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 .
DETAILED ACTION
The amendment filed November 17, 2025, is acknowledged and has been entered. Claims 152, 163-165, 167-169, 172-173 and 175 have been amended. Claims 153, 166, 174 and 177-178 have been canceled. Claims 179-182 have been newly added.
Claims 152, 154-165, 167-173, 175-176 and 179-182 are pending in the application and are under examination.
Grounds of Rejection Withdrawn
Applicant's amendment has obviated or rendered moot the grounds of rejection set forth in the previous 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 152, 154-158, 160-161, 163, 171-173 and 175-176 are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by Morgan et al (WO 2016/094304 A1) as evidenced by Wang et al (WO 2016/149254 A1, of record) and Zhang et al (WO 2018/200586 A1, of record).
With respect to claim 152, Morgan et al disclose compositions comprising chimeric polypeptides (chimeric antigen receptors, CARs) comprising, in an order from N-terminal to C terminal: an antigen binding domain, a hinge domain and a transmembrane domain, and a cytoplasmic signaling domain, wherein the hinge domain is a CD28 hinge domain and, wherein the cytoplasmic signaling domain comprises a CD2 signaling domain and a CD3ζ activating domain (see pages 2-4, 26 and 28, claims and Figures). With respect to claim 155, the cytoplasmic signaling domain can further comprise a CD27 co-stimulatory domain (see page 28). With respect to claims 156-158, 160 and 163, the antigen binding domain can be an scFv and can be specific for the tumor associated antigen of BCMA or CD19, while the transmembrane domain can be a CD28 transmembrane domain. (see pages 2-4, 10). With respect to claims 171-173, Morgan et al disclose polynucleotides encoding the chimeric polypeptides and the polynucleotide and chimeric polypeptide in T cells or autologous T cells (see pages 38, 69 and 75). With respect to claims 175-176, Morgan et al disclose treating cancer (a hyperproliferative disorder) by administering such cells (see page 4 and claim 35). While Morgan et al is silent with respect to CD58 expression, claim 176 does not require detecting CD58 expression or selecting such a patient and the cancers of Morgan et al necessarily include hyperproliferative disorders having the properties of claim 176.
Then with respect to claim 154, while Morgan et al is silent about the sequence of CD2, as evidenced by Wang et al (see alignment below), the CD2 intracellular sequence is 100% identical to instant SEQ ID NO:8, so the CD2 intracellular domain of Morgan et al is the same as that of instant claim 154.
RESULT 1
BDE76810
(NOTE: this sequence has 60 duplicates in the database searched.
See complete list at the end of this report)
ID BDE76810 standard; protein; 116 AA.
XX
AC BDE76810;
XX
DT 03-NOV-2016 (first entry)
XX
DE CAR preparing CD2 protein fragment (residues 236-351), SEQ ID 28.
XX
KW CD2 protein; Lymphocyte function antigen-3 receptor; antimicrobial-gen.;
KW bacterial infection; cancer; cytostatic; fungal infection;
KW gene regulation; infectious disease; protozoal infection; therapeutic;
KW viral infection.
XX
OS Unidentified.
XX
CC PN WO2016149254-A1.
XX
CC PD 22-SEP-2016.
XX
CC PF 15-MAR-2016; 2016WO-US022442.
XX
PR 17-MAR-2015; 2015US-0134143P.
PR 24-APR-2015; 2015US-0152727P.
PR 23-JUN-2015; 2015US-0183595P.
PR 08-JAN-2016; 2016US-0276449P.
XX
CC PA (CHIM-) CHIMERA BIOENGINEERING INC.
XX
CC PI Wang B, Zeiner G;
XX
DR WPI; 2016-59574R/68.
DR REFSEQ; NP_001758.2.
XX
CC PT New nucleic acid comprising a polynucleotide encoding a Chimeric Antigen
CC PT Receptor (CAR), useful for making a eukaryotic cell used for treating
CC PT cancer or an infectious disease.
XX
CC PS Disclosure; SEQ ID NO 28; 108pp; English.
XX
CC The present invention relates to a novel nucleic acid comprising a
CC polynucleotide operably linked to a polynucleotide encoding a chimeric
CC antigen receptor (CAR). The CAR comprises an extracellular element, a
CC transmembrane element, and an intracellular element, wherein the
CC transmembrane element is between the extracellular element and the
CC intracellular element. The invention further claims: (1) an eukaryotic
CC cell comprising the nucleic acid; (2) a method for treating cancer or a
CC disease caused by a pathogens (including a virus, a bacteria, a
CC protozoan, or a fungus) in a subject; (3) a method for controlling
CC proliferation of a T-lymphocyte; (4) a method for controlling the
CC expression of a CAR in an eukaryotic cell; (5) a method for controlling
CC an activation of a T-lymphocyte; and (6) a method for improving a RNA
CC control device by providing a virus. The eukaryotic cell is useful for
CC treating cancer or an infectious disease. The present sequence is a CD2
CC peptide used as an intracellular element for preparing the CAR.
