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 .
Application Status
This action is written in response to applicant’s correspondence received 12/10/2025. Claims 1-20 are currently pending. Claims 7-9 are withdrawn from prosecution as being drawn to non-elected subject matter.
The restriction requirement mailed 6/8/2025 is still deemed proper. Applicant's elected Group I, claims 1-6 without traverse in the reply filed 8/05/2025. Claims 10-20 are new and depend from claim 1 of the elected invention. Accordingly, claims 1-6 and 10-20 are examined herein.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Priority
This application repeats a substantial portion of prior Application Nos. 18/737,778, filed 06/07/2024, 16/497,291, filed 09/24/2019 (ABN), and JAPAN 2017-061461, filed 03/27/2017.
Therefore, for the purposes of prior art, the effective filing date for the instant claims is 03/27/2017.
Specification – maintained
Note: No arguments or amendments to the specification were filed, therefore the below objection is maintained.
The use of the terms LIPOFECTAMINE™ (para 0125), RETRONECTIN® (para 0127), FLOJO™ (para 0128), and TRITON™-X (para 0134), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 3, 10, 19, and 20 are objected to because of the following informalities:
claim 3 is missing colons after the phrase “SEQ ID NO” in lines 2 and 4; and
claims 10, 19, and 20 reciting the word “isolate” should read “isolated”.
Appropriate correction is required.
Double Patenting - withdrawn
The provisional rejection of claim 1-6 under 35 U.S.C. 101 as claiming the
same invention as that of claims 2-7 of copending Application No. 18/737778
(reference application) is withdrawn because the ‘778 application was abandoned.
NSDP rejections of the previous OA mailed 8/19/2025 are withdrawn in view of Applicant’s amendment to add new claims 10-20.
Double Patenting – new necessitated by amendment
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 1-6 and 10-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11337997 in view of Iida et al. (US20090028877A1; published January 29, 2009). This new rejection is necessitated by amendment to add claims 10-20.
Claims 1-7 of U.S. Patent No. 11337997 encompass an isolated immune cell which expresses a chimeric antigen receptor targeting GM2, interleukin-7, and chemokine (C-C motif) ligand 19, where the immune cell is a T-cell, a pharmaceutical composition of the immune cell, and the immune cell comprising an expression vector containing nucleic acids encoding a receptor, IL-7 and CCL19.
Claims 1-7 of U.S. Patent No. 11337997 do not teach that the chimeric antigen receptor comprises a target antigen-binding region that includes a heavy-chain variable region and a light-chain variable region of an anti-ganglioside GM2 antibody, and wherein the anti-ganglioside GM2 antibody is comprising a first sequence having at least 95% sequence identity to SEQ ID NO: 2 and a second sequence having at least 95% sequence identity to SEQ ID NO: 4 (claims 1 and 10-20), mutations not located in CDR1, CDR2, and CDR3 (claim 2), and SEQ ID NOs: 63-68 (claim 3).
Iida’s disclosure is directed to recombinant anti-ganglioside GM2 antibody compositions having enhanced effector function useful as a medicament (abstract and para 0001). Iida further discloses antibody compositions comprising complementarity to CDR1, CDR2, and CDR3 of antibody molecule light chain variable region (SEQ ID NOs: 17-19) and heavy chain variable regions (SEQ ID NOs: 14-16) (para 0014).
Regarding claim 1, Iida teaches antibody fragments comprising a VH-P-VL or VL-P-VH polypeptide in which one VH and one VL are linked via an appropriate peptide linker (hereinafter referred to as P) and which has antigen-binding activity (para 0057). Iida further teaches several sequences having at least 95% sequence identity to Applicant’s SEQ ID NO: 2. (See alignments below for one example. Qy is SEQ ID NO: 2 and DB is SEQ ID NO: 26.)
(Applicant SEQ ID NO: 2)
Query Match 100.0%; Score 651; Length 125;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVKQSPGQGLEWMGYIYPNNGGTGY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVKQSPGQGLEWMGYIYPNNGGTGY 60
Qy 61 NQKFKSKVTITVDTSTSTAYMELHSLRSEDTAVYYCATYGHYYGYMFAYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKSKVTITVDTSTSTAYMELHSLRSEDTAVYYCATYGHYYGYMFAYWGQGTLVTVSS 120
(Iida SEQ ID NO: 26)
Iida further teaches several sequences having at least 95% sequence identity to Applicant’s SEQ ID NO: 4. (See alignments below for one example. Qy is SEQ ID NO: 4 and DB is SEQ ID NO: 31.)
