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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/21/2026 has been entered.
Claim Status
Claims 3-9, 11, 13-15, 17-20, 24-30, 32, 34-36, 38-41, 43-44, 49-55, and 57-72are cancelled. Claims 1-2, 10, 12, 16, 21-23, 31, 33, 37, 42, 45-48, 56, and 73-118 as filed on are pending. Claims 45-48, 56, 79-81, 85, 91, 94-98, 104, 110-118 are withdrawn. Claims 1-2, 10, 12, 16, 21-23, 31, 33, 37, 42, 73-78, 82-84, 86-90, 92-93, 99-103, and 105-109 are under examination.
Rejections Withdrawn
Rejection of claims 1-3, 10, 17, 20-24, 38, and 41-42 under 35 U.S.C. 112(b) is withdrawn with applicant explanation.
Rejection of claims 1-3, 10, 20-24, 31, and 41-42 under 35 U.S.C. 102(a)(1) over Jin (CN 110567749) (Of Record) is withdrawn with applicant amendment of claims and resulting new search of claim limitations.
Rejection of claims 1, 10, 12, 16, 22, 24, 33, and 37 under 35 U.S.C. 103 over Jin (CN 110567749) (Of Record) and Golosov (WO 201718119 A2) (Of Record) is withdrawn with applicant amendment of claims and new search of claim limitations.
Rejection of claims 1, 17, 22, and 38 under 35 U.S.C. 103 over Jin (CN 110567749) (Of Record) , Golosov (WO 201718119 A2) (Of 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 J Immunother. 38(5):197-210 (2015) (OF RECORD) is withdrawn with applicant cancelation of claims.
The rejection under Double Patenting over 17432868 is withdrawn with applicant amendment of claims.
Applicant arguments dated 04/21/2026 regarding the withdrawn prior art and double patenting rejection over 17432868 were reviewed and fully considered by examiner, but they are moot as the new grounds of rejection necessitated by applicant amendment of claims do not rely on matters challenged in applicant arguments from 04/21/2026 remarks. Response to arguments regarding double patenting over copending 18604288 follow the rejection below.
New Rejections
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 1-2, 10, 12, 21-23, 31, 33, 42, 76-78, 82-84, 86-90, 92-93, 101-103, and 105-109 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jarjour (WO 2020123936 A1) (PTO-892).
Jarjour teaches an EGFR binding scFv of SEQ ID NO: 3 which matches the VL and VH domains scFv of instant SEQ ID NO: 2 which is the scFv of applicant elected scFv of 79. The sequence does not match as it varies in the linker domain at one amino acid. Alignment shown below.
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546
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Regarding claims 1-2 and 22-23, by teaching the VH and VL of the scFv of instant SEQ ID NO: 2 and instant SEQ ID NO: 79 Jarjour teaches an scFv that comprises a VL domain of instant SEQ ID NO: 3 and a VH domain of instant SEQ ID NO: 4. This would inherently have the required binding activity of binding the required isoforms of EGFR required by the applicant. Jarjour teaches a CAR comprising an scFv, a hinge domain, a transmembrane domain, and an intracellular domain comprising a costimulatory domain and an intracellular domain (Figure 1). Jarjour teaches polynucleotides encoding the CAR of Jarjour (page 56 in lines 4-21). Regarding the human immune cell required by claims 22-23, Jarjour teaches the use of human autologous immune effector cells (page 94 in lines 3-8).
Regarding claims 10, 12, 31, and 33, Jarjour teaches the CARs comprise CD8α hinge and transmembrane domains (page 61 in lines 1-13) and teaches that the polypeptides for use are obtained or isolated from human polypeptides teaching human CD8α for the hinge and transmembrane domains of Jarjour as required by claims 10 and 12 (page 65 in lines 1-3).
Regarding claim 21, Jarjour teaches a vector encoding their polypeptides (page 23 in lines 8-10 and page 56 in lines 4-17).
Regarding claim 42, Jarjour teaches the use of human autologous immune effector cells, and the use of T cells (page 94 in lines 3-11).
Regarding claim 76, Jarjour teaches the scFv of SEQ ID NO: 2 as previously described this comprises the VH of instant SEQ ID NO: 4 and the VL of instant SEQ ID NO: 3 as shown by the alignment previously shared in this rejection.