XX
SQ Sequence 116 AA;
Query Match 100.0%; Score 644; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 KRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSH 60
Qy 61 RPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN 116
Then with respect to claim 161, while Morgan et al is silent about the sequence of CD28 transmembrane domain, as evidenced by Zhang et al (see alignment below), the CD28 transmembrane sequence is 100% identical to instant SEQ ID NO:6, so the CD28 transmembrane domain of Morgan et al is the same as that of instant claim 161.
RESULT 2
BFT70250
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BFT70250 standard; protein; 110 AA.
XX
AC BFT70250;
XX
DT 27-DEC-2018 (first entry)
XX
DE CD28 transmembrane/intracellular signaling domain fusion protein SEQ 530.
XX
KW CD28 protein; T cell surface glycoprotein CD28; antibody production;
KW antibody therapy; cancer; choriocarcinoma; cytostatic; diagnostic test;
KW fusion protein; hepatoblastoma; hepatocellular carcinoma;
KW immuno-diagnosis; immunotherapy; liposarcoma; lung tumor; melanoma;
KW nephroblastoma; neuroblastoma; ovary tumor; protein detection;
KW recombinant protein; squamous cell carcinoma; stomach tumor;
KW testis tumor; therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2018200586-A1.
XX
CC PD 01-NOV-2018.
XX
CC PF 24-APR-2018; 2018WO-US029221.
XX
PR 26-APR-2017; 2017US-0490586P.
XX
CC PA (EURE-) EUREKA THERAPEUTICS INC.
XX
CC PI Zhang P, Xu Y, Morales J, Nakano Y, Liu H, Xiang J, Acker T;
XX
DR WPI; 2018-85622A/76.
XX
CC PT New isolated anti-glypican 3 (GPC3) construct comprises an antibody
CC PT moiety specifically recognizing a cell surface-bound GPC3, for treating
CC PT and diagnosing individual having GPC3-positive disease, e.g. melanoma or
CC PT neuroblastoma.
XX
CC PS Example 8; SEQ ID NO 530; 425pp; English.
XX
CC The present invention relates to a novel isolated anti-glypican 3 (GPC3)
CC construct (chimeric antigen receptor (CAR)) comprising an antibody moiety
CC specifically recognizing a cell surface-bound GPC3, useful for treating
CC and diagnosing individual having GPC3-positive disease. The invention
CC also provides: an isolated nucleic acid encoding the polypeptide
CC components of the isolated anti-GPC3 construct; a vector comprising the
CC isolated nucleic acid; an effector cell expressing the isolated anti-GPC3
CC construct; a kit comprising the isolated anti-GPC3 construct, the
CC isolated nucleic acid, the vector, the isolated host cell, the effector
CC cell, or the pharmaceutical composition; a method for detecting GPC3 in a
CC sample; a method for treating an individual having GPC3-positive disease;
CC a method for diagnosing an individual having GPC3-positive disease; and a
CC method for producing an isolated anti-GPC3 construct. The GPC3-positive
CC disease includes cancer such as hepatocellular carcinoma (HCC), melanoma,
CC lung squamous cell carcinoma, ovarian carcinoma, yolk sac tumor,
CC choriocarcinoma, neuroblastoma, hepatoblastoma, Wilms' tumor, testicular
CC nonseminomatous germ cell tumor, gastric carcinoma, and liposarcoma. The
CC present sequence represents a CD28 transmembrane/intracellular signaling
CC domain fusion protein (CSR1), which can be useful for preparing the
CC composition of the invention.
XX
SQ Sequence 110 AA;
Query Match 100.0%; Score 374; Length 110;
Best Local Similarity 100.0%;
Matches 69; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLV 60
Qy 61 TVAFIIFWV 69
|||||||||
Db 61 TVAFIIFWV 69
In this case, the Office does not have the facilities for examining and comparing Applicant's sequences and the sequences of Short for in order to establish that the sequences of Morgan et al are the same as those instantly claimed. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the sequences to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989) and MPEP 2112.01.
Therefore, the prior art is deemed to anticipate the instant claims absent a showing otherwise.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 152, 154-158, 160-161, 163, 171-173, 175-176 and 179 are rejected under 35 U.S.C. 103 as being unpatentable over Morgan et al (WO 2016/094304 A1) as evidenced by Wang et al (WO 2016/149254 A1, of record) and Zhang et al (WO 2018/200586 A1, of record) and Xiao et al (Clinical Cytometry, 94B:434-443, 2018).
