DETAILED ACTION
This action is in reply to papers filed 7/30/3026.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20250333758A1, Published 10/30/2025.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-10 and 17-18) in the reply filed on 7/30/206 is acknowledged. The traversal is on the ground(s) that no undue burden is imposed on the Examiner by the prosecution of all pending claims. Upon reconsideration, Applicant’s arguments have been found persuasive, and the restriction requirement between Group I and Group II is withdrawn.
Accordingly, claims 1-18 are pending and examined herein.
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 1-2, 5-6, 9-11, 14 and 17 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.
Each of claims 1-2, 5-6, 9-11, 14 and 17 recite the phrase "preferably". Recitation of such language renders the claim indefinite because it is unclear whether the limitations following the phrase are mandatory limitations or purely optional. See MPEP § 2173.05(d).
Claim 13 recites, inter alia, “or the modified cell”. There is no antecedent basis for this limitation. Note that limitations drawn to a modified cell have been cancelled in claim 11.
Appropriate correction is requested.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Prior Art Rejection 1
Claim(s) 1,6,9-12 and 14-15 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Siler et al. (US20230227847A1, Filed 4/7/2021;).
Siler is drawn to use of AAV vectors (Pg. 40,para. 603), host cells or pharmaceutical composition for use in the treatment of brain tumors (as in claim 11 and claim 14), particularly brain tumors selected from the group consisting of glioblastoma, glioma (as in claim 12 and claim 15) , ganglioneuroblastoma, astrocytoma, oligodendroglioma, PNET (primitive neuroectodermal), medulloblastoma, CNS lymphoma, and neuroblastoma, or any other CNS tumor and further in the treatment of brain metastasis, originating from any form of solid tumor (Pg. 44,para. 688). Siler discloses the invention is based on the surprising identification of promoters that can drive expression of a transgene in myeloid cells and microglia (as in claim 9) (Pg. 1, para. 15). Siler teaches the transgene preferably encodes one or more therapeutic protein, such as the antigen-binding molecule may be a chimeric antigen receptor (CAR) (Pg. 12, para. 150). Siller teaches the AAV vectors (as in claim 1), host cells (as in claim 6 and claim 10) and pharmaceutical compositions comprise the CAR (Pg. 43, para. 669; Pg. 12, para. 143-146).
Accordingly, Siler anticipates the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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.
Prior Art Rejection 2
Claim(s) 4-5, 7-8, 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Siler et al. (US20230227847A1, Filed 4/7/2021) as applied to claims 1,6,9-12 and 14-15 and further in view of Perera et al. (PgPub US20190233526A1, Published 8/1/2019), June et al. (PgPub US20180256712A1, Published 9/13/2018), Juillerat et al. (WO2015092024A2, Published 8/13/2015) and June et al. (WO2012079000A1, Published 8/23/2012), hereinafter referred to as June (b).
The teachings of Siler et al. are relied upon as detailed above. However, Siler fails to teach the CAR comprises, from N terminus to C- terminus: an antigen-binding domain which specifically binds to the tumor cell; a hinge domain; a transmembrane domain; and an intracellular signaling domain (as in claim 4).
Before the effective filing date of the claimed invention, Lee et al. taught a chimeric antigen receptor is disclosed that includes: (a) an scFv comprising a light chain variable domain (VL) and a heavy chain variable domain (VH), wherein the scFv specifically binds to a tumor antigen; (b) a hinge and transmembrane domain from CD8; (c) an intracellular 4-1BB signaling domain; and (d) an intracellular CD3 zeta signaling domain, wherein (a)-(d) are in N to C terminal order (as in claim 4 and claim 7) (Abstract). Lee teaches such CARs, in a composition, can be administered to a patient intratumorally (as in claim 13 and claim 16) (Pg. 22, para. 199).