(Applicant SEQ ID NO: 4)
Query Match 100.0%; Score 554; Length 108;
Best Local Similarity 100.0%;
Matches 106; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQLTQSPSSLSASPGDRVTITCSASSSVSYMHWFQQKPGKAPKLWIYSTSNLASGVPAR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQLTQSPSSLSASPGDRVTITCSASSSVSYMHWFQQKPGKAPKLWIYSTSNLASGVPAR 60
Qy 61 FSGSGSGTSYSLTISRLQPEDIATYYCQQRSSYPYTFGGGTKVEIK 106
||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSGSGTSYSLTISRLQPEDIATYYCQQRSSYPYTFGGGTKVEIK 106
(Iida SEQ ID NO: 31)
Regarding claim 2, Iida teaches mutations in regions in the heavy chain variable region and the light chain variable region, which are in regions other than CDR1, CDR2, and CDR3. Iida teaches mutations in the heavy chain region which are not in the CDR1, CDR2, and CDR3 regions. (See alignment below with CDR regions underlined. Qy is SEQ ID NO: 2 and DB is SEQ ID NO: 20.)
(Applicant SEQ ID NO: 2)
Query Match 88.6%; Score 577; DB 1; Length 120;
Best Local Similarity 86.7%;
Matches 104; Conservative 8; Mismatches 8; Indels 0; Gaps 0;
Qy 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVKQSPGQGLEWMGYIYPNNGGTGY 60
|||| ||| |: |||||||:|||||||||||||||||||| |: |||:||||||||||||
Db 1 EVQLQQSGPELVKPGASVKISCKASGYTFTDYNMDWVKQSHGKSLEWIGYIYPNNGGTGY 60
CDR1 CDR2
Qy 61 NQKFKSKVTITVDTSTSTAYMELHSLRSEDTAVYYCATYGHYYGYMFAYWGQGTLVTVSS 120
||||||| |:||| |:|||||||||| |||:||||||||||||||||||||||||||||:
Db 61 NQKFKSKATLTVDKSSSTAYMELHSLTSEDSAVYYCATYGHYYGYMFAYWGQGTLVTVSA 120
CDR2 CDR3
(Iida SEQ ID NO: 20)
Iida further teaches mutations in the light chain region which are not in the CDR1, CDR2, and CDR3 regions. (See alignment below with CDR regions underlined. Qy is SEQ ID NO: 4 and DB is SEQ ID NO: 25.)
(Applicant SEQ ID NO: 4)
Query Match 89.4%; Score 495; DB 1; Length 108;
Best Local Similarity 89.6%;
Matches 95; Conservative 5; Mismatches 6; Indels 0; Gaps 0;
Qy 1 DIQLTQSPSSLSASPGDRVTITCSASSSVSYMHWFQQKPGKAPKLWIYSTSNLASGVPAR 60
|||:|||||||||| |||||||||||||||||||:|||||||||| ||||||||||||:|
Db 1 DIQMTQSPSSLSASVGDRVTITCSASSSVSYMHWYQQKPGKAPKLLIYSTSNLASGVPSR 60
CDR1 CDR2
Qy 61 FSGSGSGTSYSLTISRLQPEDIATYYCQQRSSYPYTFGGGTKVEIK 106
|||||||| ::|||| ||||| |||||||||||||||| |||||||
Db 61 FSGSGSGTDFTLTISSLQPEDFATYYCQQRSSYPYTFGQGTKVEIK 106
CDR3
(Iida SEQ ID NO: 25)
Regarding claim 3, Iida teaches antibody compositions comprising complementarity to CDR1, CDR2, and CDR3 of antibody molecule light chain variable region and heavy chain variable regions (para 0014). Iida further teaches SEQ ID NO: 20 having 100% sequence identity to Applicant’s SEQ ID NO: 63 encoding heavy chain.
(Applicant’s SEQ ID NO: 63)
Qy 1 DYNMD 5
|||||
Db 31 DYNMD 35
(Iida SEQ ID NO: 20)
Iida teaches SEQ ID NO: 15 having 100% sequence identity to Applicant’s SEQ ID NO: 64 encoding heavy chain.