With respect to claim 152, Morgan et al disclose compositions comprising one or more chimeric polypeptides (chimeric antigen receptors, CARs) comprising, in an order from N-terminal to C terminal: an antigen binding domain, a hinge domain and a transmembrane domain, and a cytoplasmic signaling domain, wherein the hinge domain is a CD28 hinge domain and, wherein the cytoplasmic signaling domain comprises a CD2 signaling domain and a CD3ζ activating domain (see pages 2-4, 26, 28 and 66, claims and Figures). With respect to claim 155, the cytoplasmic signaling domain can further comprise a CD27 co-stimulatory domain (see page 28). With respect to claims 156-158, 160 and 163, the antigen binding domain can be an scFv and can be specific for the tumor associated antigen of BCMA or CD19, while the transmembrane domain can be a CD28 transmembrane domain. (see pages 2-4, 10). With respect to claims 171-173, Morgan et al disclose polynucleotides encoding the chimeric polypeptides and the polynucleotide and chimeric polypeptide in T cells or autologous T cells (see pages 38, 69 and 75). With respect to claims 175-176, Morgan et al disclose treating cancer (a hyperproliferative disorder) by administering such cells (see page 4 and claim 35). While Morgan et al is silent with respect to CD58 expression, claim 176 does not require detecting CD58 expression or selecting such a patient and the cancers of Morgan et al necessarily include hyperproliferative disorders having the properties of claim 176.
Then with respect to claim 154, while Morgan et al is silent about the sequence of CD2, as evidenced by Wang et al (see alignment below), the CD2 intracellular sequence is 100% identical to instant SEQ ID NO:8, so the CD2 intracellular domain of Morgan et al is the same as that of instant claim 154.
RESULT 1
BDE76810
(NOTE: this sequence has 60 duplicates in the database searched.
See complete list at the end of this report)
ID BDE76810 standard; protein; 116 AA.
XX
AC BDE76810;
XX
DT 03-NOV-2016 (first entry)
XX
DE CAR preparing CD2 protein fragment (residues 236-351), SEQ ID 28.
XX
KW CD2 protein; Lymphocyte function antigen-3 receptor; antimicrobial-gen.;
KW bacterial infection; cancer; cytostatic; fungal infection;
KW gene regulation; infectious disease; protozoal infection; therapeutic;
KW viral infection.
XX
OS Unidentified.
XX
CC PN WO2016149254-A1.
XX
CC PD 22-SEP-2016.
XX
CC PF 15-MAR-2016; 2016WO-US022442.
XX
PR 17-MAR-2015; 2015US-0134143P.
PR 24-APR-2015; 2015US-0152727P.
PR 23-JUN-2015; 2015US-0183595P.
PR 08-JAN-2016; 2016US-0276449P.
XX
CC PA (CHIM-) CHIMERA BIOENGINEERING INC.
XX
CC PI Wang B, Zeiner G;
XX
DR WPI; 2016-59574R/68.
DR REFSEQ; NP_001758.2.
XX
CC PT New nucleic acid comprising a polynucleotide encoding a Chimeric Antigen
CC PT Receptor (CAR), useful for making a eukaryotic cell used for treating
CC PT cancer or an infectious disease.
XX
CC PS Disclosure; SEQ ID NO 28; 108pp; English.
XX
CC The present invention relates to a novel nucleic acid comprising a
CC polynucleotide operably linked to a polynucleotide encoding a chimeric
CC antigen receptor (CAR). The CAR comprises an extracellular element, a
CC transmembrane element, and an intracellular element, wherein the
CC transmembrane element is between the extracellular element and the
CC intracellular element. The invention further claims: (1) an eukaryotic
CC cell comprising the nucleic acid; (2) a method for treating cancer or a
CC disease caused by a pathogens (including a virus, a bacteria, a
CC protozoan, or a fungus) in a subject; (3) a method for controlling
CC proliferation of a T-lymphocyte; (4) a method for controlling the
CC expression of a CAR in an eukaryotic cell; (5) a method for controlling
CC an activation of a T-lymphocyte; and (6) a method for improving a RNA
CC control device by providing a virus. The eukaryotic cell is useful for
CC treating cancer or an infectious disease. The present sequence is a CD2
CC peptide used as an intracellular element for preparing the CAR.
XX
SQ Sequence 116 AA;
Query Match 100.0%; Score 644; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 KRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSH 60
Qy 61 RPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN 116
Then with respect to claim 161, while Morgan et al is silent about the sequence of CD28 transmembrane domain, as evidenced by Zhang et al (see alignment below), the CD28 transmembrane sequence is 100% identical to instant SEQ ID NO:6, so the CD28 transmembrane domain of Morgan et al is the same as that of instant claim 161.
