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
Claims 45-48, 54, 56, 59, and 65-67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/23/2024.
Claim Status
Claims 4-9, 11, 13-15, 18-19, 25-30, 32, 34-36, 39-40, 43-44, 49-53, 57-58, 60-64, and 68-72 are cancelled. Claims 1-3, 10, 12, 16-17, 20-24, 31, 33, 37-38, 41-42, 45-48, 54, 56, 59, and 65-67 as filed on 23 September 2025 are pending. Claims 45-48, 54, 56, 59, and 65-67 are withdrawn. Claims 1-3, 10, 12, 16-17, 20-24, 31, 33, 37-38, and 41-42 are under examination.
Rejections Withdrawn
Rejection of claims 1-3, 10, 12, 17, 20-24, 31, 33, 38, 41-42 under 35 U.S.C. 112(a) is withdrawn with applicant amendment of claims to require the CDRs of the antigen binding domains of the claims.
Rejection of claim 24 under 35 U.S.C. 112(b) is withdrawn with applicant amendment of claims.
New Rejection Necessitated By Applicant Amendment of Claims
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 1-3, 10, 17, 20-24, 38, and 41-42 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.
Claim 1 subpart (a) states the antigen binding domain is encoded by a nucleotide sequence of the listed SEQ ID NO. SEQ ID NO: 31 is an amino acid sequence. Claim 1 subpart (b) states it is to an amino acid sequence selected from the listed and the listed includes SEQ ID NO: 32. SEQ ID NO: 32 is a nucleic acid sequence.
Subpart a and b of claim 1 are both thus indefinite.
This same error is repeated in claim 22.
All dependent claims 2-3, 10, 17, 20-21, 23-24, 38, and 41-42 inherit this indefiniteness without correcting the sequences and are also rejected under 112b.
For examination purposes examiner searched the claims as SEQ ID NO: 31 in subpart (b) and SEQ ID NO: 32 as part of subpart (a).
Rejections Maintained – Amendment of Rejection Necessitated By Applicant Amendment of Claims
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 10, 20-24, 31, and 41-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jin (CN 110564749 A) (OF RECORD).
Regarding claims 1-3 and 21, Jin teaches a vector comprising the nucleotide encoding EGFR806-41BB CAR (Figure 1), wherein the EGFR806-41BB CAR is comprised of the anti-EGFR antibody 806 which binds EGFRvIII and wild type EGFR (figure 1; page 2 in last paragraph and page 3 in lines 1-2). Jin teaches the 806 antibody in a EGFR806-41BB CAR T is comprised of the scFv of antibody 806, a CD8 transmembrane domain and an intracellular domain of 4-1BB (page 11 in par 3). Antibody 806 is the elected antibody of SEQ ID NO: 79 and 80 which comprises the VL of SEQ ID NO: 3 and SEQ ID NO: 4 and the CDRs of claims 8-9.
Regarding claim 10, Jin teaches the CAR comprises a hinge (abstract) and further teaches it is a CD8 alpha hinge (page 4 in (2)(1)). The hinge sequence in subpart b of the claims is not required.
Regarding claim 20, Jin teaches a CAR of the instant claims which would inherently have the binding activity of claim 20.
Regarding claims 22-24, 31 and 41, Jin teaches a host cell that expresses the vector comprising the nucleic acid encoding the CAR (page 8 in pars 2-4). Jin teaches the anti-EGFR antibody 806 which binds EGFRvIII and wild type EGFR (page 2 in last paragraph and page 3 in lines 1-2). Jin teaches the 806 antibody in a CAR T with the scFv of antibody 806, a CD8 transmembrane domain and an intracellular domain of 4-1BB (page 11 in par 3). Antibody 806 is the elected antibody of SEQ ID NO: 79 and 80 which comprises the VL of SEQ ID NO: 3 and SEQ ID NO: 4 and the CDRs of claims 29-30. The CAR taught by Jin would inherently have the binding activity of claim 41.
Regarding claims 42, Jin teaches the use of T cells from human patients (page 9 in last 2 paragraphs).
Applicant Arguments
Applicant argues that the amendment to the claims require elements of the CAR sequence not taught in Jin. These elements were amended into the claims from previously not rejected under 25 U.S.C. 102 claims 3 and 24.
Response to Arguments
Applicant's arguments filed 23 September 2025 have been fully considered but they are not persuasive.
