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 .
Status of the Claims
Claims 1 – 2, 4 – 5, 14, 18 – 19, 26 – 30, 32 – 35, 39 – 43 were pending, with non-elected claims 33 – 35 and 39 – 40 withdrawn from consideration. No claim has been amended, canceled, or added. Claims 1 – 2, 4 – 5, 14, 18 – 19, 26 – 30, 32, and 41 – 43 are the subject of this Office Action.
REJECTIONS WITHDRAWN
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 29 – 30 were rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism.
After further consideration, this rejection is withdrawn.
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.
Claims 1 – 2, 4 – 5, 14, 18 – 19, 26 – 30, 32, and 41 – 43 were 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.
After further consideration, this rejection is withdrawn.
REJECTIONS MAINTAINED
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.
Claims 1 – 2, 4 – 5, 14, 18 – 19, 26, 28 – 30, 32, and 41 – 43 are rejected under 35 U.S.C. 103 as being unpatentable over MAUS (WO 2018/132506 A1, published 07/19/2018; see PTO-892: Notice of References Cited of 07/11/2025) in view of BROGDON (US 2014/271635 A1, published 09/18/2014; see PTO-892 of 07/11/2025).
The present application is directed to a chimeric antigen receptor (CAR) comprising (i) an extracellular domain comprising a CD37-binding domain comprising: a variable heavy (VH) domain comprising a complementarity determining region 1 (CDR1), CDR2, and CDR3 of SEQ ID NO: 1 and a variable light (VL) domain comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 2; and a CD19-binding domain comprising a VH domain comprising a complementarity determining region 1 (CDR1), CDR2, and CDR3 of SEQ ID NO: 12 and a VL domain comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 13; (ii) a transmembrane domain; and (iii) an intracellular signaling domain.
MAUS is directed to a chimeric antigen receptor (CAR) polypeptide comprising:
a) an extracellular domain comprising a target-binding sequence; b) a transmembrane domain; c) a co-stimulatory domain; and d) a T cell intracellular signaling domain that lacks a functional ITAM3 sequence. See claim 1. MAUS discloses a CD37-CAR and a CD19-CAR, which exhibit in vitro tumor killing, and that the CAR can be a bispecific CAR that is specific to two different antigens. See paragraphs 00119, 00157, and 00187. MAUS teaches that a CAR' s extracellular target binding domain comprises or consists essentially of a single-chain Fv (scFv) fragment created by fusing the VH and VL domains of an antibody. See paragraph 00154.
Furthermore, MAUS discloses a CAR targeting CD37 and having the sequences (which should thus include the CDRs) of present SEQ ID NOs: 1 and 2 of present claims 1, 2, and 42. Multiple sequences disclosed by MAUS teach present SEQ ID NOs: 1 and 2 with 100% identity. For example, MAUS’ SEQ ID NO: 6 and 12 each is identical to present SEQ ID NO: 1 of present claims 1, 2, and 42, and MAUS’ SEQ ID NO: 8 and 10 each is identical to present SEQ ID NO: 2 of present claims 1, 2, and 42. See Appendix.
Thus, MAUS renders a CAR comprising (i) an extracellular domain comprising a CD37-binding domain comprising: a variable heavy (VH) domain comprising a complementarity determining region 1 (CDR1), CDR2, and CDR3 of SEQ ID NO: 1 and a variable light (VL) domain comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 2; and a CD19-binding domain obvious. However, MAUS does not expressly disclose a CD19-binding domain having the sequences of SEQ ID NOs: 12 and 13.
BROGDON is directed to CARs specific to CD19, vectors encoding the same, and recombinant T cells comprising the CD19 CAR. See abstract. BROGDON discloses the sequences (which should include the CDRs) of SEQ ID NOs: 12 and 13 of present claims 1, 2, and 43. Multiple sequences disclosed by BROGDON teach present SEQ ID NOs: 12 and 13 with 100% identity. For example, BROGDON’s SEQ ID NO: 116 is identical to present SEQ ID NO: 12 of present claims 1, 2, and 43, and BROGDON’s SEQ ID NO: 117 is identical to present SEQ ID NO: 13 of present claims 1, 2, and 43. See Appendix.
Because MAUS discloses a CAR targeting CD37 (and the sequences thereof) and a CAR targeting CD19 that are effective at killing tumors and teaches that CARs may have two binding domains and BROGDON teaches a CAR with a CD-19 binding domain, it would have been obvious to one having ordinary skill in the art to modify MAUS’ CAR to include BROGDON’s CD-19-binding domain. There would have been a reasonable expectation of success given that CD37 and CD19, as well as the sequences targeting them, has been known to successfully treat cancer as evidenced by the applied prior art.
Thus, MAUS in view of BROGDON renders the CAR of claims 1, 2, 42, and 43 obvious.
Regarding claims 4 and 5, because each binding domain only has one N- terminal end and one C-terminal end, the positioning of one binding domain in relation to the other consists of a small, finite number of possibilities. Thus, although neither MAUS nor BROGDON expressly discloses that the CD19-binding domain is positioned N- terminal to the CD37-binding domain of claim 4 or that the CD37-binding domain is positioned N- terminal to the CD 19-binding domain of claim 5, MAUS’ bispecific CAR renders the claimed positionings obvious.
Regarding claim 14, BROGDON discloses the sequence of SEQ ID NO: 20. BROGDON’s SEQ ID NO: 6 discloses present SEQ ID NO: 20 with 100% identity. See Appendix.