RESULT 2
BFT70250
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BFT70250 standard; protein; 110 AA.
XX
AC BFT70250;
XX
DT 27-DEC-2018 (first entry)
XX
DE CD28 transmembrane/intracellular signaling domain fusion protein SEQ 530.
XX
KW CD28 protein; T cell surface glycoprotein CD28; antibody production;
KW antibody therapy; cancer; choriocarcinoma; cytostatic; diagnostic test;
KW fusion protein; hepatoblastoma; hepatocellular carcinoma;
KW immuno-diagnosis; immunotherapy; liposarcoma; lung tumor; melanoma;
KW nephroblastoma; neuroblastoma; ovary tumor; protein detection;
KW recombinant protein; squamous cell carcinoma; stomach tumor;
KW testis tumor; therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2018200586-A1.
XX
CC PD 01-NOV-2018.
XX
CC PF 24-APR-2018; 2018WO-US029221.
XX
PR 26-APR-2017; 2017US-0490586P.
XX
CC PA (EURE-) EUREKA THERAPEUTICS INC.
XX
CC PI Zhang P, Xu Y, Morales J, Nakano Y, Liu H, Xiang J, Acker T;
XX
DR WPI; 2018-85622A/76.
XX
CC PT New isolated anti-glypican 3 (GPC3) construct comprises an antibody
CC PT moiety specifically recognizing a cell surface-bound GPC3, for treating
CC PT and diagnosing individual having GPC3-positive disease, e.g. melanoma or
CC PT neuroblastoma.
XX
CC PS Example 8; SEQ ID NO 530; 425pp; English.
XX
CC The present invention relates to a novel isolated anti-glypican 3 (GPC3)
CC construct (chimeric antigen receptor (CAR)) comprising an antibody moiety
CC specifically recognizing a cell surface-bound GPC3, useful for treating
CC and diagnosing individual having GPC3-positive disease. The invention
CC also provides: an isolated nucleic acid encoding the polypeptide
CC components of the isolated anti-GPC3 construct; a vector comprising the
CC isolated nucleic acid; an effector cell expressing the isolated anti-GPC3
CC construct; a kit comprising the isolated anti-GPC3 construct, the
CC isolated nucleic acid, the vector, the isolated host cell, the effector
CC cell, or the pharmaceutical composition; a method for detecting GPC3 in a
CC sample; a method for treating an individual having GPC3-positive disease;
CC a method for diagnosing an individual having GPC3-positive disease; and a
CC method for producing an isolated anti-GPC3 construct. The GPC3-positive
CC disease includes cancer such as hepatocellular carcinoma (HCC), melanoma,
CC lung squamous cell carcinoma, ovarian carcinoma, yolk sac tumor,
CC choriocarcinoma, neuroblastoma, hepatoblastoma, Wilms' tumor, testicular
CC nonseminomatous germ cell tumor, gastric carcinoma, and liposarcoma. The
CC present sequence represents a CD28 transmembrane/intracellular signaling
CC domain fusion protein (CSR1), which can be useful for preparing the
CC composition of the invention.
XX
SQ Sequence 110 AA;
Query Match 100.0%; Score 374; Length 110;
Best Local Similarity 100.0%;
Matches 69; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLV 60
Qy 61 TVAFIIFWV 69
|||||||||
Db 61 TVAFIIFWV 69
Morgan et al do not disclose the subject matter of claim 179.
Xiao et al teach characterizing a patients hyperproliferative disorder (B-ALL) for CD58 and other markers prior to CAR-T cell administration (to immunophenotype the disorder and to allow one to distinguish immature B-cells from B-ALL MRD and prevent misdiagnosis) and identifying the subject as having a hyperproliferative disorder negative for CD58 (see page 436 and abstract).
Accordingly, it would have been prima facie obvious to an artisan of ordinary skill in the art to add to the method of treatment of a subject, prior to the administering, a step of identifying the subject as having the hyperproliferative disorder characterized by proliferation of a target cell that lacks expression of CD58 because immunophenotyping a patients B-ALL for markers including CD58 before treatment has the advantage of allowing one to distinguish immature B-cells from B-ALL MRD and prevent misdiagnosis. In this case, such a step suggested by the prior art carried out before treatment identifies a subject as having a B-ALL lacks expression of CD58 as required by claim 179 so that adding such a step to the method of claim 176 would not be considered inventive.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 152, 154-165, 167-173, 175-176 179 and 181-182 are rejected under 35 U.S.C. 103 as being unpatentable over Morgan et al (WO 2016/094304 A1), Short, Jay (WO 2016/033331 A1, of record), Wang et al (WO 2016/149254 A1, of record), Zhang et al (WO 2018/200586 A1, of record), Bradner et al (WO 2017/024318 A1) and Orentas (WO 2014/065961 A1, of record).