(Applicant’s SEQ ID NO: 64)
Qy 1 YIYPNNGGTGYNQKFKS 17
|||||||||||||||||
Db 1 YIYPNNGGTGYNQKFKS 17
(Iida SEQ ID NO: 15)
Iida teaches SEQ ID NO: 20 having 100% sequence identity to Applicant’s SEQ ID NO: 65 encoding heavy chain.
(Applicant’s SEQ ID NO: 65)
Qy 1 YGHYYGYMFAY 11
|||||||||||
Db 99 YGHYYGYMFAY 109
(Iida SEQ ID NO: 20)
Iida teaches SEQ ID NO: 17 having 100% sequence identity to Applicant’s SEQ ID NO: 66 encoding light chain.
(Applicant’s SEQ ID NO: 66)
Qy 1 SASSSVSYMH 10
||||||||||
Db 1 SASSSVSYMH 10
(Iida SEQ ID NO: 17)
Iida teaches SEQ ID NO: 18 having 100% sequence identity to Applicant’s SEQ ID NO: 67 encoding light chain.
(Applicant’s SEQ ID NO: 67)
Qy 1 STSNLAS 7
|||||||
Db 1 STSNLAS 7
(Iida SEQ ID NO: 18)
Iida teaches SEQ ID NO: 19 having 100% sequence identity to Applicant’s SEQ ID NO: 68 encoding light chain.
(Applicant’s SEQ ID NO: 68)
Qy 1 QQRSSYPYT 9
|||||||||
Db 1 QQRSSYPYT 9
(Iida SEQ ID NO: 19)
It would have been obvious to one of ordinary skill in the art to have modified the immune cell of U.S. Patent No. 11337997 expressing a receptor targeting GM2 to specifically include a heavy-chain variable region and a light-chain variable region and to further comprise SEQ ID NOs: 2 and 4, and 63-68 as taught in Iida because it would have amounted to a simple combinations of prior art elements according to known methods to yield predictable results. One would have had a reasonable expectation of success because U.S. Patent No. 11337997 and Iida are directed to immunotherapy with engineered immune cells comprising a receptor targeting GM2 to treat tumors and diseases. Thus, the claimed invention as a whole is prima facie obvious.
Claims 1-6 and 10-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11931381 in view of Iida et al. (US20090028877A1; published January 29, 2009). This new rejection is necessitated by amendment to add claims 10-20.
Claims 1-20 of U.S. Patent No. 11931381 encompass an isolated immune cell which expresses a chimeric antigen receptor targeting GM2, interleukin-7, and chemokine (C-C motif) ligand 19, where the immune cell is a T-cell, and a pharmaceutical composition of the immune cell.
Claims 1-20 of U.S. Patent No. 11931381 do not teach that the chimeric antigen receptor comprises a target antigen-binding region that includes a heavy-chain variable region and a light-chain variable region of an anti-ganglioside GM2 antibody, and wherein the anti-ganglioside GM2 antibody is comprising a first sequence having at least 95% sequence identity to SEQ ID NO: 2 and a second sequence having at least 95% sequence identity to SEQ ID NO: 4 (claims 1 and 10-20), mutations not located in CDR1, CDR2, and CDR3 (claim 2), and SEQ ID NOs: 63-68 (claim 3).
However, the teachings of Iida are discussed above. In particular, the teachings of Iida regarding SEQ ID NOs: 2 and 4 (claim 1), mutations not located in CDR1, CDR2, and CDR3 (claim 2), and SEQ ID NOs: 63-68 (claim 3) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the immune cell of U.S. Patent No. 11931381 expressing a receptor targeting GM2 to specifically include a heavy-chain variable region and a light-chain variable region and to further comprise SEQ ID NOs: 2 and 4, and 63-68 as taught in Iida because it would have amounted to a simple combinations of prior art elements according to known methods to yield predictable results. One would have had a reasonable expectation of success because U.S. Patent No. 11931381 and Iida are directed to immunotherapy with engineered immune cells comprising a receptor targeting GM2 to treat tumors and diseases. Thus, the claimed invention as a whole is prima facie obvious.
Claims 1-6 and 10-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18424245 in view of Iida et al. (US20090028877A1; published January 29, 2009). This new rejection is necessitated by amendment to add claims 10-20.
Claims 1-10 of the ‘245 application encompass an isolated immune cell which expresses a chimeric antigen receptor targeting GM2, interleukin-7, and chemokine (C-C motif) ligand 19, where the immune cell is a T-cell, a pharmaceutical composition of the immune cell, and the immune cell comprising an expression vector containing nucleic acids encoding a receptor, IL-7 and CCL19.
