest to prepare a genetically engineered immune cell comprising a CD19 scFv having sequence identity to SEQ ID NO: 3 or SEQ ID NO: 4 and a MUC 16 scFv having at least 80% sequence identity to SEQ ID NO: 41 or SEQ ID NO: 44.
Therefore, claim 10 is objected to as being dependent upon rejected base claims but would be free from prior if rewritten in an independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Examiner Contact Information
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684