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 .
Priority
The effective filing date is 03 May 2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05 December 2024 and 03 May 2023 are being considered by the examiner.
Status of Application, Amendments, and/or Claims
Claims 1-20 are the original claims filed on 03 May 2023. Claims 1-20 are pending and the subject of this office action.
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 1-20 are rejected under 35 U.S.C. 102 (a1) and (a2) as being anticipated by US 2021/0244759 A1 (herein Gross), which is related to a reference cited, WO2019/068007 A1, in the information disclosure statements (IDS) submitted on 05 December 2024.
Regarding claims 1, 4, 6, 8, 12, and 14, Gross teaches a method for treating cancer in a subject having a tumor characterized by a loss of heterozygosity. The method involves administering activating chimeric antigen receptors, recognizing antigens expressed on the surface of tumor cells, inhibitory CARs and protective CARs directed at allelic variants of the same or other cell surface antigens expressed by normal cells but not by the tumor due to loss of heterozygosity ([0055], [0143]-[0145], and figures 1 and 2). In multiple examples an anti-CD19 CAR is used as an activating CAR ([0769] and [0787]). Gross discloses the nucleic acid, SEQ ID NO:1, that was used to encodes the amino acid sequence comprising an anti-CD19 chimeric antigen receptor (SEQ ID NO: 2) ([0797] and figure 21). The amino acid disclosed shares 100% amino acid sequence identity with SEQ ID NO: 17 of the instant application, referenced in instant claim 14. Additionally, this sequence comprises limitations established in instant claims 1, 3, 4, 6, 8, 12, and 14:
An anti-CD19 binding domain (instant claim 4, SEQ ID NO: 9) comprising:
A heavy chain variable region (claim 3, SEQ ID NO: 7) comprising:
CDR1 (instant claim 1, SEQ ID NO: 1)
CDR2 (instant claim 1, SEQ ID NO: 2)
CDR3 (instant claim 1, SEQ ID NO: 3)
A light chain variable region (claim 3, SEQ ID NO: 8) comprising:
CDR1 (instant claim 1, SEQ ID NO: 4)
CDR2 (instant claim 1, SEQ ID NO: 5)
CDR3 (instant claim 1, SEQ ID NO: 6)
A 4-1BB costimulatory domain (instant claims 1 and 6, SEQ ID NO: 13) ([0149])
A CD3 zeta intracellular signaling domain (instant claims 1 and 8, SEQ ID NO: 15) ([0284])
A CD8 hinge (instant claim 12, SEQ ID NO: 12) ([0763]).
[AltContent: connector] Anti-CD19 binding domain
CDRL1
Ref MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQK 60
Instant ---------------------DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQK 39
***************************************
Anti-CD19 binding domain [AltContent: connector]
CDRL2 CDRL3
Ref PDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFG 120
Instant PDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFG 99
************************************************************
Anti-CD19 binding domain [AltContent: connector]
CDRH1
Ref GGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWI 180
Instant GGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWI 159
************************************************************
CDRH2
Ref RQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAK 240
Instant RQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAK 219
************************************************************
[AltContent: connector] Anti-CD19 binding domain
CDRH3 CD8 hinge
Ref HYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT 300
Instant HYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT 279
************************************************************
CD8 hinge 4-1BB
Ref RGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC 360
Instant RGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGC 339
************************************************************
4-1BB | CD3 zeta
Ref SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMG 420
Instant SCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMG 399
************************************************************
CD3 zeta
Ref GKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM 480
Instant GKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHM 459
************************************************************
CD3 zeta
Ref QALPPR 486
Instant QALPPR 465
******
Regarding claims 1, 5, 7, 9, 13, and 15, Gross teaches a nucleic acid that encodes a murine anti-CD19 chimeric antigen receptor ([0797], figure 21, and SEQ ID NO: 1). This nucleic acid comprises a sequence that shares 100% sequence identity with SEQ ID NO: 18 of instant claim 15 (see alignment below). The sequence described in SEQ ID NO: 15 of the instant application and SEQ ID NO: 1 of the reference encodes a murine anti-CD19 chimeric antigen receptor, which satisfies all the limitations of claim 1 (see rejections of claims 1, 4, 6, 8, 12, and 14, above). Additionally, this nucleic acid comprises sequence limitations established in instant claims 5 (SEQ ID NO: 10), 7 (SEQ ID NO: 14), 9 (SEQ ID NO: 16), and 13 (SEQ ID NO: 12).