Regarding claim 18 and 19, MAUS discloses that the orientation of a humanized murine antibody-derived single-chain variable fragment can be VL- VH or VH-VL. See paragraph 00161.
Regarding claim 26, MAUS discloses a nucleic acid encoding any of the CAR polypeptides. See claim 24.
Regarding claim 28, BROGDON discloses an expression vector with a signal sequence. See paragraph 0362.
Regarding claims 29 and 30, MAUS discloses a T cell comprising the CAR polypeptide or a nucleic acid encoding any of the CAR polypeptides. See claims 24 and 25.
Regarding claim 32, MAUS discloses that the disclosed composition further comprises a pharmaceutically acceptable carrier. See claims 41 and 42.
Regarding claim 41, BROGDON discloses the sequence of SEQ ID NO: 20. BROGDON’s SEQ ID NO: 6 is identical to SEQ ID NO: 20. See Appendix.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over MAUS in view of BROGDON as applied to claims 1 – 2, 4 – 5, 14, 18 – 19, 26, 28 – 30, 32, and 41 – 43 above, and further in view of GARGETT (Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014 Oct 28;5:235; see PTO-892 of 02/09/2024).
The teachings of MAUS and BROGDON with regard to claims 1 – 2, 4 – 5, 14, 18 – 19, 26, 28 – 30, 32, and 41 – 43 are discussed above and fully incorporated here.
Although MAUS and BROGDON render a CAR comprising an extracellular domain comprising a CD37-binding domain and a CD19-binding domain of independent claim 1 obvious as discussed above, neither reference expressly discloses the suicide gene of present claim 27. Nonetheless GARGETT renders this limitation obvious.
GARGETT is directed to CAR T cells engineered to co-express an inducible caspase 9 “suicide gene” as a “safety switch” to permit the elimination of inappropriately activated CAR T cells following their administration to cancer patients to limit undesired on-target, off-tumor toxicity; see entire document (e.g., the abstract).
It would have been prima facie obvious to one ordinarily skilled in the art as of the effective filing date of the claimed invention to have produced the claimed invention as suggested by the teachings of GARGETT by producing a nucleic acid molecule encoding the CAR and an inducible caspase 9 “suicide gene”. One ordinarily skilled in the art as of the effective filing date of the claimed invention would have been motivated to do so in order to treat the cancer in the subject, while permitting the elimination of inappropriately activated CAR T cells following their administration to the subject to limit undesired on-target, off-tumor toxicity.
Response to Arguments
On p. 8 under “Rejections Under 35 U.S.C § 103”, second paragraph, of the reply of 12/11/2025, Applicant argues “[t]he Maus reference was published on July 19, 2018. The Office has assigned the effective filing date of the instant application as June 21, 2019, which is within one year of the publication date of Maus. The sole inventor of the instant application, Marcela Maus, is also the first-named inventor of the Maus reference. Additionally, the subject matter in the Maus reference leveraged by the Office to support the rejection under 35 U.S.C. § 103 of the instant claims is an anti-CD37/anti- CD19 bispecific CAR, as claimed in the instant application, for which inventor Maus is the sole inventor. Accordingly, AIA § 102(b)(1) provides that the disclosure of Maus is not prior art under AIA § 102(a)(1) because the instant application enjoys the one-year grace period prior art exception.”
However, although the MAUS reference does name Marcela V. Maus as an inventor in the reference, it also names Mark Cobbold and Irene Scarfo as co-inventors. Thus the MAUS reference has a different inventive entity than the present application, which names Marcela V. Maus as a sole inventor, and the exceptions under 35 U.S.C § 102(b) does not apply in this instant case. “The inventive entity is different if not all inventors are the same. The fact that the application and reference have one or more inventors in common is immaterial. Ex parte DesOrmeaux, 25 USPQ2d 2040 (Bd. Pat. App. & Inter. 1992).” See 2136.04.
Furthermore, the MAUS reference has a filing date of 01/10/2018, which is more than one year prior to the effective filing date of 06/21/2019 of the present application. Thus, the MAUS reference may be applied as prior art under 35 U.S.C. 102(a)(2).
On p. 8, last paragraph of the reply, Applicant argues that “[l]ooking at the disclosure of Brogdon, the skilled artisan would not envisage a bispecific CAR, let alone a bispecific CAR targeting CD37 in addition to CD19, as Brogdon does not disclose or suggest either a bispecific CAR or a CD37-targeting CAR. Additionally, it was known at the time of filing that T cells express CD37, which regulates their proliferation.10 A person of skill would therefore not be motivated to engineer an anti-CD37 CAR, including an anti-CD37/anti-CD19 bispecific CAR, as they would believe that the CD37-binding domain would target CD37- expressing T cells, thereby inducing fratricide.”
