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 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 30 – 31, 33 – 34, 36 – 37, 39, 41, 45 – 48, 50 – 51, 55, 57 – 62, and 67 – 68 were pending. Claims 1, 5, 7, 12, 14 – 15, 26, 28, 47 – 48, 67 – 68 have been amended, and claim 46 has been canceled. Claims 1 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 30 – 31, 33 – 34, 36 – 37, 39, 41, 45, 47 – 48, 50 – 51, 55, 57 – 62, and 67 – 68 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 10/06/2025 does not fully comply with the requirements of 37 CFR 1.98(b) because: the crossed-out non-patent literature (sheet 48 of the IDS) does not include a valid publication date. A valid publication date is the date the literature became available to the public. Applicant must indicate the date of publication of each reference.
Claim Objections
Previous objection, withdrawn: claims 15, 46 – 48, and 67 were objected to because of informalities.
In view of the claim amendments in the reply of 10/06/2025, this objection is withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Previous rejection, maintained in modified form: claims 1 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 30, 31, 33, 34, 36, 37, 39, 41, 45, 50, 51, 55, and 59 - 62 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
In view of the claim amendments in the reply of 10/06/2025, the rejection of claims 1 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 30 – 31, 33 – 34, 36 – 37, 39, 40, 41, 45, 50, and 59 - 62 is withdrawn.
However, the rejection of claims 51 and 55 is maintained because the number of structures that may possibly read on the claims is an amount that is not supported by the specification. An Fc domain that may be modified at one or more positions selected from the positions recited in claims 51 and 55 leads to a large variety of structures that are not supported by the specification. Under “Exemplary Multi-Specific Binding Proteins” (p. 84 – 95), several TriNKETs with specific Fc domains are described; however, they do not cover the large number of proteins that may result from the limitations of present claims 51 and 55.
In view of the variety of possible protein structures that may result from the limitations of claims 51 and 55 and the absence of a representative number of examples, claims 51 and 55 are rejected for lack of adequate written description support.
Previous rejection, withdrawn: claim 68 was rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
In view of the claim amendments in the reply of 10/06/2025, this rejection is withdrawn.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Previous rejection, withdrawn: claims 1 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 36, 50, 51, 55, 59, 62, and 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20, 22 - 39, 44, and 57 – 59 of copending Application No. 17/769,257 in view of Durben et al, WO2013092001A1, published June 27, 2013.
In view of the claim amendments in the reply of 10/06/2025, this rejection is withdrawn.
New rejection, necessitated by claim amendments: Claims 1 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 30 – 31, 33 – 34, 36 – 37, 39, 41, 45, 47 – 48, 50 – 51, 55, 59 – 62, and 67 – 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 4, 6 – 8, 11 – 13, 21 – 22, 24, 26, 28 – 32, 34, 38, 40, 42, 44 – 46, 50 – 52, 57 – 58, and 63 of copending Application No. 17/769,257 in view of CHANG (WO/2018148566-A1, published 08/16/2018; see IDS submitted 10/06/2025, p. 26).
Copending claim 1 recites an antigen-binding site that binds FLT3, comprising:(a) a heavy chain variable domain (VH) comprising complementarity-determining region 1 (CDR1), complementarity-determining region 2 (CDR2), and complementarity-determining region 3 (CDR3) comprising the amino acid sequences of SEQ ID NOs: 11, 4, and 55, respectively; and (b) a light chain variable domain (VL) comprising CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs: 6, 7, and 8, respectively.
The VH CDRs of copending SEQ ID NOs: 11, 4, and 55 are identical to those with the same SEQ ID NOs of present claim 1. The VL CDRs of copending SEQ ID NOs: 6, 7, and 8 are identical to those with the same SEQ ID NOs of present claim 1. See Appendix.
Copending claim 58 recites that the anti-FLT3 protein treats cancer and that FLT3 is expressed by cancer cells. Thus, the copending claims teach that FLT3 is a cancer-associated antigen.
The main difference between the present claims and the copending claims is that the present claims recite:
a first antigen-binding site that binds NKG2D which comprises a VH comprising CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ IDNOs: 240 or 241, 242, and 270 or 271, respectively; and a VL comprising CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs: 276, 236, and 245, respectively, and
an antibody Fc domain or a portion thereof sufficient to bind CD 16.
However, CHANG discloses this difference.
CHANG is directed to a protein comprising: (a) a first antigen-binding site that binds NKG2D; (b) a second antigen-binding site that binds BCMA; and (c) an antibody Fc domain or a portion thereof sufficient to bind CD16, or a third antigen-binding site that binds CD 16. See claim 1.
CHANG teaches the NKG2D CDRs of SEQ ID NOs: 240, 242, 270, 276, 236, and 245 with 100% identity. See Appendix.