However neither Lee et al. nor Siler et al. teach the antigen-binding domain specifically binds to a biomarker as listed in claim 5 or 8, a transmembrane domain listed in claim 5 or 8, or an intracellular signaling domain as listed in claim 5 or 8.
Before the effective filing date of the claimed invention, June et al. taught a method of treating cancer in a patient (Abstract), specifically solid tumors (Pg. 3, para. 31), comprising administering to the patient an effective amount of T cells genetically modified to express a chimeric antigen receptor (“CAR”), wherein the CAR comprises CD19 antigen binding domain, human CD8a hinge and transmembrane domain, and human 4-1BB and CD3zeta signaling domains (as in claim 5(in-part) and claim 8) (Pg. 7, para. 91).
And although June et al. teach CD8a hinge and transmembrane domain, June fails to teach SEQ ID NO: 44 (as further in claim 5).
Before the effective filing date of the claimed invention, Juillerat taught a CD8 alpha transmembrane domain that is 100% identical to SEQ ID NO: 44 (as further in claim 5). The alignment between SEQ ID NO: 44 and the CD8 alpha transmembrane domain taught by is copied below.
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And although June et al. teach 4-1 BB, June fails to teach SEQ ID NO: 45 (as further in claim 5).
Before the effective filing date of the claimed invention, June (b) taught a 4-1BB signaling domain that is 100% identical to SEQ ID NO: 45 (as further in claim 5). The alignment between SEQ ID NO: 45 and the 4-1BB signaling domain taught by June (b) is copied below.
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And although June et al. teach intracellular CD3 zeta signaling domain, June fails to teach SEQ ID NO: 46 (as further in claim 5).
Before the effective filing date of the claimed invention, June (b) taught an intracellular CD3 zeta signaling domain that is 100% identical to SEQ ID NO: 46 (as further in claim 5). The alignment between SEQ ID NO: 46 and the intracellular CD3 zeta signaling domain taught by June (b) is copied below.
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The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Siler et al., wherein Siler teaches a method of treating a solid brain tumor, comprising administering a pharmaceutical composition comprising an AAV vector comprising a CAR , with the teachings of Lee et al., wherein Lee taught a CAR comprising a tumor antigen domain; (b) a hinge and transmembrane domain from CD8; (c) an intracellular 4-1BB signaling domain; and (d) an intracellular CD3 zeta signaling domain, wherein (a)-(d) are in N to C terminal order, with a reasonable expectation of arriving at the claimed invention. The skilled artisan would have found it prima facie obvious to do so because Perera teaches this composition finds use in treating CNS tumors. As such, the artisan of ordinary skill would have found it prima facie obvious to select the specific sequences of the hinge and transmembrane domain from CD8, the intracellular 4-1BB signaling domain; and the intracellular CD3 zeta signaling domain, as set forth in Scholler and June (b), given the teachings of Perera.
Thus, the combination would have been prima facie obvious.
Prior Art Rejection 3
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Siler et al. (US20230227847A1, Filed 4/7/2021; Ref. 2 in IDS filed 6/17/2024) as applied to claims 1,6,9-12 and 14-15 and further in view of Wilson et al. (WO2000028061A2, Published 5/18/2000)
The teachings of Siler et al. are relied upon as detailed above. However, Siler fails to teach the rAAV comprises a VP1 capsid protein having an amino acid sequence selected from a group consisting of SEQ ID NOs: 25-30 and SEQ ID NO: 32-42, or an amino acid sequence having at least 85%, 90%, 95, 98% or 99% sequence identity thereof (as in claim 18).
Before the effective filing date of the claimed invention, Wilson taught an AAV serotype 1 capsid protein VP1 that is 98% identical to SEQ ID NO: 25 (as in claim 18). The alignment between SEQ ID NO: 25 and the VP1 capsid protein taught by Wilson is copied below.
RESULT 16
AAY71167
(NOTE: this sequence has 405 duplicates in the database searched.
See complete list at the end of this report)
ID AAY71167 standard; protein; 736 AA.