Applicant’s argument and cited references have been fully considered but not found persuasive because MAUS teaches that the disclosed “CAR is a bispecific CAR. A bispecific CAR is specific to two different antigens” (see ¶ 00157) and teaches that CD37 as a good target in the treatment of cancer, a plasma cell disorder, or an autoimmune disease (see claims 9, 18 – 19, 30 – 31, 36, 38, 40). Furthermore, MAUS teaches that “[i]ncreasing concentration of either CD37-CAR T or CAR T-19 led to similar levels of killing of target cells, while no killing was observed in the control group (UTD)” (see ¶ 00118 and FIG 47), and thus it would have been obvious to one having ordinary skill in the art to target both CD37 and CD19 with a bispecific CAR. BROGDON provides “an optimized and humanized antibody fragments (e.g., scFv) that bind the Cluster of Differentiation 19 protein (CD19) integrated into a Chimeric Antigen Receptor (CAR) construct that will not elicit an immune response in patients, is safe to use long term, and maintains or has better clinical effectiveness as compared to known CART therapy for treatment of B cell derived cancers”. It would have been obvious to one having ordinary skill in the art to modify MAUS’ CD37 bispecific CAR to include BROGDON’s CD19 CAR. There would have been a reasonable expectation of success considering that CD37 and CD19 have been known cancer antigens targeted by CARs and bispecific CARs have been known to be effective in the treatment of cancer, as evidenced by the applied prior art.
On p. 9, second to last paragraph, of the reply, Applicant argues that “as articulated above, the Maus reference is not available as prior art for the instant claims. With Maus, the claims are non-obvious because Brogdon and Gargett do not teach or disclose CD37-targeting CARs or bispecific CARs.
Accordingly, the Maus reference cannot serve as prior art for claim 27, which is additionally nonobvious over Brogdon and Gargett.”
However, as discussed above, the MAUS reference is valid prior art, and the rejections under MAUS in combination with BROGDON or in combination with BROGDON and GARGETT are maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
APPENDIX
Alignment with SEQ ID NO: 1
BFM31501
ID BFM31501 standard; protein; 116 AA.
XX
AC BFM31501;
XX
DT 06-SEP-2018 (first entry)
XX
DE Anti-CD37/anti-OTK3 scFv antibody VH, SEQ ID 6.
XX
KW CD37; OTK3 protien; acute myelogenous leukemia;
KW anaplastic large cell lymphoma; autoimmune disease;
KW b-cell acute lymphoblastic leukemia; b-cell lymphoma; burkitts lymphoma;
KW cancer; cutaneous t-cell lymphoma; cytostatic;
KW heavy chain variable region; hematological-gen.; immunomodulator;
KW immunosuppressive; immunotherapy; leukemia; lymphoma;
KW mantle cell lymphoma; multiple myeloma; recombinant protein;
KW single chain antibody; t-cell lymphoma; therapeutic.
XX
OS Mus sp.
XX
CC PN WO2018132506-A1.
XX
CC PD 19-JUL-2018.
XX
CC PF 10-JAN-2018; 2018WO-US013213.
XX
PR 10-JAN-2017; 2017US-0444605P.
PR 16-MAR-2017; 2017US-0472275P.
PR 01-NOV-2017; 2017US-0580243P.
PR 09-NOV-2017; 2017US-0584060P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Maus MV, Cobbold M, Scarfo I;
XX
DR WPI; 2018-56508P/51.
XX
CC PT New chimeric antigen receptor (CAR) polypeptide comprises e.g.
CC PT extracellular domain comprising a target-binding sequence, a
CC PT transmembrane domain, and co-stimulatory domain, for treating cancer,
CC PT plasma cell disorder, or autoimmune disease.
XX
CC PS Example 8; SEQ ID NO 6; 138pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC polypeptide, useful for treating cancer, plasma cell disorder, or
CC autoimmune disease. The CAR polypeptide comprises an extracellular domain
CC comprising a target-binding sequence, a transmembrane domain and a co-
CC stimulatory domain. The invention further claims: (1) a mammalian cell
CC comprising: (a) the CAR polypeptide; or (b) a nucleic acid encoding the
CC CAR polypeptide; (2) a method for treating cancer, a plasma cell
CC disorder, or an autoimmune disease in a subject; and (3) a composition
CC comprising the CAR polypeptide and a carrier. The CAR polypeptide of the
CC invention is useful for treating cancer including lymphoma such as B-cell
CC non-Hodgkin lymphoma, mantle cell lymphoma, Burkitt's lymphoma, B cell
CC lymphoblastic lymphoma or T cell lymphoma, peripheral T cell lymphoma,
CC cutaneous T-cell lymphoma or anaplastic large cell lymphoma or leukemia
CC such as acute myeloid leukemia. The present sequence is an anti-CD37/anti
CC -OTK3 single chain variable region (scFv) antibody heavy chain variable
CC region (VH), used in a CAR polypetide for treating cancer in a subject.
XX
SQ Sequence 116 AA;
ALIGNMENT:
Query Match 100.0%; Score 614; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AVQLVQSGAEVKKPGSSVKVSCKASGYSFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTTY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AVQLVQSGAEVKKPGSSVKVSCKASGYSFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTTY 60
Qy 61 NRKFKGRVTLTVDKSSSTAYMELSSLRSEDTAVYYCARSVGPMDYWGQGTLVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NRKFKGRVTLTVDKSSSTAYMELSSLRSEDTAVYYCARSVGPMDYWGQGTLVTVSS 116
BFM31507
ID BFM31507 standard; protein; 116 AA.
XX
AC BFM31507;
XX
DT 06-SEP-2018 (first entry)
XX
DE Anti-CD37/anti-OTK3 scFv antibody VH, SEQ ID 12.
XX
KW CD37; OTK3 protien; acute myelogenous leukemia;
KW anaplastic large cell lymphoma; autoimmune disease;
KW b-cell acute lymphoblastic leukemia; b-cell lymphoma; burkitts lymphoma;
KW cancer; cutaneous t-cell lymphoma; cytostatic;
KW heavy chain variable region; hematological-gen.; immunomodulator;
KW immunosuppressive; immunotherapy; leukemia; lymphoma;
KW mantle cell lymphoma; multiple myeloma; recombinant protein;
KW single chain antibody; t-cell lymphoma; therapeutic.