It is first noted that in claims 159, 162 and 170, that SEQ ID NO: 1 is an amino acid sequence for a CD19 scFv, SEQ ID NO:2 is an amino acid sequence for a CD22 scFv and SEQ ID NO:20 combines SEQ ID NO:1 (an amino acid sequence for a CD19 scFv), SEQ ID NO:6 (an amino acid sequence for CD28 transmembrane domain) and SEQ ID NO:8 (an amino acid sequence for CD2 intracellular signaling domain).
With respect to claim 152, Morgan et al disclose compositions comprising one or more chimeric polypeptides (chimeric antigen receptors, CARs) comprising, in an order from N-terminal to C terminal: an antigen binding domain, a hinge domain and a transmembrane domain, and a cytoplasmic signaling domain, wherein the hinge domain is a CD28 hinge domain and, wherein the cytoplasmic signaling domain comprises a CD2 signaling domain and a CD3ζ activating domain (see pages 2-4, 26, 28 and 66, claims and Figures). With respect to claim 155, the cytoplasmic signaling domain can further comprise a CD27 co-stimulatory domain (see page 28). With respect to claims 156-158, 160 and 163, the antigen binding domain can be an scFv and can be specific for the tumor associated antigen of BCMA or CD19, while the transmembrane domain can be a CD28 transmembrane domain. (see pages 2-4, 10). With respect to claims 171-173, Morgan et al disclose polynucleotides encoding the chimeric polypeptides and the polynucleotide and chimeric polypeptide in T cells or autologous T cells (see pages 38, 69 and 75). With respect to claims 175-176, Morgan et al disclose treating cancer (a hyperproliferative disorder) by administering such cells (see page 4 and claim 35). While Morgan et al is silent with respect to CD58 expression, claim 176 does not require detecting CD58 expression or selecting such a patient and the cancers of Morgan et al necessarily include hyperproliferative disorders having the properties of claim 176.
Then with respect to claim 154, while Morgan et al is silent about the sequence of CD2, as evidenced by Wang et al (see alignment below), the CD2 intracellular sequence is 100% identical to instant SEQ ID NO:8, so the CD2 intracellular domain of Morgan et al is the same as that of instant claim 154.
RESULT 1
BDE76810
(NOTE: this sequence has 60 duplicates in the database searched.
See complete list at the end of this report)
ID BDE76810 standard; protein; 116 AA.
XX
AC BDE76810;
XX
DT 03-NOV-2016 (first entry)
XX
DE CAR preparing CD2 protein fragment (residues 236-351), SEQ ID 28.
XX
KW CD2 protein; Lymphocyte function antigen-3 receptor; antimicrobial-gen.;
KW bacterial infection; cancer; cytostatic; fungal infection;
KW gene regulation; infectious disease; protozoal infection; therapeutic;
KW viral infection.
XX
OS Unidentified.
XX
CC PN WO2016149254-A1.
XX
CC PD 22-SEP-2016.
XX
CC PF 15-MAR-2016; 2016WO-US022442.
XX
PR 17-MAR-2015; 2015US-0134143P.
PR 24-APR-2015; 2015US-0152727P.
PR 23-JUN-2015; 2015US-0183595P.
PR 08-JAN-2016; 2016US-0276449P.
XX
CC PA (CHIM-) CHIMERA BIOENGINEERING INC.
XX
CC PI Wang B, Zeiner G;
XX
DR WPI; 2016-59574R/68.
DR REFSEQ; NP_001758.2.
XX
CC PT New nucleic acid comprising a polynucleotide encoding a Chimeric Antigen
CC PT Receptor (CAR), useful for making a eukaryotic cell used for treating
CC PT cancer or an infectious disease.
XX
CC PS Disclosure; SEQ ID NO 28; 108pp; English.
XX
CC The present invention relates to a novel nucleic acid comprising a
CC polynucleotide operably linked to a polynucleotide encoding a chimeric
CC antigen receptor (CAR). The CAR comprises an extracellular element, a
CC transmembrane element, and an intracellular element, wherein the
CC transmembrane element is between the extracellular element and the
CC intracellular element. The invention further claims: (1) an eukaryotic
CC cell comprising the nucleic acid; (2) a method for treating cancer or a
CC disease caused by a pathogens (including a virus, a bacteria, a
CC protozoan, or a fungus) in a subject; (3) a method for controlling
CC proliferation of a T-lymphocyte; (4) a method for controlling the
CC expression of a CAR in an eukaryotic cell; (5) a method for controlling
CC an activation of a T-lymphocyte; and (6) a method for improving a RNA
CC control device by providing a virus. The eukaryotic cell is useful for
CC treating cancer or an infectious disease. The present sequence is a CD2
CC peptide used as an intracellular element for preparing the CAR.