The amendment of claims 1 and 22 do not require elements not taught by Jin. The subparts of claims 1 and 22 are all in the alternative so only 1 of subparts (a)-(f) falls within the metes and bounds of the claim. The claims require a CAR comprising an antigen binding domain capable of binding multiple isoforms of EGFR, a transmembrane domain, and an intracellular domain and further requires one of the subparts (a)-(f) as subpart (e) states or before the final subpart. Subparts c to f require only the VH and VL sequences or the CDRs of the sequences of the VH and VL in a CAR. Jin as previously stated and shown above with minor revisions required by applicant amendment of claims teaches the VH and VL of the claims in a CAR that further comprises a transmembrane domain, and an intracellular domain.
Rejections Maintained – Amendment of Rejection Necessitated By Applicant Amendment of Claims
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, 10, 12, 16, 22, 24, 33, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Jin (CN 110564749 A) (OF RECORD) and Golosov (WO 2017181119 A2) (OF RECORD).
Regarding claim 1, Jin teaches a vector comprising the nucleotide encoding EGFR806-41BB CAR (Figure 1) and further teaches the anti-EGFR antibody 806 which binds EGFRvIII and wild type EGFR (page 2 in last paragraph and page 3 in lines 1-2). Jin teaches the 806 antibody in a CAR T with the scFv of antibody 806, a CD8 transmembrane domain and an intracellular domain of 4-1BB (page 11 in par 3). Antibody 806 is the elected antibody of SEQ ID NO: 79 and 80 which comprises the VL of SEQ ID NO: 3 and SEQ ID NO: 4 and the CDRs of claims 8-9.
Regarding claim 10, Jin teaches the CAR comprises a hinge (abstract) and further teaches it is a CD 8 alpha hinge (page 4 in (2)(1)).
Regarding claims 16 and 33, Jin teaches a host cell that expresses the vector comprising the nucleic acid encoding the CAR (page 8 in pars 2-4). Jin teaches the anti-EGFR antibody 806 which binds EGFRvIII and wild type EGFR (page 2 in last paragraph and page 3 in lines 1-2). Jin teaches the 806 antibody in a CAR T with the scFv of antibody 806, a CD8 transmembrane domain and an intracellular domain of 4-1BB (page 11 in par 3). Antibody 806 is the elected antibody of SEQ ID NO: 79 and 80 which comprises the VL of SEQ ID NO: 3 and SEQ ID NO: 4 and the CDRs of claims 29-30. Instant SEQ ID NO: 13 is to 4-1BB which is taught in the CAR of Jin (page 11 in par 3). Instant SEQ ID NO: 14 is CD 3 zeta intracellular domain which is taught by Jin (page 4 in (2)(1)).
Jin does not teach the sequences of instant SEQ ID NO: 11-14, which encode the amino acids of SEQ ID NO: 72, 74, 76, and 78, which comprise the CAR of claims 16 and 37 and encodes the amino acids of claims 19 and 40.
This deficiencies are filled by Golosov.
Golosov teaches the production of CAR T cells (abstract). Instant SEQ ID NO: 11 of a CD8 alpha hinge matches Golosov’s SEQ ID NO: 804, instant SEQ ID NO: 12 of a CD8 transmembrane domain matches Golosov’s SEQ ID NO: 34, instant SEQ ID NO: 13 of a 4-1BB intracellular domain which matches Golosov’s SEQ ID NO: 118, and instant SEQ ID NO: 14 a CD3 CD 3 zeta intracellular domain which also matches Golosov’s SEQ ID NO: 118.
Golosov teaches the CD8 alpha hinge, the CD8 transmembrane domain, and the intracellular domains of 4-1BB and CD3 zeta in a CAR (Table 2 and page 60 in lines 6-14).
Golosov teaches the CAR comprises an antigen binding domain that targets EGFRvIII (page 63 in lines 20-25, page 72 in lines 8-13 and table 6). Golosov further teaches a vector comprising a nucleic acid encoding the CAR (claims 68-77 and page 10 in lines 19-25). It would have been obvious at the time the application was filed to substitute the CD8 alpha hinge and transmembrane domains and intracellular domains of 4-1BB and CD3 zeta taught encoded by a nucleotide in a vector by Jin with the sequences of CD8 alpha hinge and transmembrane domains and intracellular domains of 4-1BB and CD3 zeta taught by Golosov. Jin and Golosov are both teaching a CAR comprising an anti-EGFRvIII antigen binding domain, CD8 alpha hinge and transmembrane domain and intracellular domains of 4-1BB and CD3 zeta, and both teach the CAR encoded by nucleic acids. The CAR domains would have been art equivalent making their substitution obvious. There would have been a reasonable expectation of success as the CARs of Jin and Golosov are using equivalent domains with an EGFRvIII binding CAR.