XX
OS Mus sp.
XX
CC PN WO2018132506-A1.
XX
CC PD 19-JUL-2018.
XX
CC PF 10-JAN-2018; 2018WO-US013213.
XX
PR 10-JAN-2017; 2017US-0444605P.
PR 16-MAR-2017; 2017US-0472275P.
PR 01-NOV-2017; 2017US-0580243P.
PR 09-NOV-2017; 2017US-0584060P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Maus MV, Cobbold M, Scarfo I;
XX
DR WPI; 2018-56508P/51.
XX
CC PT New chimeric antigen receptor (CAR) polypeptide comprises e.g.
CC PT extracellular domain comprising a target-binding sequence, a
CC PT transmembrane domain, and co-stimulatory domain, for treating cancer,
CC PT plasma cell disorder, or autoimmune disease.
XX
CC PS Example 8; SEQ ID NO 12; 138pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC polypeptide, useful for treating cancer, plasma cell disorder, or
CC autoimmune disease. The CAR polypeptide comprises an extracellular domain
CC comprising a target-binding sequence, a transmembrane domain and a co-
CC stimulatory domain. The invention further claims: (1) a mammalian cell
CC comprising: (a) the CAR polypeptide; or (b) a nucleic acid encoding the
CC CAR polypeptide; (2) a method for treating cancer, a plasma cell
CC disorder, or an autoimmune disease in a subject; and (3) a composition
CC comprising the CAR polypeptide and a carrier. The CAR polypeptide of the
CC invention is useful for treating cancer including lymphoma such as B-cell
CC non-Hodgkin lymphoma, mantle cell lymphoma, Burkitt's lymphoma, B cell
CC lymphoblastic lymphoma or T cell lymphoma, peripheral T cell lymphoma,
CC cutaneous T-cell lymphoma or anaplastic large cell lymphoma or leukemia
CC such as acute myeloid leukemia. The present sequence is an anti-CD37/anti
CC -OTK3 single chain variable region (scFv) antibody heavy chain variable
CC region (VH), used in a CAR polypetide for treating cancer in a subject.
XX
SQ Sequence 116 AA;
ALIGNMENT:
Query Match 100.0%; Score 614; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AVQLVQSGAEVKKPGSSVKVSCKASGYSFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTTY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AVQLVQSGAEVKKPGSSVKVSCKASGYSFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTTY 60
Qy 61 NRKFKGRVTLTVDKSSSTAYMELSSLRSEDTAVYYCARSVGPMDYWGQGTLVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NRKFKGRVTLTVDKSSSTAYMELSSLRSEDTAVYYCARSVGPMDYWGQGTLVTVSS 116
Alignment with SEQ ID NO: 2
RESULT 1
BFM31503
(NOTE: this sequence has 6 duplicates in the database searched.
See complete list at the end of this report)
ID BFM31503 standard; protein; 108 AA.
XX
AC BFM31503;
XX
DT 06-SEP-2018 (first entry)
XX
DE Anti-CD37/anti-OTK3 scFv antibody VL, SEQ ID 8.
XX
KW CD37; OTK3 protien; acute myelogenous leukemia;
KW anaplastic large cell lymphoma; autoimmune disease;
KW b-cell acute lymphoblastic leukemia; b-cell lymphoma; burkitts lymphoma;
KW cancer; cutaneous t-cell lymphoma; cytostatic; hematological-gen.;
KW immunomodulator; immunosuppressive; immunotherapy; leukemia;
KW light chain variable region; lymphoma; mantle cell lymphoma;
KW multiple myeloma; recombinant protein; single chain antibody;
KW t-cell lymphoma; therapeutic.
XX
OS Mus sp.
XX
CC PN WO2018132506-A1.
XX
CC PD 19-JUL-2018.
XX
CC PF 10-JAN-2018; 2018WO-US013213.
XX
PR 10-JAN-2017; 2017US-0444605P.
PR 16-MAR-2017; 2017US-0472275P.
PR 01-NOV-2017; 2017US-0580243P.
PR 09-NOV-2017; 2017US-0584060P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Maus MV, Cobbold M, Scarfo I;
XX
DR WPI; 2018-56508P/51.
XX
CC PT New chimeric antigen receptor (CAR) polypeptide comprises e.g.
CC PT extracellular domain comprising a target-binding sequence, a
CC PT transmembrane domain, and co-stimulatory domain, for treating cancer,
CC PT plasma cell disorder, or autoimmune disease.
XX
CC PS Example 8; SEQ ID NO 8; 138pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC polypeptide, useful for treating cancer, plasma cell disorder, or
CC autoimmune disease. The CAR polypeptide comprises an extracellular domain
CC comprising a target-binding sequence, a transmembrane domain and a co-
CC stimulatory domain. The invention further claims: (1) a mammalian cell
CC comprising: (a) the CAR polypeptide; or (b) a nucleic acid encoding the
CC CAR polypeptide; (2) a method for treating cancer, a plasma cell
CC disorder, or an autoimmune disease in a subject; and (3) a composition
CC comprising the CAR polypeptide and a carrier. The CAR polypeptide of the
CC invention is useful for treating cancer including lymphoma such as B-cell
CC non-Hodgkin lymphoma, mantle cell lymphoma, Burkitt's lymphoma, B cell
CC lymphoblastic lymphoma or T cell lymphoma, peripheral T cell lymphoma,
CC cutaneous T-cell lymphoma or anaplastic large cell lymphoma or leukemia
CC such as acute myeloid leukemia. The present sequence is an anti-CD37/anti
CC -OTK3 single chain variable region (scFv) antibody light chain variable
CC region (VL), used in a CAR polypetide for treating cancer in a subject.