XX
SQ Sequence 116 AA;
Query Match 100.0%; Score 644; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 KRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSH 60
Qy 61 RPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN 116
Then with respect to claim 161, while Morgan et al is silent about the sequence of CD28 transmembrane domain, as evidenced by Zhang et al (see alignment below), the CD28 transmembrane sequence is 100% identical to instant SEQ ID NO:6, so the CD28 transmembrane domain of Morgan et al is the same as that of instant claim 161.
RESULT 2
BFT70250
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BFT70250 standard; protein; 110 AA.
XX
AC BFT70250;
XX
DT 27-DEC-2018 (first entry)
XX
DE CD28 transmembrane/intracellular signaling domain fusion protein SEQ 530.
XX
KW CD28 protein; T cell surface glycoprotein CD28; antibody production;
KW antibody therapy; cancer; choriocarcinoma; cytostatic; diagnostic test;
KW fusion protein; hepatoblastoma; hepatocellular carcinoma;
KW immuno-diagnosis; immunotherapy; liposarcoma; lung tumor; melanoma;
KW nephroblastoma; neuroblastoma; ovary tumor; protein detection;
KW recombinant protein; squamous cell carcinoma; stomach tumor;
KW testis tumor; therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2018200586-A1.
XX
CC PD 01-NOV-2018.
XX
CC PF 24-APR-2018; 2018WO-US029221.
XX
PR 26-APR-2017; 2017US-0490586P.
XX
CC PA (EURE-) EUREKA THERAPEUTICS INC.
XX
CC PI Zhang P, Xu Y, Morales J, Nakano Y, Liu H, Xiang J, Acker T;
XX
DR WPI; 2018-85622A/76.
XX
CC PT New isolated anti-glypican 3 (GPC3) construct comprises an antibody
CC PT moiety specifically recognizing a cell surface-bound GPC3, for treating
CC PT and diagnosing individual having GPC3-positive disease, e.g. melanoma or
CC PT neuroblastoma.
XX
CC PS Example 8; SEQ ID NO 530; 425pp; English.
XX
CC The present invention relates to a novel isolated anti-glypican 3 (GPC3)
CC construct (chimeric antigen receptor (CAR)) comprising an antibody moiety
CC specifically recognizing a cell surface-bound GPC3, useful for treating
CC and diagnosing individual having GPC3-positive disease. The invention
CC also provides: an isolated nucleic acid encoding the polypeptide
CC components of the isolated anti-GPC3 construct; a vector comprising the
CC isolated nucleic acid; an effector cell expressing the isolated anti-GPC3
CC construct; a kit comprising the isolated anti-GPC3 construct, the
CC isolated nucleic acid, the vector, the isolated host cell, the effector
CC cell, or the pharmaceutical composition; a method for detecting GPC3 in a
CC sample; a method for treating an individual having GPC3-positive disease;
CC a method for diagnosing an individual having GPC3-positive disease; and a
CC method for producing an isolated anti-GPC3 construct. The GPC3-positive
CC disease includes cancer such as hepatocellular carcinoma (HCC), melanoma,
CC lung squamous cell carcinoma, ovarian carcinoma, yolk sac tumor,
CC choriocarcinoma, neuroblastoma, hepatoblastoma, Wilms' tumor, testicular
CC nonseminomatous germ cell tumor, gastric carcinoma, and liposarcoma. The
CC present sequence represents a CD28 transmembrane/intracellular signaling
CC domain fusion protein (CSR1), which can be useful for preparing the
CC composition of the invention.
XX
SQ Sequence 110 AA;
Query Match 100.0%; Score 374; Length 110;
Best Local Similarity 100.0%;
Matches 69; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLV 60
Qy 61 TVAFIIFWV 69
|||||||||
Db 61 TVAFIIFWV 69
Morgan et al do not disclose the subject matter of the other claims.
Short teach chimeric polypeptides (chimeric antigen receptors, CARs) comprising, in an order from N-terminal to C terminal: an antigen binding domain and a transmembrane domain, a cytoplasmic signaling domain, wherein the cytoplasmic signaling domain comprises a CD137(4-1BB) signaling domain (lacks CD2 signaling domain) and a cd3-zeta activating domain and compositions thereof, wherein the antigen binding domain can be an scFv and can be specific for tumor antigens CD19, CD20 or CD22, which are encompassed by the chimeric polypeptides or transgenic T cell receptors of claims 164 and 165 (see pages 30-35, 77 and 81 and claims). With respect to claims 167-169 and 179, the composition can comprise an additional CAR comprising a CD3 zeta domain and which comprises an antigen binding domain that binds CD19, CD20 or CD22 such that the CAR is specific for CD22 and the chimeric polypeptide is specific for CD19 or the CAR is specific for CD19 and the chimeric polypeptide is specific for CD20 (see pages 27, 31-34 and 81-84 and claims 1-26). With respect to claim 181, Short teach polynucleotides encoding the transgenic chimeric polypeptides and the polynucleotide and chimeric polypeptides in T cells (see pages 10, 24-29 and 79).