Applicant Arguments
Applicant argues the rejection under 35 U.S.C. over Jin has been overcome and this overcomes the rejection under 35 U.S.C. 103 as being unpatentable over Jin (CN 110564749 A) (OR RECORD) and Golosov (WO 2017181119 A2) (OR RECORD). Applicant argues Gosolov does not cure the deficiencies of Jin.
Response to Arguments
Applicant's arguments filed 23 September 2025 have been fully considered but they are not persuasive.
As argued under the 35 U.S.C. 102 rejection the claims are not limited to material not taught in Jin and thus the arguments are not persuasive as there are no deficiencies to cure.
Rejections Maintained – Amendment of Rejection Necessitated By Applicant Amendment of Claims
Claims 1, 17, 22, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Jin (CN 110564749 A) (OR RECORD), Golosov (WO 201717119 A2) (OR RECORD), Wang et. al. Cancer Immunol Res. 3(7):815-826. (2016) (OF RECORD), and Müller et. al. J Immunother. 38(5):197-210 (2015) (OF RECORD).
Regarding claim 1, Jin teaches a vector comprising the nucleotide encoding EGFR806-41BB CAR (Figure 1) and further teaches the anti-EGFR antibody 806 which binds EGFRvIII and wild type EGFR (page 2 in last paragraph and page 3 in lines 1-2). Jin teaches the 806 antibody in a CAR T with the scFv of antibody 806, a CD8 transmembrane domain and an intracellular domain of 4-1BB (page 11 in par 3). Antibody 806 is the elected antibody of SEQ ID NO: 79 and 80 which comprises the VL of SEQ ID NO: 3 and SEQ ID NO: 4 and the CDRs of claims 8-9.
Regarding claim 22, Jin teaches a host cell that expresses the vector comprising the nucleic acid encoding the CAR (page 8 in pars 2-4). Jin teaches the anti-EGFR antibody 806 which binds EGFRvIII and wild type EGFR (page 2 in last paragraph and page 3 in lines 1-2).
Jin does not teach a CAR in a killer cell immunoglobulin-like receptor (KIR) or the nucleic acid encoding the CAR further encoding DAP12.
These deficiencies are filled by Golosov, Wang, and Müller.
Golosov teaches the CAR comprises an antigen binding domain that targets EGFRvIII (page 63 in lines 20-25, page 72 in lines 8-13 and table 6).
Golosov teaches the CAR comprises one or more components of a KIR (page 195 in lines 12-24). Golosov further teaches the CAR comprises a stimulator molecule expressed by an immune effector cell including cytoplasmic signaling sequence of DAP12 (pag 38 in lines 35-36 and page 39 in lines 1-11 in particular in line 10 and page 195 in lines 12-24). This teaches the use of an anti-EGFRvIII CAR with KIR and DAP12 components.
Wang teaches T cells modified to express KIR-CAR and DAP12 exhibit superior antitumor activity when compared to first and second generation CARs (abstract)
Müller teaches an anti-EGFRvIII CAR comprising DAP12 resulted in a moderate but significant delay in tumor growth and increased median survival time (Abstract). This was in a mouse model showing in vivo results (page 11 in last paragraph and onto page 12).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to combine the anti-EGFRvIII CAR of Jin with the KIR-CAR and DAP12 components taught by Golosov, Wang, and Müller. One of skill in the art would have been motivated to explore further elements of a CAR that improves its effectiveness. Golosov, Wang, and Müller teach increased effectiveness of CARs in treatment of cancer. Golosov and Müller teach the KIR and DAP12 components with an anti-EGFRvIII CAR. There would have been a reasonable expectation of success as Golosov and Müller teach the use of these components with CARs targeting the same antigen as Jin.
Applicant Arguments
Applicant argues the rejection under 35 U.S.C. over Jin has been overcome and this overcomes the rejection under 35 U.S.C. 103 as being unpatentable over Jin (CN 110564749 A) (OR RECORD), Golosov (WO 2017181119 A2) (OR RECORD), Wang et. al. Cancer Immunol Res. 3(7):815-826. (2016) (OR RECORD), and Müller et. al. J Immunother. 38(5):197-210 (2015) (OR RECORD).
Applicant argues Gosolov, Wang, and Müller do not cure the deficiencies of Jin.