XX
SQ Sequence 108 AA;
Query Match 100.0%; Score 567; Length 108;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRTSENVYSYLAWYQQKPGKAPKLLVSSAKTLAEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRTSENVYSYLAWYQQKPGKAPKLLVSSAKTLAEGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQHHSDNPWTFGQGTKVEIKR 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQHHSDNPWTFGQGTKVEIKR 108
BFM31505
ID BFM31505 standard; protein; 108 AA.
XX
AC BFM31505;
XX
DT 06-SEP-2018 (first entry)
XX
DE Anti-CD37/anti-OTK3 scFv antibody VL, SEQ ID 10.
XX
KW CD37; OTK3 protien; acute myelogenous leukemia;
KW anaplastic large cell lymphoma; autoimmune disease;
KW b-cell acute lymphoblastic leukemia; b-cell lymphoma; burkitts lymphoma;
KW cancer; cutaneous t-cell lymphoma; cytostatic; hematological-gen.;
KW immunomodulator; immunosuppressive; immunotherapy; leukemia;
KW light chain variable region; lymphoma; mantle cell lymphoma;
KW multiple myeloma; recombinant protein; single chain antibody;
KW t-cell lymphoma; therapeutic.
XX
OS Mus sp.
XX
CC PN WO2018132506-A1.
XX
CC PD 19-JUL-2018.
XX
CC PF 10-JAN-2018; 2018WO-US013213.
XX
PR 10-JAN-2017; 2017US-0444605P.
PR 16-MAR-2017; 2017US-0472275P.
PR 01-NOV-2017; 2017US-0580243P.
PR 09-NOV-2017; 2017US-0584060P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Maus MV, Cobbold M, Scarfo I;
XX
DR WPI; 2018-56508P/51.
XX
CC PT New chimeric antigen receptor (CAR) polypeptide comprises e.g.
CC PT extracellular domain comprising a target-binding sequence, a
CC PT transmembrane domain, and co-stimulatory domain, for treating cancer,
CC PT plasma cell disorder, or autoimmune disease.
XX
CC PS Example 8; SEQ ID NO 10; 138pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC polypeptide, useful for treating cancer, plasma cell disorder, or
CC autoimmune disease. The CAR polypeptide comprises an extracellular domain
CC comprising a target-binding sequence, a transmembrane domain and a co-
CC stimulatory domain. The invention further claims: (1) a mammalian cell
CC comprising: (a) the CAR polypeptide; or (b) a nucleic acid encoding the
CC CAR polypeptide; (2) a method for treating cancer, a plasma cell
CC disorder, or an autoimmune disease in a subject; and (3) a composition
CC comprising the CAR polypeptide and a carrier. The CAR polypeptide of the
CC invention is useful for treating cancer including lymphoma such as B-cell
CC non-Hodgkin lymphoma, mantle cell lymphoma, Burkitt's lymphoma, B cell
CC lymphoblastic lymphoma or T cell lymphoma, peripheral T cell lymphoma,
CC cutaneous T-cell lymphoma or anaplastic large cell lymphoma or leukemia
CC such as acute myeloid leukemia. The present sequence is an anti-CD37/anti
CC -OTK3 single chain variable region (scFv) antibody light chain variable
CC region (VL), used in a CAR polypetide for treating cancer in a subject.
XX
SQ Sequence 108 AA;
RESULT 2
BFM31504
(NOTE: this sequence has 6 duplicates in the database searched.
See complete list at the end of this report)
ID BFM31504 standard; protein; 244 AA.
XX
AC BFM31504;
XX
DT 06-SEP-2018 (first entry)
XX
DE Anti-CD37/anti-OTK3 scFv antibody L-H, SEQ ID 9.
XX
KW CD37; OTK3 protien; acute myelogenous leukemia;
KW anaplastic large cell lymphoma; autoimmune disease;
KW b-cell acute lymphoblastic leukemia; b-cell lymphoma; burkitts lymphoma;
KW cancer; cutaneous t-cell lymphoma; cytostatic; hematological-gen.;
KW immunomodulator; immunosuppressive; immunotherapy; leukemia; lymphoma;
KW mantle cell lymphoma; multiple myeloma; recombinant protein;
KW single chain antibody; t-cell lymphoma; therapeutic.
XX
OS Mus sp.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..108
FT /note= "Light chain variable region"
FT Region 109..128
FT /note= "Linker region"
FT Region 129..244
FT /note= "Heavy chain variable region"
XX
CC PN WO2018132506-A1.
XX
CC PD 19-JUL-2018.
XX
CC PF 10-JAN-2018; 2018WO-US013213.
XX
PR 10-JAN-2017; 2017US-0444605P.
PR 16-MAR-2017; 2017US-0472275P.
PR 01-NOV-2017; 2017US-0580243P.
PR 09-NOV-2017; 2017US-0584060P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Maus MV, Cobbold M, Scarfo I;
XX
DR WPI; 2018-56508P/51.
XX
CC PT New chimeric antigen receptor (CAR) polypeptide comprises e.g.