With respect to claims 175-176 and 181, Short teach treating cancer (a hyperproliferative disorder) by administer such cells (see page 4 and claim 35). While Short is silent with respect to CD58 expression, claims 176 and 181 do not require detecting CD58 expression or selecting such a patient and the cancers of Short necessarily include hyperproliferative disorders having the properties of claims 176 and 181.
With respect to claims 159, 162 and 170, while neither Morgan et al or Short identifies a CD19 scFv sequence for use in a CAR, Bradner et al teach a CD19 scFv antigen binding domain sequence that is 100% identical to instant SEQ ID NO: 1 and comprised in SEQ ID NO:20 for use in chimeric antigen receptors that target CD19 ( see alignment below, figures and claims).
RESULT 1
BDN98284
(NOTE: this sequence has 42 duplicates in the database searched.
See complete list at the end of this report)
ID BDN98284 standard; protein; 267 AA.
XX
AC BDN98284;
XX
DT 06-APR-2017 (first entry)
XX
DE CD19 scFv extracellular targeting ligand domain, SEQ ID 10.
XX
KW B-lymphocyte antigen CD19; immune inhibition; immune stimulation;
KW single chain antibody.
XX
OS Unidentified.
XX
CC PN WO2017024318-A1.
XX
CC PD 09-FEB-2017.
XX
CC PF 08-AUG-2016; 2016WO-US046088.
XX
PR 06-AUG-2015; 2015US-0202076P.
PR 15-APR-2016; 2016US-0323575P.
PR 15-APR-2016; 2016US-0323591P.
XX
CC PA (DAND ) DANA FARBER CANCER INST INC.
XX
CC PI Bradner J, Roberts J, Nabet B, Winter G, Phillips AJ;
CC PI Heffernan TP, Buckley D;
XX
DR WPI; 2017-10818A/18.
XX
CC PT New immune effector cell comprises chimeric antigen receptor polypeptide,
CC PT useful for reducing adverse immune response in subject caused by
CC PT activated immune effector cell that expresses chimeric antigen receptor
CC PT polypeptide.
XX
CC PS Example 1; SEQ ID NO 10; 456pp; English.
XX
CC The present invention relates to a novel immune effector cell useful for
CC reducing adverse immune response in a subject. The immune effector cell
CC comprises chimeric antigen receptor (CAR) polypeptide. The invention
CC further provides a method for reducing the adverse immune response caused
CC by an activated immune effector cell that expresses CAR polypeptide. The
CC present sequence represents a CD19 scFv extracellular targeting ligand
CC domain, which is used in the invention for reducing adverse immune
CC response in a subject.
XX
SQ Sequence 267 AA;
Query Match 100.0%; Score 1400; Length 267;
Best Local Similarity 100.0%;
Matches 267; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQ 60
Qy 61 KPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTF 120
Qy 121 GGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYG 180
Qy 181 VSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIY 240
Qy 241 YCAKHYYYGGSYAMDYWGQGTSVTVSS 267
|||||||||||||||||||||||||||
Db 241 YCAKHYYYGGSYAMDYWGQGTSVTVSS 267
With respect to claims 159 and 162, while neither Morgan et al or Short identifies a CD22 scFv sequence for use in a CAR, Orentas et al teach a CD22 scFv antigen binding domain sequence that is 100% identical to instant SEQ ID NO: 2 for use in chimeric antigen receptors that target CD22 (see alignment below, page 4, figures and claims).
RESULT 7
BBF65866
(NOTE: this sequence has 7 duplicates in the database searched.
See complete list at the end of this report)
ID BBF65866 standard; protein; 480 AA.
XX
AC BBF65866;
XX
DT 19-JUN-2014 (first entry)
XX
DE Human CAR second generation version 1, SEQ ID 23.
XX
KW CD28 antigen; CD3 zeta; CD8 antigen; GM-CSF;
KW T cell surface glycoprotein CD28; T-cell surface glycoprotein CD8;
KW antibody therapy; cancer; cytostatic; diagnostic test;
KW granulocyte colony-stimulating factor; immuno-diagnosis;
KW prophylactic to disease; therapeutic.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Region 1..22
FT /note= "Granulocyte colony-stimulating factor leader
FT sequence"
XX
CC PN WO2014065961-A1.