CHANG teaches trispecific binding proteins (TriNKETs) that each contain an NKG2D-binding domain, a tumor-associated antigen-binding domain (BCMA-binding domain), and an Fc domain that binds to CD 16. See paragraph 00181. Furthermore, CHANG teaches that "tumor associated antigen" means any antigen including but not limited to a protein, glycoprotein, ganglioside, carbohydrate, lipid that is associated with cancer and that such antigen can be expressed on malignant cells or in the tumor
microenvironment such as on tumor-associated blood vessels, extracellular matrix, mesenchymal stroma, or immune infiltrates. See paragraph 0063. Thus, CHANG suggests that the BCMA-binding domain may be replaced with another tumor-associated antigen.
Therefore, because CHANG teaches a protein that binds NKG2D, a tumor-associated antigen, and CD16 to enhance tumor cell death in the treatment of cancer and the copending claims recite a protein that the tumor-associated antigen FLT3 for the treatment of cancer, it would have been obvious to one having ordinary skill in the art to use the copending claims’ FLT3-binding CDRs instead of the BCMA-binding CDRs in CHANG’s protein structure to arrive to the present invention. There would have been a reasonable expectation of success considering that a protein comprising a first antigen-binding site that binds NKG2D, a second antigen-binding site that binds a tumor antigen (such as FLT3, which the copending claims disclose as a target in the treatment of cancer), and an antibody Fc domain that binds CD16 is known to successfully treat cancer, as evidenced by the applied prior art.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claims 57 and 58 are allowed.
Claims 57 and 58 each recites a structure with sequences that are free of the art.
Conclusion
Claims 1 – 3, 5, 7 – 10, 12, 14 – 16, 24, 26, 28, 30 – 31, 33 – 34, 36 – 37, 39, 41, 45, 47 – 48, 50 – 51, 55, 59 – 62, and 67 – 68 are rejected. Claims 57 and 58 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 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 M. GUSTILO whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:00 AM - 5:00 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
Copending application 17769257 aligned to instantly claimed SEQ ID NO: 11-4-55
RESULT 2
US-17-769-257-58
Filing date in PALM: 2022-04-14
Sequence 58, US/17769257
Publication No. US20240228628A9
GENERAL INFORMATION
APPLICANT: DRAGONFLY THERAPEUTICS, INC.
TITLE OF INVENTION: ANTIBODIES TARGETING FLT3 AND USE THEREOF
FILE REFERENCE: 14247-473-999
APPLICANT: DRAGONFLY THERAPEUTICS, INC.
TITLE OF INVENTION: PROTEINS BINDING NKG2D, CD16 AND FLT3
CURRENT APPLICATION NUMBER: US/17/769,160
Query Match 78.9%; Score 97; Length 118;
Best Local Similarity 26.8%;
Matches 22; Conservative 0; Mismatches 0; Indels 60; Gaps 2;
Qy 1 GYTFTRY-------------------NPYNDD---------------------------- 13
||||||| ||||||
Db 26 GYTFTRYVXHWVRQAPGQCLEWMGFINPYNDDTKYNEKFKGRVTITRDTSASTAYMELSS 85
Qy 14 -------------WRQLGSLXS 22
|||||||||
Db 86 LRSEDTAVYYCARWRQLGSLXS 107
Copending application 17769257 aligned to instantly claimed SEQ ID NO: 6-7-8
ALIGNMENT:
Query Match 84.8%; Score 137.3; Length 111;
Best Local Similarity 39.7%;
Matches 31; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASESVDTYGSSFVH---------------LASNLES----------------------- 22
||||||||||||||| |||||||
Db 24 RASESVDTYGSSFVHWYQQKPGQPPKLLIYLASNLESGVPDRFSGSGSRTDFTLTISSLQ 83
Qy 23 ---------QQNNEEPWT 31
|||||||||
Db 84 AEDAAVYYCQQNNEEPWT 101
DUPLICATES:
US-17-769-257-34
Filing date in PALM: 2022-04-14
Sequence 34, US/17769257
Publication No. US20240228628A9
GENERAL INFORMATION
APPLICANT: DRAGONFLY THERAPEUTICS, INC.
TITLE OF INVENTION: ANTIBODIES TARGETING FLT3 AND USE THEREOF
FILE REFERENCE: 14247-473-999
CURRENT APPLICATION NUMBER: US/17/769,257
CURRENT FILING DATE: 2022-04-14
PRIOR APPLICATION NUMBER: PCT/US2020/055480
PRIOR FILING DATE: 2020-10-14
PRIOR APPLICATION NUMBER: 62/915,120
PRIOR FILING DATE: 2019-10-15
NUMBER OF SEQ ID NOS: 146
SEQ ID NO 34
Alignment with SEQ ID NOs: 240, 242, and 270
RESULT 2
BFP36465
(NOTE: this sequence has 40 duplicates in the database searched.