CC PT extracellular domain comprising a target-binding sequence, a
CC PT transmembrane domain, and co-stimulatory domain, for treating cancer,
CC PT plasma cell disorder, or autoimmune disease.
XX
CC PS Claim 11; SEQ ID NO 9; 138pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC polypeptide, useful for treating cancer, plasma cell disorder, or
CC autoimmune disease. The CAR polypeptide comprises an extracellular domain
CC comprising a target-binding sequence, a transmembrane domain and a co-
CC stimulatory domain. The invention further claims: (1) a mammalian cell
CC comprising: (a) the CAR polypeptide; or (b) a nucleic acid encoding the
CC CAR polypeptide; (2) a method for treating cancer, a plasma cell
CC disorder, or an autoimmune disease in a subject; and (3) a composition
CC comprising the CAR polypeptide and a carrier. The CAR polypeptide of the
CC invention is useful for treating cancer including lymphoma such as B-cell
CC non-Hodgkin lymphoma, mantle cell lymphoma, Burkitt's lymphoma, B cell
CC lymphoblastic lymphoma or T cell lymphoma, peripheral T cell lymphoma,
CC cutaneous T-cell lymphoma or anaplastic large cell lymphoma or leukemia
CC such as acute myeloid leukemia. The present sequence is an anti-CD37/anti
CC -OTK3 single chain variable region (scFv) antibody (light chain variable
CC region-linker-heavy chain variable region, L-H), used in a CAR polypetide
CC for treating cancer in a subject.
XX
SQ Sequence 244 AA;
Query Match 100.0%; Score 567; Length 244;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRTSENVYSYLAWYQQKPGKAPKLLVSSAKTLAEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRTSENVYSYLAWYQQKPGKAPKLLVSSAKTLAEGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQHHSDNPWTFGQGTKVEIKR 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQHHSDNPWTFGQGTKVEIKR 108
Alignment with SEQ ID NO: 12
RESULT 1
BBN94135
(NOTE: this sequence has 23 duplicates in the database searched.
See complete list at the end of this report)
ID BBN94135 standard; protein; 120 AA.
XX
AC BBN94135;
XX
DT 06-NOV-2014 (first entry)
XX
DE Anti-CD19 humanized antibody VH (FMC63_VH_hz3), SEQ ID 116.
XX
KW B-lymphocyte antigen CD19; acute leukemia; acute lymphoblastic leukemia;
KW antibody therapy; b-cell acute lymphoblastic leukemia; burkitts lymphoma;
KW cancer; chronic leukemia; chronic lymphocytic leukemia;
KW chronic myelocytic leukemia; cytostatic; diffuse large b-cell lymphoma;
KW dysplasia; follicle center lymphoma; hairy cell leukemia;
KW heavy chain variable region; hematological neoplasm; hematological-gen.;
KW humanized antibody; lymphoproliferative disease; macroglobulinemia;
KW mantle cell lymphoma; marginal zone b-cell lymphoma; multiple myeloma;
KW myelodysplastic syndrome; neoplasm; non-hodgkin lymphoma; spina bifida;
KW t-cell acute lymphoblastic leukemia; therapeutic.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
XX
FH Key Location/Qualifiers
FT Region 26..33
FT /label= HCDR1
FT /note= "Heavy chain complementary determining region 1
FT according to chothia numbering"
FT Region 31..35
FT /label= HCDR1
FT /note= "Heavy chain complementary determining region 1
FT according to kabat numbering"
FT Region 50..65
FT /label= HCDR2
FT /note= "Heavy chain complementary determining region 2
FT according to kabat numbering"
FT Region 52..56
FT /label= HCDR2
FT /note= "Heavy chain complementary determining region 2
FT according to chothia numbering"
FT Region 95..102
FT /label= HCDR3
FT /note= "Heavy chain complementary determining region 3
FT according to chothia and kabat numbering"
XX
CC PN US2014271635-A1.
XX
CC PD 18-SEP-2014.
XX
CC PF 15-MAR-2014; 2014US-00214728.
XX
PR 16-MAR-2013; 2013US-0802629P.
PR 24-JUN-2013; 2013US-0838537P.
XX
CC PA (UPEN ) UNIV PENNSYLVANIA.
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Brogdon J, June CH, Loew A, Maus M, Scholler J;
XX
DR WPI; 2014-T38977/69.
XX
CC PT New nucleic acid molecule encoding a chimeric antigen receptor comprises
CC PT an antibody including a humanized anti-CD19 binding domain, useful for
CC PT treating a disease expressing CD19 such as proliferative diseases.
XX
CC PS Example 1; SEQ ID NO 116; 166pp; English.