Claims 1-10 of the ‘245 application do not teach that the chimeric antigen receptor comprises a target antigen-binding region that includes a heavy-chain variable region and a light-chain variable region of an anti-ganglioside GM2 antibody, and wherein the anti-ganglioside GM2 antibody is comprising a first sequence having at least 95% sequence identity to SEQ ID NO: 2 and a second sequence having at least 95% sequence identity to SEQ ID NO: 4 (claims 1 and 10-20), mutations not located in CDR1, CDR2, and CDR3 (claim 2), and SEQ ID NOs: 63-68 (claim 3).
However, the teachings of Iida are discussed above. In particular, the teachings of Iida regarding SEQ ID NOs: 2 and 4 (claim 1), mutations not located in CDR1, CDR2, and CDR3 (claim 2), and SEQ ID NOs: 63-68 (claim 3) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the immune cell of the ‘245 application expressing a receptor targeting GM2 to specifically include a heavy-chain variable region and a light-chain variable region and to further comprise SEQ ID NOs: 2 and 4, and 63-68 as taught in Iida because it would have amounted to a simple combinations of prior art elements according to known methods to yield predictable results. One would have had a reasonable expectation of success because the ‘245 application and Iida are directed to immunotherapy with engineered immune cells comprising a receptor targeting GM2 to treat tumors and diseases. Thus, the claimed invention as a whole is prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 12/10/2025 have been fully considered but they are not persuasive. Applicant argues that the POSITA would not have been motivated to make the proposed combinations of the primary references with Iida because the antibody used in lida has the same amino acid sequence in its Complementarity-Determining Region ("CDR") as antibody BIW-8962 and that antibody BIW-8962, when tested for treatment multiple myeloma, failed to show any efficacy in a clinical trial. Applicant further argues that the study was prematurely terminated at Phase la of a Phase 1/2 study design "due to a lack of efficacy." Applicant further argues that the amino acid sequence of the CDR region from BIW-8962-001 is identical to the CDR of KM8969, (see Appx 1, 289, left column ("Preclinical studies employed a precursor mAb, KM8969, with the same complementarity-determining regions as BIW-8962."), which in turn is identical to the CDR disclosed in lida. See Appendix 2, (JP4550947 at claims 7 and 8 showing SEQ ID NO: 77 corresponding to the heavy chain variable region sequence of KM8969 and SEQ ID NO: 78 corresponding to the light chain variable region sequence of KM8969), Appendix 3 (alignment of SEQ ID NO: 77 from JP4550947 with the claimed SEQ ID NO 26 of lida, and alignment of SEQ ID NO: 78 from JP4550947 with the claimed SEQ ID NO: 31 of lida). Applicant argues that Appendix 4 shows that BIW-8962 was also tested for its efficacy in lung cancer treatment but the study was also terminated due to lack of efficacy. Finally, applicant argues that given the lack of efficacy of the claimed antibody in treating multiple types of cancer, a POSITA would not have been motivated to select the antibody of lida with any of the cited primary references and further argues that, to the contrary, given the lack of efficacy, a POSITA would have refrained from using the antibody of lida.
The Office disagrees. The Office acknowledges that these two studies using different antibodies (sharing amino acid sequences) KM8969 to treat multiple myeloma and BIW-8962 to treat lung cancer failed to successfully treat cancer in each case. The examples given by Applicant are specific to only two different types of cancer, but the lack of efficacy is being erroneously applied to all types of cancer.
Yano et al. (US20140220003A1; published 8/7/2014) teaches KM8969 to treat mesothelioma and Shitara et al. (US20110236374A1; published 9/29/2011) teaches that KM8969 can be used to treat other cancers, including thymic lymphoma, B cell lymphoma, T cell lymphoma, melanoma, osteosarcoma, acute T-cell leukemia, small cell lung cancer, neuroblastoma, and glioblastoma.
Therefore, one would not have been discouraged from modifying the immune cells of the references expressing a receptor targeting GM2 to specifically include a heavy-chain variable region and a light-chain variable region and to further comprise SEQ ID NOs: 2 and 4, and 63-68 as taught in Iida because it would have amounted to a simple combinations of prior art elements according to known methods to yield predictable results of treating different types of cancer. Accordingly, the rejections are maintained.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached Monday - Friday 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636