Regarding claims 77-78, the scFv of Jarjour’s SEQ ID NO: 2 does not comprise or consist of the linker of instant SEQ ID NO: 46. Instant SEQ ID NO: 46 consists of “GGGGSGGGGSGGGGS” which Jarjour teaches as (GGGGS)n where n= 1, 2, 3, 4, or 5. Jarjour further teaches these as suitable linkers (page 35 in lines 28-30 and page 36 in lines 1-2). This teaches the linker of instant SEQ ID NO: 46.
Regarding claim 82, Jarjour teaches suitable costimulatory domains include 4-1BB (page 46 in lines 22 and 27 and Figure 2).
Regarding claims 82-84 and 105-106, Jarjour teaches the costimulatory domain of 4-1BB (page 18 in lines 18 and 23) and further teaches instant SEQ ID NO: 76 in SEQ ID NO: 4, 5, and 6. Jarjour teaches the nucleic acid sequence encoding instant SEQ ID NO: 78 of instant SEQ ID NO: 13.
Regarding claims 86, 90, and 107, Jarjour teaches an intracellular signaling domain of CD3 zeta (page 39 in lines 21 and 27 and Figure 2). Jarjour further teaches that the polypeptides for use are obtained or isolated from human polypeptides teaching human CD3 zeta as required by claim 90 (page 65 in lines 1-3).
Regarding claims 87-89 and 108-109, Jarjour teaches instant SEQ ID NO: 78 in SEQ ID NO: 4 and by teaching a vector encoding their polypeptides (page 23 in lines 8-10 and page 56 in lines 4-17) Jarjour teaches the nucleic acid sequence encoding instant SEQ ID NO: 78 of instant SEQ ID NO: 14.
Regarding claims 92-93, Jarjour teaches a signal peptide as part of their CAR polypeptides (page 4 in lines 5-6) and further teaches instant SEQ ID NO: 70 followed by Gly Ser in SEQ ID NO: 4, 5, and 6.
Regarding claims 101-103, the scFv of Jarjour’s SEQ ID NO: 2 teaches the VL of instant SEQ ID NO: 3 and the VH of instant SEQ ID NO: 4 as previously described in the rejection, it does not comprise or consist of the linker of instant SEQ ID NO: 46. Instant SEQ ID NO: 46 consists of “GGGGSGGGGSGGGGS” which Jarjour teaches as (GGGGS)n where n= 1, 2, 3, 4, or 5. Jarjour further teaches these as suitable linkers (page 35 in lines 28-30 and page 36 in lines 1-2). This teaches the linker of instant SEQ ID NO: 46.
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, 31, 33, 37, 73-75, and 99-100 are rejected under 35 U.S.C. 103 as being unpatentable over Jarjour (WO 2020123936 A1) (PTO-892) and Golosov (WO 2017181119 A2) (Of Record).
The teachings of Jarjour from the 102 rejection are incorporated here in full.
Instant SEQ ID NO: 65 comprises a CAR of a CD8α signal peptide of instant SEQ ID NO: 70 in amino acids 1 to 21, Gly-Ser, then the scFv of instant SEQ ID NO: 2, amino acids 24 to 262, then the CD8α hinge domain of instant SEQ ID NO: 72, then the CD8α transmembrane domain of instant SEQ ID NO: 74, then a 4-1BB sequence of instant SEQ ID NO: 76, then a CD3 zeta domain comprising instant SEQ ID NO: 76.
Jarjour SEQ ID NO: 2 and CAR of SEQ ID NO: 4 teaches the CD8α signal of instant SEQ ID NO: 70 followed by Gly-Ser and the scFv of instant SEQ ID NO: 2 by combination of the VH and VL of SEQ ID NO: 4 and by teaching (GGGGS)n where n= 1, 2, 3, 4, or 5. Jarjour further teaches these as suitable linkers (page 35 in lines 28-30 and page 36 in lines 1-2). This teaches the linker of instant SEQ ID NO: 46 and used in the scFv of instant SEQ ID NO: 65. Jarjour teaches the costimulatory domain of 4-1BB (page 18 in lines 18 and 23) and further teaches instant SEQ ID NO: 76 in SEQ ID NO: 4, 5, and 6, which teaches the nucleic acid sequence encoding instant SEQ ID NO: 78 of instant SEQ ID NO: 13. Regarding amino acids 371 to 483 of instant SEQ ID NO: 65, which comprises the CD3 zeta of amino acids instant SEQ ID NO: 78, matches Jarjour SEQ ID NO: 4 amino acids 189 to 301.