XX
CC The present invention relates to a novel nucleic acid molecule encoding a
CC chimeric antigen receptor (CAR) which is useful for treating a disease
CC expressing CD19. The CAR comprises an antibody or an antibody fragment
CC including a humanized anti-CD19 binding domain. The invention further
CC relates to: (a) an isolated polypeptide molecule encoded by the nucleic
CC acid molecule; (b) an isolated CAR molecule comprising a humanized anti-
CC CD19 binding domain, a transmembrane domain, and an intracellular
CC signaling domain; (c) a humanized anti-CD19 binding domain; (d) a vector
CC comprising a nucleic acid molecule encoding a CAR; (e) a cell comprising
CC the vector; (f) a method for making a cell by transducing a T cell; (f) a
CC method for generating a population of RNA-engineered cells; and (g) a
CC method for providing an anti-tumor immunity in a mammal; and (h) a method
CC of treating a mammal having a disease associated with expression of CD19
CC by administering the cell of comprising a CAR molecule. The disease
CC associated with CD19 expression includes proliferative disease (cancer,
CC malignancy, precancerous condition such as myelodyplasia, myelodyplastic
CC syndrome or preleukemia), hematological cancer (acute leukemias including
CC but not limited to B-cell acute lymphoid leukemia (BALL), T-cell acute
CC lymphoid leukemia (TALL), acute lymphoid leukemia (ALL), chronic
CC leukemias including but not limited to chronic myelogenous leukemia
CC (CML), chronic lymphocytic leukemia (CLL), hematologic cancers or
CC hematologic conditions including B cell prolymphocytic leukemia, blastic
CC plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B
CC cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell-or a
CC large cell-follicular lymphoma, malignant lymphoproliferative conditions,
CC MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple
CC myeloma, non-Hodgkin's lymphoma, plasmablastic lymphoma, dysplasia and
CC Waldenstrom macroglobulinemia). The present sequence represents an anti-
CC CD19 humanized antibody heavy chain variable region (VH) useful in the
CC method of the invention for treating above mentioned diseases of the
CC invention.
XX
SQ Sequence 120 AA;
Query Match 100.0%; Score 634; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQ 60
Qy 61 SSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 120
Alignment with SEQ ID NO: 13
RESULT 1
BBN94136
(NOTE: this sequence has 34 duplicates in the database searched.
See complete list at the end of this report)
ID BBN94136 standard; protein; 107 AA.
XX
AC BBN94136;
XX
DT 06-NOV-2014 (first entry)
XX
DE Anti-CD19 humanized antibody VL (FMC63_VH_hz1), SEQ ID 117.
XX
KW B-lymphocyte antigen CD19; acute leukemia; acute lymphoblastic leukemia;
KW antibody therapy; b-cell acute lymphoblastic leukemia; burkitts lymphoma;
KW cancer; chronic leukemia; chronic lymphocytic leukemia;
KW chronic myelocytic leukemia; cytostatic; diffuse large b-cell lymphoma;
KW dysplasia; follicle center lymphoma; hairy cell leukemia;
KW hematological neoplasm; hematological-gen.; humanized antibody;
KW light chain variable region; lymphoproliferative disease;
KW macroglobulinemia; mantle cell lymphoma; marginal zone b-cell lymphoma;
KW multiple myeloma; myelodysplastic syndrome; neoplasm;
KW non-hodgkin lymphoma; spina bifida; t-cell acute lymphoblastic leukemia;
KW therapeutic.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
XX
FH Key Location/Qualifiers
FT Region 24..34
FT /label= LCDR1
FT /note= "Light chain complementary determining region 1
FT according to kabat numbering"
FT Region 26..32
FT /label= LCDR1
FT /note= "Light chain complementary determining region 1
FT according to chothia numbering"
FT Region 50..56
FT /label= LCDR2
FT /note= "Light chain complementary determining region 2
FT according to kabat numbering"
FT Region 50..52
FT /label= LCDR2
FT /note= "Light chain complementary determining region 2
FT according to chothia numbering"
FT Region 89..97
FT /label= LCDR3
FT /note= "Light chain complementary determining region 3
FT according to kabat numbering"
FT Region 91..96
FT /label= LCDR3
FT /note= "Light chain complementary determining region 3
FT according to chothia numbering"
XX
CC PN US2014271635-A1.
XX
CC PD 18-SEP-2014.
XX
CC PF 15-MAR-2014; 2014US-00214728.
XX
PR 16-MAR-2013; 2013US-0802629P.
PR 24-JUN-2013; 2013US-0838537P.
XX
CC PA (UPEN ) UNIV PENNSYLVANIA.
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Brogdon J, June CH, Loew A, Maus M, Scholler J;
XX
DR WPI; 2014-T38977/69.
XX
CC PT New nucleic acid molecule encoding a chimeric antigen receptor comprises
CC PT an antibody including a humanized anti-CD19 binding domain, useful for
CC PT treating a disease expressing CD19 such as proliferative diseases.
XX
CC PS Example 1; SEQ ID NO 117; 166pp; English.
XX
CC The present invention relates to a novel nucleic acid molecule encoding a
CC chimeric antigen receptor (CAR) which is useful for treating a disease
CC expressing CD19. The CAR comprises an antibody or an antibody fragment
CC including a humanized anti-CD19 binding domain. The invention further
CC relates to: (a) an isolated polypeptide molecule encoded by the nucleic
CC acid molecule; (b) an isolated CAR molecule comprising a humanized anti-
CC CD19 binding domain, a transmembrane domain, and an intracellular
CC signaling domain; (c) a humanized anti-CD19 binding domain; (d) a vector
CC comprising a nucleic acid molecule encoding a CAR; (e) a cell comprising
CC the vector; (f) a method for making a cell by transducing a T cell; (f) a
CC method for generating a population of RNA-engineered cells; and (g) a
CC method for providing an anti-tumor immunity in a mammal; and (h) a method
CC of treating a mammal having a disease associated with expression of CD19
CC by administering the cell of comprising a CAR molecule. The disease
CC associated with CD19 expression includes proliferative disease (cancer,
CC malignancy, precancerous condition such as myelodyplasia, myelodyplastic
CC syndrome or preleukemia), hematological cancer (acute leukemias including
CC but not limited to B-cell acute lymphoid leukemia (BALL), T-cell acute
CC lymphoid leukemia (TALL), acute lymphoid leukemia (ALL), chronic
CC leukemias including but not limited to chronic myelogenous leukemia
CC (CML), chronic lymphocytic leukemia (CLL), hematologic cancers or
CC hematologic conditions including B cell prolymphocytic leukemia, blastic
CC plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B
CC cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell-or a
CC large cell-follicular lymphoma, malignant lymphoproliferative conditions,
CC MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple
CC myeloma, non-Hodgkin's lymphoma, plasmablastic lymphoma, dysplasia and
CC Waldenstrom macroglobulinemia). The present sequence represents an anti-
CC CD19 humanized antibody light chain variable region (VL) useful in the
CC method of the invention for treating above mentioned diseases of the
CC invention.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 561; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPA 60
Qy 61 RFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 107
Alignment with SEQ ID NO: 20
RESULT 1
BBN94025
(NOTE: this sequence has 110 duplicates in the database searched.