See complete list at the end of this report)
ID BFP36465 standard; protein; 122 AA.
XX
AC BFP36465;
XX
DT 04-OCT-2018 (first entry)
XX
DE Anti-NKG2D monoclonal antibody (ADI-27749 (A49)) VH region, SEQ 101.
XX
KW NKG2D ligand; acute myelogenous leukemia; antibody therapy;
KW apoptosis stimulation; cancer; cytostatic; expression;
KW follicle center lymphoma; heavy chain variable region;
KW monoclonal antibody; multiple myeloma; t-cell lymphoma; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2018148566-A1.
XX
CC PD 16-AUG-2018.
XX
CC PF 09-FEB-2018; 2018WO-US017653.
XX
PR 10-FEB-2017; 2017US-0457780P.
XX
CC PA (ADIM-) ADIMAB LLC.
XX
CC PI Chang GP, Cheung AF, Haney W, Lunde BM, Prinz B;
XX
DR WPI; 2018-63737S/56.
XX
CC PT New protein comprising natural killer group 2D binding site, B-cell
CC PT maturation antigen binding site, and antibody fragment crystallizable
CC PT domain or third antigen-binding site that binds cluster of
CC PT differentiation (CD)16 used to treat cancer.
XX
CC PS Disclosure; SEQ ID NO 101; 82pp; English.
XX
CC The present invention relates to a novel protein, useful for treating
CC cancer in a patient. The protein preferably an antibody comprises a first
CC antigen-binding site specifically binding to a NKG2D, second antigen-
CC binding site specifically binding to a B-cell maturation antigen (BCMA),
CC and antigen Fc domain binding to a CD16 or a third antigen-binding site
CC specifically binding to the CD16. The antibody comprises a heavy chain
CC variable region (VH) and light chain variable region (VL) with their
CC corresponding complementarity determining regions (CDRs). The invention
CC further claims: (1) a formulation comprising the novel protein; (2) a
CC cell comprising a nucleic acid expressing the protein; (3) a method for
CC directly and/or indirectly enhancing tumor cell death; and (4) a method
CC for treating cancer by administering the formulation comprising the
CC protein to the patient. The protein is useful for treating cancer such as
CC multiple myeloma, acute myelomonocytic leukemia, T-cell lymphoma, acute
CC monocytic leukemia, and follicular lymphoma. The protein exhibits
CC synergistic effect in treating cancer and has reduced tumor side effects
CC and useful for enhancing tumor cell death by exposing tumor and natural
CC killer (NK) cells to the protein. The present sequence is an anti-NKG2D
CC monoclonal antibody VH region, which can be useful for treating cancer in
CC the method of the present invention.
XX
SQ Sequence 122 AA;
Query Match 88.4%; Score 185.6; Length 122;
Best Local Similarity 47.1%;
Matches 40; Conservative 1; Mismatches 0; Indels 44; Gaps 2;
Qy 1 FTFSSYSMN--------------SISSSSSYIYYADSVKG-------------------- 26
||||||||| |||||||||||||||||
Db 27 FTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSL 86
Qy 27 ----------ARGAPXGAAAGWFDP 41
|||||:|||||||||
Db 87 RAEDTAVYYCARGAPMGAAAGWFDP 111
RESULT 2
BFP36466
(NOTE: this sequence has 40 duplicates in the database searched.
See complete list at the end of this report)
ID BFP36466 standard; protein; 107 AA.
XX
AC BFP36466;
XX
DT 04-OCT-2018 (first entry)
XX
DE Anti-NKG2D monoclonal antibody (ADI-27749 (A49)) VL region, SEQ 102.
XX
KW NKG2D ligand; acute myelogenous leukemia; antibody therapy;
KW apoptosis stimulation; cancer; cytostatic; expression;
KW follicle center lymphoma; light chain variable region;
KW monoclonal antibody; multiple myeloma; t-cell lymphoma; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2018148566-A1.
XX
CC PD 16-AUG-2018.
XX
CC PF 09-FEB-2018; 2018WO-US017653.
XX
PR 10-FEB-2017; 2017US-0457780P.
XX
CC PA (ADIM-) ADIMAB LLC.
XX
CC PI Chang GP, Cheung AF, Haney W, Lunde BM, Prinz B;
XX
DR WPI; 2018-63737S/56.
XX
CC PT New protein comprising natural killer group 2D binding site, B-cell
CC PT maturation antigen binding site, and antibody fragment crystallizable
CC PT domain or third antigen-binding site that binds cluster of
CC PT differentiation (CD)16 used to treat cancer.
XX
CC PS Disclosure; SEQ ID NO 102; 82pp; English.