XX
AC AAY71167;
XX
DT 15-JUN-2007 (revised)
DT 08-SEP-2000 (first entry)
XX
DE Adeno-associated virus serotype 1 capsid protein VP1.
XX
KW Adeno-associated virus serotype 1; AAV-1; rep protein; capsid protein;
KW cap protein; recombinant viral vector; gene delivery; gene therapy;
KW vaccine; transgene; VP1; BOND_PC; capsid protein;
KW capsid protein [adeno-associated virus 1]; GO5198; GO19028; GO6959.
XX
OS Adeno-associated virus 1.
XX
CC PN WO200028061-A2.
XX
CC PD 18-MAY-2000.
XX
CC PF 02-NOV-1999; 99WO-US025694.
XX
PR 05-NOV-1998; 98US-0107114P.
XX
CC PA (UYPE-) UNIV PENNSYLVANIA.
XX
CC PI Wilson JM, Xiao W;
XX
DR WPI; 2000-376571/32.
DR N-PSDB; AAD00772, AAD00777.
DR PC:NCBI; gi9632548.
XX
CC PT Novel adeno-associated virus serotype 1 polynucleotide useful for
CC PT preparation of medicament for delivery of a transgene to a host.
XX
CC PS Claim 7; Page 87-90; 108pp; English.
XX
CC The patent discloses an adeno-associated virus serotype 1 (AAV-1) DNA
CC which is characterised by two inverted terminal repeats (ITR) and open
CC reading frames for rep and capsid (cap) proteins. The rep reading frame
CC encodes four proteins, Rep 78, Rep 68, Rep 52 and Rep 40, while the cap
CC reading frame encodes three structural proteins, VP1, VP2 and VP3. The
CC AAV-1 sequence or its fragments particularly ITRs, rep and cap coding
CC regions, are useful in production of recombinant viral vectors for gene
CC delivery. These vectors can be used as gene therapy vectors, vaccine
CC vectors or antisense delivery vectors. The AAV-1 does not induce the
CC formation of neutralising antibodies specific to any serotype of AAV
CC hence is useful for transforming host cells, and in the preparation of a
CC medicament for the delivery of transgene to a host. The present sequence
CC is an AAV-1 cap protein VP1 which is useful in the production of
CC recombinant viral vector for gene delivery
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 736 AA;
Query Match 98.7%; Score 3975.5; Length 736;
Best Local Similarity 99.1%;
Matches 736; Conservative 0; Mismatches 0; Indels 7; Gaps 1;
Qy 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPLGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPLGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSE 180
Qy 181 SVPDPQPLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
Qy 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
Qy 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEEVP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEEVP 420
Qy 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
Qy 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
Qy 541 MIFGKESAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNFQSSSTDPVNMHTRPAT 600
|||||||||||||||||||||||||||||||||||||||||||||||||| |||
Db 541 MIFGKESAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNFQSSSTD-------PAT 593
Qy 601 GDVHAMGALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKNPPPQILIKNTP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 594 GDVHAMGALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKNPPPQILIKNTP 653
Qy 661 VPANPPAEFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDF 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 654 VPANPPAEFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDF 713
Qy 721 TVDNNGLYTEPRPIGTRYLTRPL 743
|||||||||||||||||||||||
Db 714 TVDNNGLYTEPRPIGTRYLTRPL 736
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Siler et al., wherein Siler teaches a method of treating a solid brain tumor, comprising administering a pharmaceutical composition comprising an AAV vector comprising a CAR, with the teachings of Wilson et al., wherein Wilson teaches an AAV serotype 1 capsid protein VP1 that is useful in the field of gene therapy, with a reasonable expectation of arriving at the claimed invention. It would have been prima facie obvious to use the AAV vector of Wilson given Wilson’s teachings regarding its suitability in gene therapy.
Thus, the combination would have been prima facie obvious.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632
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