Response to Arguments
Applicant's arguments filed 23 September 2025 have been fully considered but they are not persuasive.
As argued under the 35 U.S.C. 102 rejection the claims are not limited to material not taught in Jin and thus the arguments are not persuasive as there are no deficiencies to cure.
Rejections Maintained – Amendment of Rejection Necessitated By Applicant Amendment of Claims
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.
A single applicant argument was provided for the Double Patenting Rejections so a single response to arguments has been done at the end of all double patenting rejections.
Claims 1, 3, 10, 17, 21-22, 31, 38, and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 7, 10, 12, 17, 25, 29, 31, 34, 37-38, 41-42, 45, 52, 54, 56, 61, 63-64, 68, 70-71, 76, 78, 84, and 86-87 of copending Application No. 17432868 (reference application), as evidenced by Irmer et. al. Oncogene. 26:5693-5701. (2007). (OR RECORD). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1, 3 and 22-24, the reference application recites an anti-EGFRvIII CAR comprising a transmembrane domain, an intracellular signaling domain, and a stimulatory domain (claim 45). A CAR that binds EGFRvIII domain of EGFR would bind the isoforms of EGFR that have mutations of the tyrosine kinase domain as evidenced by Irmer . Irmer shows that the EGFR kinase domain has multiple mutations (abstract and Figure 1). The reference application recites a cell comprising a nucleic acid encoding the CAR (63-64).
Regarding claims 10 and 31, the reference application recites the CAR comprises a hinge region (claim 54).
Regarding claims 17 and 38, the refence application recites the signaling domain of KIRDS2 (claim 56).
Regarding claims 42-44, the reference application recites a vector in a cell that is an autologous T cell (claim 68) and further teaches the subject being treated with autologous cells is a human (claim 76).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 10, 12, 16-17, 20-24, 31, 33, 37-38, and 41-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 7, 10, 12, 17, 25, 29, 31, 34, 37-38, 41-42, 45, 52, 54, 56, 61, 63-64, 68, 70-71, 76, 78, 84, and 86-87 of copending Application No. 17432868 (reference application) in view of Jin (CN 110564749 A) (OR RECORD), Golosov (WO 201717119 A2) (OR RECORD), Wang et. al. Cancer Immunol Res. 3(7):815-826. (2016) (OR RECORD), and Müller et. al. J Immunother. 38(5):197-210 (2015) (OR RECORD).
The recitations of the reference application from the previous rejection are incorporated here in full.
The reference application further recites the transmembrane domain is CD8 (claim 52) and the intracellular domains of 4-1BB and CD3 zeta (claim 56).
The reference application does not recite the antigen binding domains of the reference claims or the sequences of the hinge and intracellular domains of the instant claims. The reference application does not recite use of a DAP12 domain.
These deficiencies are filled by Jin, Golosov, Wang, and Müller.
The teachings of Jin, Golosov, Wang, and Müller from the art rejections are incorporated here in full.
Jin teaches a CAR comprising an anti-EGFRvIII domain of the instant claims in a CAR that further comprises the intracellular domain and a CD8 alpha hinge as previously described.
Golosov teaches the sequences of the a CD8 alpha hinge, the CD8 transmembrane domain, and 4-1BB and CD3 zeta intracellular domains of the instant claims with an anti-EGFRvIII CAR as previously described. Golosov and Müller with Wang teach the utility and advantages of KIR and DAP12 components in an anti-EGFRvIII CAR.
It would have been obvious at the time the application was filed to substitute the anti-EGFRvIII scFv of the reference application with the anti-EGFRvIII of 806 taught by Jin and required by the claims. One of skill in the art would be motivated to produce varying CARs that bind EGFR for use in treatment of cancer. There would have been a reasonable expectation of success as the reference application and Jin teach CARs that can vary the scFv. This would produce a CAR that binds the specific EGFR isoforms of the claims and bind EGFR as a heterodimer, homodimer, or oligomer.