Instant ------------------------------------------------------------ 0
Ref atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccagg 60
anti-CD19 binding domain
Instant ---gacatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtc 57
Ref ccggacatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtc 120
*********************************************************
anti-CD19 binding domain
Instant accatcagttgcagggcaagtcaggacattagtaaatatttaaattggtatcagcagaaa 117
Ref accatcagttgcagggcaagtcaggacattagtaaatatttaaattggtatcagcagaaa 180
************************************************************
anti-CD19 binding domain
Instant ccagatggaactgttaaactcctgatctaccatacatcaagattacactcaggagtccca 177
Ref ccagatggaactgttaaactcctgatctaccatacatcaagattacactcaggagtccca 240
************************************************************
anti-CD19 binding domain
Instant tcaaggttcagtggcagtgggtctggaacagattattctctcaccattagcaacctggag 237
Ref tcaaggttcagtggcagtgggtctggaacagattattctctcaccattagcaacctggag 300
************************************************************
anti-CD19 binding domain
Instant caagaagatattgccacttacttttgccaacagggtaatacgcttccgtacacgttcgga 297
Ref caagaagatattgccacttacttttgccaacagggtaatacgcttccgtacacgttcgga 360
************************************************************
anti-CD19 binding domain
Instant ggggggaccaagctggagatcacaggtggcggtggctcgggcggtggtgggtcgggtggc 357
Ref ggggggaccaagctggagatcacaggtggcggtggctcgggcggtggtgggtcgggtggc 420
************************************************************
anti-CD19 binding domain
Instant ggcggatctgaggtgaaactgcaggagtcaggacctggcctggtggcgccctcacagagc 417
Ref ggcggatctgaggtgaaactgcaggagtcaggacctggcctggtggcgccctcacagagc 480
************************************************************
anti-CD19 binding domain
Instant ctgtccgtcacatgcactgtctcaggggtctcattacccgactatggtgtaagctggatt 477
Ref ctgtccgtcacatgcactgtctcaggggtctcattacccgactatggtgtaagctggatt 540
************************************************************
anti-CD19 binding domain
Instan cgccagcctccacgaaagggtctggagtggctgggagtaatatggggtagtgaaaccaca 537
Ref cgccagcctccacgaaagggtctggagtggctgggagtaatatggggtagtgaaaccaca 600
************************************************************
anti-CD19 binding domain
Instant tactataattcagctctcaaatccagactgaccatcatcaaggacaactccaagagccaa 597
Ref tactataattcagctctcaaatccagactgaccatcatcaaggacaactccaagagccaa 660
************************************************************
anti-CD19 binding domain
Instant gttttcttaaaaatgaacagtctgcaaactgatgacacagccatttactactgtgccaaa 657
Ref gttttcttaaaaatgaacagtctgcaaactgatgacacagccatttactactgtgccaaa 720
************************************************************
anti-CD19 binding domain
Instant cattattactacggtggtagctatgctatggactactggggccaaggaacctcagtcacc 717
Ref cattattactacggtggtagctatgctatggactactggggccaaggaacctcagtcacc 780
************************************************************
CD8 Hinge
Instant gtctcctcaACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCC 777
Ref gtctcctcaACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCC 840
************************************************************
CD8 Hinge
Instant CAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACC 837
Ref CAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACC 900
************************************************************
CD8 Hinge
Instant CGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGG 897
Ref CGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGG 960
************************************************************
CD8 Hinge 4-1BB
Instant GTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTaagcgcggtcggaagaagctgctg 957
Ref GTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTaagcgcggtcggaagaagctgctg 1020
************************************************************
4-1BB
Instant tacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgt 1017
Ref tacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgt 1080
************************************************************
4-1BB CD3 Zeta
Instant tcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgc 1077
Ref tcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgc 1140
************************************************************
CD3 Zeta
Instant agcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatctt 1137
Ref agcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatctt 1200
************************************************************
CD3 Zeta
Instant ggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc 1197
Ref ggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc 1260
************************************************************
CD3 Zeta
Instant gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataag 1257
Ref gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataag 1320
************************************************************
CD3 Zeta
Instant atggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac 1317
Ref atggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac 1380
************************************************************
CD3 Zeta
Instant gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatg 1377
Ref gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatg 1440
************************************************************
CD3 Zeta
Instant caggccctgccgcctcgg------------------------------------------ 1395
Ref caggccctgccgcctcggtgagcggccgcaaattccgcccctctccctccccccccccta 1500
******************
Regarding claim 2, Gross teaches a nucleic acid encoding a murine anti-CD19 chimeric antigen receptor, as discussed for claim 15. The encoded CAR element comprises an anti-CD19 scFv ([0006], [0191], [0263], [0442], and [0797]).
Regarding claims 10 and 11, Gross teaches a nucleic acid, reference SEQ ID NO:1, sequentially comprising a murine anti-CD19 chimeric antigen receptor with a single chain antibody fragment (anti-CD19 binding domain), a costimulatory domain (4-1BB), a primary intracellular signaling domain (CD3 zeta), and a CD8 hinge (CD8 hinge) as illustrated by the annotated amino acid sequence shown above ([0284], [0763], and [0149]).
Regarding claims 16-18, Gross teaches a vector comprising the nucleic acid encoding an anti-CD19 CAR, in which the vector may be a plasmid, cosmid, or virus ([0123]). Gross further teaches that the vector may comprise an EF1 promoter ([0278]).
Regarding claims 19 and 20, Gross teaches the engineering of cells with the described vectors, which includes T-cells, natural killer cells, or cytokine-induced killer cells ([0312] and [0313]).
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW CURRAN METCALF whose telephone number is (571)272-5520. The examiner can normally be reached 7:30AM-5:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MATTHEW CURRAN METCALF/ Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647