XX
CC PD 01-MAY-2014.
XX
CC PF 18-SEP-2013; 2013WO-US060332.
XX
PR 24-OCT-2012; 2012US-0717960P.
XX
CC PA (USSH ) US DEPT HEALTH & HUMAN SERVICES.
XX
CC PI Dimitrov DS, Mackall CL, Orentas RJ, Pastan IH;
XX
DR WPI; 2014-H87417/34.
XX
CC PT New chimeric antigen receptor (CAR) useful in pharmaceutical composition
CC PT is useful for treating cancer, comprising antigen binding domain
CC PT comprising amino acid sequence, transmembrane domain, and intracellular T
CC PT cell signaling domain.
XX
CC PS Claim 13; SEQ ID NO 23; 52pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC useful in pharmaceutical composition for treating and preventing cancer.
CC The CAR comprises an antigen binding domain corresponding to SEQ ID NO's:
CC 1-6 (see BBF65844-BBF65849), a transmembrane domain and an intracellular
CC T cell signaling domain. The invention further relates to: (a) a nucleic
CC acid comprising nucleotide sequence encoding the CAR; (b) a recombinant
CC expression vector; (c) an isolated host cell comprising the recombinant
CC expression vector; (d) a population of cells comprising at least one host
CC cell; (e) an antibody or its antigen binding portion thereof specifically
CC binds to the CAR; (f) a pharmaceutical composition; and (g) a method of
CC detecting the presence of cancer in a mammal. The present sequence
CC represents a CAR second generation version 1 comprising human granulocyte
CC colony-stimulating factor (GM-CSF) leader sequence, antigen binding
CC domain (m971), CD8 transmembrane domain, CD28 and CD3 zeta intracellular
CC T cell signaling domains and used in the invention for treating and
CC preventing cancer.
XX
SQ Sequence 480 AA;
Query Match 100.0%; Score 1346; Length 480;
Best Local Similarity 100.0%;
Matches 258; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNW 60
Qy 61 IRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYY 120
Qy 121 CAREVTGDLEDAFDIWGQGTMVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CAREVTGDLEDAFDIWGQGTMVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTI 180
Qy 181 WSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 WSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQ 240
Qy 241 QSYSIPQTFGQGTKLEIK 258
||||||||||||||||||
Db 241 QSYSIPQTFGQGTKLEIK 258
Accordingly, it would have been prima facie obvious to an artisan of ordinary skill in the art to make compositions comprising chimeric polypeptides comprising, in an order from N-terminal to C terminal: an antigen binding domain, a CD28 hinge domain and a transmembrane domain, a cytoplasmic signaling domain, wherein the cytoplasmic signaling domain comprises a CD2 signaling domain and a CD3-zeta activating domain, with an antigen binding domain that binds to BCMA, CD19, CD20 or CD22 and such a CAR in compositions comprising two or more chimeric antigen receptors wherein the other CAR comprises an antigen binding domain, a cytoplasmic signaling domain comprising a CD137(4-1BB) signaling domain and a cd3-zeta activating domain and compositions thereof wherein the antigen binding domain of one CAR comprises a scFv specific for CD22, and wherein the scFv specific for CD22 comprises an amino acid sequence with at least 80% identity to a sequence of SEQ ID NO: 2; and/or wherein the antigen binding domain of one CAR comprises a scFv specific for CD19, and wherein the scFv specific for CD19 comprises an amino acid sequence with at least 80% identity to a sequence of SEQ ID NO: 1 and compositions wherein the chimeric polypeptide comprises an amino acid sequence with at least 80% identity to any one of the sequences of SEQ ID NOs: 20 along with such compositions that additionally comprise a CD22 CAR, a CD20 CAR or CD19 CAR as encompassed by the claims and as disclosed or suggested by Morgan et al and/or Short because such compositions would have the advantage of using known sequences and CAR domains to create compositions that target two or more known B cell tumor antigens which would allow streamlined and faster genetic engineering steps along with the advantage of targeting multiple B cell tumor antigens to more effectively treat the B cell tumor. Additionally, using different CARs with different signaling domains (one CAR with a CD2 signaling domain and one CAR with a CD137(4-1BB) domain) would have the advantage of activating T cells by different mechanisms such that the CAR T cell therapy would be more effective.
Notably, using art known sequences and domains in the CAR constructs would be seen as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Finally, as methods of making chimeric antigen receptors using such sequences and domains were known in the art and methods of treating patients with such CAR T cell compositions comprising multiple CARs were known in the art, one of skill in the art would have had a reasonable expectation of success in making such compositions comprising chimeric antigen receptors as instantly claimed and a reasonable expectation of success in using them to treat patients with cancer.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner can normally be reached on Monday through Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
January 27, 2026