See complete list at the end of this report)
ID BBN94025 standard; protein; 247 AA.
XX
AC BBN94025;
XX
DT 06-NOV-2014 (first entry)
XX
DE Humanized anti-CD19 binding domain (CAR6 scFv domain), SEQ ID 6.
XX
KW B-lymphocyte antigen CD19; acute leukemia; acute lymphoblastic leukemia;
KW antibody therapy; b-cell acute lymphoblastic leukemia; burkitts lymphoma;
KW cancer; chronic leukemia; chronic lymphocytic leukemia;
KW chronic myelocytic leukemia; cytostatic; diffuse large b-cell lymphoma;
KW dysplasia; follicle center lymphoma; hairy cell leukemia;
KW hematological neoplasm; hematological-gen.; humanized antibody;
KW lymphoproliferative disease; macroglobulinemia; mantle cell lymphoma;
KW marginal zone b-cell lymphoma; multiple myeloma;
KW myelodysplastic syndrome; neoplasm; non-hodgkin lymphoma; spina bifida;
KW t-cell acute lymphoblastic leukemia; therapeutic.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
XX
CC PN US2014271635-A1.
XX
CC PD 18-SEP-2014.
XX
CC PF 15-MAR-2014; 2014US-00214728.
XX
PR 16-MAR-2013; 2013US-0802629P.
PR 24-JUN-2013; 2013US-0838537P.
XX
CC PA (UPEN ) UNIV PENNSYLVANIA.
CC PA (NOVS ) NOVARTIS AG.
XX
CC PI Brogdon J, June CH, Loew A, Maus M, Scholler J;
XX
DR WPI; 2014-T38977/69.
DR N-PSDB; BBN94085.
XX
CC PT New nucleic acid molecule encoding a chimeric antigen receptor comprises
CC PT an antibody including a humanized anti-CD19 binding domain, useful for
CC PT treating a disease expressing CD19 such as proliferative diseases.
XX
CC PS Claim 11; SEQ ID NO 6; 166pp; English.
XX
CC The present invention relates to a novel nucleic acid molecule encoding a
CC chimeric antigen receptor (CAR) which is useful for treating a disease
CC expressing CD19. The CAR comprises an antibody or an antibody fragment
CC including a humanized anti-CD19 binding domain. The invention further
CC relates to: (a) an isolated polypeptide molecule encoded by the nucleic
CC acid molecule; (b) an isolated CAR molecule comprising a humanized anti-
CC CD19 binding domain, a transmembrane domain, and an intracellular
CC signaling domain; (c) a humanized anti-CD19 binding domain; (d) a vector
CC comprising a nucleic acid molecule encoding a CAR; (e) a cell comprising
CC the vector; (f) a method for making a cell by transducing a T cell; (f) a
CC method for generating a population of RNA-engineered cells; and (g) a
CC method for providing an anti-tumor immunity in a mammal; and (h) a method
CC of treating a mammal having a disease associated with expression of CD19
CC by administering the cell of comprising a CAR molecule. The disease
CC associated with CD19 expression includes proliferative disease (cancer,
CC malignancy, precancerous condition such as myelodyplasia, myelodyplastic
CC syndrome or preleukemia), hematological cancer (acute leukemias including
CC but not limited to B-cell acute lymphoid leukemia (BALL), T-cell acute
CC lymphoid leukemia (TALL), acute lymphoid leukemia (ALL), chronic
CC leukemias including but not limited to chronic myelogenous leukemia
CC (CML), chronic lymphocytic leukemia (CLL), hematologic cancers or
CC hematologic conditions including B cell prolymphocytic leukemia, blastic
CC plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B
CC cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell-or a
CC large cell-follicular lymphoma, malignant lymphoproliferative conditions,
CC MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple
CC myeloma, non-Hodgkin's lymphoma, plasmablastic lymphoma, dysplasia and
CC Waldenstrom macroglobulinemia). The present sequence represents a
CC humanized anti-CD19 binding domain useful in the method of the invention
CC for treating above mentioned diseases of the invention.
XX
SQ Sequence 247 AA;
Query Match 100.0%; Score 1307; Length 247;
Best Local Similarity 100.0%;
Matches 247; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPA 60
Qy 61 RFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGG 120
Qy 121 GSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWG 180
Qy 181 SETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG 240
Qy 241 TLVTVSS 247
|||||||
Db 241 TLVTVSS 247