Jarjour then teaches the signaling peptide, scFv, the 4-1BB and CD3 zeta domains of instant SEQ ID NO: 70, 2, 76, and 78 which are required in claims 73, 74-75, and 100 and found in instant SEQ ID NO: 65 of claims 16 and 37.
Jarjour teaches the CARs comprise CD8α hinge and transmembrane domains (page 61 in lines 1-13) and teaches that the polypeptides for use are obtained or isolated from human polypeptides teaching human CD8α for the hinge and transmembrane domains of Jarjour as required by claims 10 and 12 (page 65 in lines 1-3).
Jarjour does not teach the sequences of instant SEQ ID NO: 72 and 74 for the CD8α hinge and CD8α transmembrane domain and thus does not teach the complete CAR of instant SEQ ID NO: 65.
This deficiency is filled by Golosov.
Golosov teaches the production of CAR T cells (abstract).
Golosov teaches instant SEQ ID NO: 72 as a hinge used in a CAR in SEQ ID NO: 15, 978, 3019, and 3012, and teaches instant SEQ ID NO: 74 as a transmembrane domain use in a CAR in SEQ ID NO: 978, 3019, 3072.
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).
It would have been obvious at the time the application was filed to substitute the hinge and transmembrane domain of the EGFR binding CAR of Jarjour with the CD8α hinge and transmembrane domain of Golosov to produce the CAR of instant SEQ ID NO: 65. Gosolov teaches the substitution of hinge and transmembrane domains in a CAR as art equivalents that will have the same biological activity (see MPEP 2183) making the substitution prima facie obvious. One of skill in the art would further be motivated by Jarjour’s teaching towards using human obtained peptides for use in their fusion proteins. There would have been a reasonable expectation of success as Jarjour teaches the hinge and transmembrane domain as interchangeable between types and Golosov teaches the successful use of CD8α hinge and transmembrane domains of the instant sequence in CARs including ones that bind EGFR.
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 1-2, 10, 12, 16, 21-23, 31, 33, 37, 42, 73-78, 82-84, 86-90, 92-93, 99-103, and 105-109 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-35, 37-57, 59-62, 64-75, 77-79, and 81 of copending Application No. 18604288 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference application recites a nucleotide sequence that encodes a CAR that binds EGFR or an isoform thereof where the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain (claim 1).
Unelected scFv of instant SEQ ID NO: 32 matches the scFv of SEQ ID NO: 71 of the reference application (claim 9).
SEQ ID NO: 42 of the reference application recites the signal domain of instant SEQ ID NO: 70 required by the CARs of the instant claims and instant claims 92-93.
The CD8α hinge of instant SEQ ID NO: 72 matches the hinge in the CAR of reference SEQ ID NO: 23 and 24.
The CD8α transmembrane domain of instant SEQ ID NO: 74 matches the transmembrane domain in the CAR of reference SEQ ID NO: 24.
The 4-1BB intracellular domain of instant SEQ ID NO: 78 matches amino acids 334 to 375 of the CAR of reference SEQ ID NO: 23.
The CD3 zeta of instant SEQ ID NO: 78 is encoded by the nucleotide of SEQ ID NO: 14 which matches the CAR of SEQ ID NO: 76 (positions 1120 to 1455).
This recites all of the components of the CARs of the instant claims.
Regarding claims 22 and 42, the reference application recites a modified human T cell (claims 61-62).
Regarding claims 97-98, the reference application recites a vector comprising the polynucleotide encoding the CAR of the instant claims (claims 41-43).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant Arguments
Applicant argues, citing MPEP 1490, that if a nonstatutory double patenting rejection is the only rejection remaining and the instant application is earlier filed then the Examiner should withdraw the rejection.
Applicant cites the PTAB decision in Ex parte Baurin (Appeal 2024-002920) and states the copending application is earlier filed and cannot serve as a proper ODP reference.
Response to Arguments
Applicant's arguments filed 04/21/2026 have been fully considered but they are not persuasive.
Ex parte Baurin is a PTAB decision, which is not precedential, and thus not applicable to the instant NSDP rejection.
The NSDP rejection is proper under the guidelines of MPEP 804. The reference application and the instant application have claims to the same invention, see rejection above, and share common ownership making a double patenting rejection proper (see MPEP 804).
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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