It would have been obvious at the time the application was filed to substitute the CD8 alpha hinge and transmembrane domains and intracellular domains of 4-1BB and CD3 zeta encoded by a nucleic acid recited by the reference application with the sequences of CD8 alpha hinge and transmembrane domains and intracellular domains of 4-1BB and CD3 zeta taught by Golosov. The reference application, Jin, and Golosov are both teaching a CAR comprising an anti-EGFRvIII antigen binding domain, CD8 alpha hinge and transmembrane domain and intracellular domains of 4-1BB and CD3 zeta. The CAR domains would have been art equivalent making their substitution obvious. There would have been a reasonable expectation of success as the CARs of the reference application and Golosov are using equivalent domains with an EGFRvIII binding CAR.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to combine the anti-EGFRvIII CAR encoded by a nucleic acid of the refence application and Jin with the KIR-CAR and DAP12 components taught by Golosov, Wang, and Müller. One of skill in the art would have been motivated to explore further elements of a CAR that improves its effectiveness. Golosov, Wang, and Müller teach increased effectiveness of CARs in treatment of cancer. Golosov and Müller teach the KIR and DAP12 components with an anti-EGFRvIII CAR. There would have been a reasonable expectation of success as Golosov and Müller teach the use of these components with CARs targeting the same antigen as Jin and the reference application.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 10, 17, 21-22, 24, 31, 38, and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35, 37-57, 59-62, 64-75, 77-79, and 81 of copending Application No. 18604288 (reference application), as evidenced by Irmer et. al. Oncogene. 26:5693-5701. (2007). (OR RECORD). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1 and 3, the reference application recites a polynucleotide that encodes a CAR that binds EGFR that comprises an scFv, a transmembrane domain, and an intracellular domain (claims 1-2).
Regarding claim 10, the reference application recites a CAR of SEQ ID NO: 35 or 75 which comprise a hinge (claim 54).
Regarding claims 17-18, the reference application recites an intracellular domain of a KIR and a costimulatory domain of DAP12 (claim 17).
Regarding claim 21-22, and 24, the reference application recites an expression vector the nucleic acid (claims 41-42) and further recites a modified immune cell comprising the vector (claim 49). The reference application recites a polynucleotide that encodes a CAR that binds EGFR that comprises an scFv, a transmembrane domain, and an intracellular domain (claims 1-2).
Regarding claim 31, the reference application recites a CAR of SEQ ID NO: 35 or 75 which comprise a hinge (claim 54).
Regarding claims 38-39, the reference application recites an intracellular domain of a KIR and a costimulatory domain of DAP12 (claim 17).
Regarding claims 42-44, the reference application recites a modified autologous human T cell (*claims 60-62 and 64-65).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 10, 12, 16-17, 20-24, 31, 33, 37-38, and 41-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35, 37-57, 59-62, 64-75, 77-79, and 81 of copending Application No. 18604288 (reference application) in view of Jin (CN 110564749 A) (OR RECORD), Golosov (WO 201717119 A2) (OR RECORD),
The recitations of the previous rejection are incorporated here in full.
The reference application recites a transmembrane domain of alpha CD8 (claim 13).
The reference application recites a costimulatory domain of 4-1BB and CD3 zeta (claims 17 and 19-20).
The reference application does not recite the anti-EGFR scFv of the dependent claims of antibody 806. The reference application does not recite the sequences of the hinge, transmembrane domain, or intracellular/costimulatory domains of the instant claims.
These deficiencies are filled by Jin and Golosov.
The teachings of Jin and Golosov from the previous art and double patenting rejections are incorporated here in full.
It would have been obvious at the time the application was filed to substitute the anti-EGFR scFv encoded by a nucleic acid of the reference application with the anti-EGFRvIII of 806 taught by Jin and required by the claims. One of skill in the art would be motivated to produce varying CARs that bind EGFR for use in treatment of cancer. There would have been a reasonable expectation of success as the reference application and Jin teach CARs that can vary the scFv. This would produce a CAR that binds the specific EGFR isoforms of the claims and bind EGFR as a heterodimer, homodimer, or oligomer.
It would have been obvious at the time the application was filed to substitute the hinge, CD8 alpha transmembrane domain and intracellular domains of 4-1BB and CD3 zeta recited by the reference application with the sequences of CD8 alpha hinge and transmembrane domains and intracellular domains of 4-1BB and CD3 zeta taught by Golosov. The reference application, Jin, and Golosov are both teaching a CAR comprising an anti-EGFR antigen binding domain, hinge, CD8 alpha transmembrane domain, and intracellular domains of 4-1BB and CD3 zeta. The CAR domains would have been art equivalent making their substitution obvious. There would have been a reasonable expectation of success as the CARs of the reference application and Golosov are using equivalent domains with an EGFR binding CAR.
This is a provisional nonstatutory double patenting rejection.
Applicant Arguments
Applicant did not provide an argument for the double patenting rejections.
Response to Arguments
Rejections are maintained.
Conclusion
No claims allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/F.E./ /Meera Natarajan/Primary Examiner, Art Unit 1643