XX
CC The present invention relates to a novel protein, useful for treating
CC cancer in a patient. The protein preferably an antibody comprises a first
CC antigen-binding site specifically binding to a NKG2D, second antigen-
CC binding site specifically binding to a B-cell maturation antigen (BCMA),
CC and antigen Fc domain binding to a CD16 or a third antigen-binding site
CC specifically binding to the CD16. The antibody comprises a heavy chain
CC variable region (VH) and light chain variable region (VL) with their
CC corresponding complementarity determining regions (CDRs). The invention
CC further claims: (1) a formulation comprising the novel protein; (2) a
CC cell comprising a nucleic acid expressing the protein; (3) a method for
CC directly and/or indirectly enhancing tumor cell death; and (4) a method
CC for treating cancer by administering the formulation comprising the
CC protein to the patient. The protein is useful for treating cancer such as
CC multiple myeloma, acute myelomonocytic leukemia, T-cell lymphoma, acute
CC monocytic leukemia, and follicular lymphoma. The protein exhibits
CC synergistic effect in treating cancer and has reduced tumor side effects
CC and useful for enhancing tumor cell death by exposing tumor and natural
CC killer (NK) cells to the protein. The present sequence is an anti-NKG2D
CC monoclonal antibody VL region, which can be useful for treating cancer in
CC the method of the present invention.
XX
SQ Sequence 107 AA;
Query Match 81.1%; Score 106.3; Length 107;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASQGISSWLA---------------AASSLQS--------------------------- 18
||||||||||| |||||||
Db 24 RASQGISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----QQGVSFPRT 27
|||||||||
Db 84 ATYYCQQGVSFPRT 97
Alignment with SEQ ID NOs: 276, 236, 245
RESULT 2
BFP36466
(NOTE: this sequence has 40 duplicates in the database searched.
See complete list at the end of this report)
ID BFP36466 standard; protein; 107 AA.
XX
AC BFP36466;
XX
DT 04-OCT-2018 (first entry)
XX
DE Anti-NKG2D monoclonal antibody (ADI-27749 (A49)) VL region, SEQ 102.
XX
KW NKG2D ligand; acute myelogenous leukemia; antibody therapy;
KW apoptosis stimulation; cancer; cytostatic; expression;
KW follicle center lymphoma; light chain variable region;
KW monoclonal antibody; multiple myeloma; t-cell lymphoma; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2018148566-A1.
XX
CC PD 16-AUG-2018.
XX
CC PF 09-FEB-2018; 2018WO-US017653.
XX
PR 10-FEB-2017; 2017US-0457780P.
XX
CC PA (ADIM-) ADIMAB LLC.
XX
CC PI Chang GP, Cheung AF, Haney W, Lunde BM, Prinz B;
XX
DR WPI; 2018-63737S/56.
XX
CC PT New protein comprising natural killer group 2D binding site, B-cell
CC PT maturation antigen binding site, and antibody fragment crystallizable
CC PT domain or third antigen-binding site that binds cluster of
CC PT differentiation (CD)16 used to treat cancer.
XX
CC PS Disclosure; SEQ ID NO 102; 82pp; English.
XX
CC The present invention relates to a novel protein, useful for treating
CC cancer in a patient. The protein preferably an antibody comprises a first
CC antigen-binding site specifically binding to a NKG2D, second antigen-
CC binding site specifically binding to a B-cell maturation antigen (BCMA),
CC and antigen Fc domain binding to a CD16 or a third antigen-binding site
CC specifically binding to the CD16. The antibody comprises a heavy chain
CC variable region (VH) and light chain variable region (VL) with their
CC corresponding complementarity determining regions (CDRs). The invention
CC further claims: (1) a formulation comprising the novel protein; (2) a
CC cell comprising a nucleic acid expressing the protein; (3) a method for
CC directly and/or indirectly enhancing tumor cell death; and (4) a method
CC for treating cancer by administering the formulation comprising the
CC protein to the patient. The protein is useful for treating cancer such as
CC multiple myeloma, acute myelomonocytic leukemia, T-cell lymphoma, acute
CC monocytic leukemia, and follicular lymphoma. The protein exhibits
CC synergistic effect in treating cancer and has reduced tumor side effects
CC and useful for enhancing tumor cell death by exposing tumor and natural
CC killer (NK) cells to the protein. The present sequence is an anti-NKG2D
CC monoclonal antibody VL region, which can be useful for treating cancer in
CC the method of the present invention.
XX
SQ Sequence 107 AA;
Query Match 81.1%; Score 106.3; Length 107;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASQGISSWLA---------------AASSLQS--------------------------- 18
||||||||||| |||||||
Db 24 RASQGISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----QQGVSFPRT 27
|||||||||
Db 84 ATYYCQQGVSFPRT 97