Office Action 1: Non-Final Rejection (2024-09-12)
Rejection types: 112 - Written Description/Enablement, Double Patenting

CLAIMS:
AMENDMENTS TO THE CLAIMS

Ple .se enter the following amendments into the subject application.

USSN: 18/164,444

1\. - 34. (Canceled)233

35\. (New) A cell penetrating antibody that binds to DNA, wherein the antibody comprises:- a heavy chain variable region (VH) comprising:
a complementarity determining region (CDR) 1 comprising the sequence NYGMH (SEQ ID NO: 1),
a CDR2 comprising the sequence YISSGSSTIYYADSVKG (SEQ ID NO: 3), and a CDR3 comprising the sequence RGLLLDY (SEQ ID NO: 4); and- a light chain variable region (VL) comprising:
a CDR1 comprising the sequence RASKTVSTSSYSYMH (SEQ ID NO: 6), a CDR2 comprising the sequence YASYLES (SEQ ID NO: 7), and a CDR3 comprising the sequence QHSREFPWT (SEQ ID NO: 8), wherein the antibody is conjugated to a therapeutic compound.

36\. (New) The antibody of claim 35, wherein:(i) the VHcomprises a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 21 to 23; and
(ii) the VL comprises a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 27 to 29.

37\. (New) The antibody of claim 35, wherein the therapeutic compound comprises a cytotoxic agent.

38\. (New) The antibody of claim 35, wherein the therapeutic compound comprises a che rotherapeutic agent.

39\. (New) The antibody of claim 35, wherein the therapeutic compound comprises an anti- inflammatory agent.
USSN: 18/164,444

40\. (New) The antibody of claim 35, wherein the therapeutic compound comprises a radioisotope.

41\. (New) A composition comprising:the antibody of claim 35; and
a pharmaceutically acceptable carrier.

42\. (New) A method of treating cancer in a subject, the method comprising administering to the subject an effective amount of the antibody of claim 35.

43\. (New) The method of claim 42, wherein the cancer is glioblastoma.

44\. (New) The method of claim 42, wherein the cancer is substantially BRCA2 deficient.

45\. (New) The method of claim 42, wherein the cancer is substantially PTEN deficient.

46\. (New) A cell penetrating antibody that binds to DNA, wherein the antibody comprises:- a heavy chain variable region (VH) comprising:
a complementarity determining region (CDR) 1 comprising the sequence NYGMH (SEQ ID NO: 1),
a CDR2 comprising the sequence YISSGSSTIYYADSVKG (SEQ ID NO: 3), and a CDR3 comprising the sequence RGLLLDY (SEQ ID NO: 4); and- a light chain variable region (VL) comprising:
a CDR1 comprising the sequence RASKTVSTSSYSYMH (SEQ ID NO: 6), a CDR2 comprising the sequence YASYLES (SEQ ID NO: 7), and a CDR3 comprising the sequence QHSREFPWT (SEQ ID NO: 8), wherein the antibody is conjugated to a nucleic acid.

47\. (New) The antibody of claim 46, wherein:(i) the VH comprises a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 21 to 23; and
(ii) the VL comprises a sequence at least 95% identical to the sequence as shown in
USSN: 18/164,444 any one of SEQ ID NOs: 27 to 29.

48\. (New) A composition comprising:the antibody of claim 46; and
a pharmaceutically acceptable carrier.

49\. (New) A method of treating cancer in a subject, the method comprising administering to the subject an effective amount of the antibody of claim 46.

50\. (New) The method of claim 49, wherein the cancer is glioblastoma.

51\. (New) The method of claim 49, wherein the cancer is substantially BRCA2 deficient.

52\. (New) The method of claim 49, wherein the cancer is substantially PTEN deficient.

OFFICE ACTION:
DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 35-52 are pending.
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 35 and 46 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA  35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 35 and 46  the parentheses renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.  See MPEP § 2173.05(d).
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.
Claims 35-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No.11,613,590. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to a cell penetrating anti-DNA binding protein having an (iv) a Fab;
antigen binding domain, wherein the antigen binding domain binds to DNA and comprises: a heavy chain variable region (VH) having a CDR1 as shown in SEQ ID NO: 1, a CDR2 as shown in SEQ ID NO: 3 and a CDR3 as shown in SEQ ID NO: 4; and a VL having a CDR1 as shown in SEQ ID NO: 6, a CDR2 as shown in SEQ ID NO: 7 and a CDR3 as shown in SEQ ID NO: 8, which is conjugated to another compound and methods of treating cancer with the cell penetrating anti-DNA binding protein. The specification discloses that the antibody may be conjugated to a toxic compound such as a cytotoxic agents, chemotherapeutic agents and radiolabel (page 12, line 5-25; page 43, lines 1-12). Thus, the present claims and the claims of U.S. Patent No.11,613,590 overlap in scope. It is noted that the present application is a continuation of  U.S. Patent No.11,613,590.
Claims 35-52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-15 and 17-21 of copending Application No. 18561018. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of copending Application No. 18561018 are drawn to the antibody drug conjugate of claim 5, wherein the antibody comprises:
(i) a VH comprising a sequence as shown in SEQ ID NO:7 or SEQ ID NO: 17 or SEQ
ID NO: 18 or SEQ ID NO: 19 and a VL comprising a sequence as shown in SEQ ID NO: 8 or SEQ ID NO: 14 or SEQ NO: 15 or SEQ ID NO: 16 and methods of diagnosing and treating brain cancer with the antibody drug conjugate. As disclosed below, the claimed antibody having a CDR1 as shown in SEQ ID NO: 1, a CDR2 as shown in SEQ ID NO: 3 and a CDR3 as shown in SEQ ID NO: 4; and a VL having a CDR1 as shown in SEQ ID NO: 6, a CDR2 as shown in SEQ ID NO: 7 and a CDR3 as shown in SEQ ID NO: 8 encompasses an antibody comprising a VH comprising SEQ ID NO:18 and a VL region comprising SEQ ID NO: 15. Thus, the claims of copending Application No. 18561018 overlap with the present claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US-18-561-018-18
Sequence 18, US/18561018
Publication No.  US20240226316A1
GENERAL INFORMATION
APPLICANT:  Transmab Pty Ltd
TITLE OF INVENTION:  Improved Immunoglobulin I
FILE REFERENCE:  2953220.001201
CURRENT APPLICATION NUMBER:  US/18/561,018
CURRENT FILING DATE:  2023-11-15
PRIOR APPLICATION NUMBER:  PCT/AU2022/050503
PRIOR FILING DATE:  2022-05-25
PRIOR APPLICATION NUMBER:  AU 2021901567
PRIOR FILING DATE:  2021-05-25
NUMBER OF SEQ ID NOS: 21
SEQ ID NO  18
LENGTH:  116
TYPE:  PRT
ORGANISM:  Artificial Sequence
FEATURE:
OTHER INFORMATION:  Heavy chain (VH) of DX3 variant 2
Query Match             83.9%;  Score 128.4;  Length 116;
Best Local Similarity   38.7%;
Matches   29;  Conservative    0;  Mismatches    0;  Indels   46;  Gaps    2;
Qy          1 NYGMH--------------YISSGSSTIYYADSVKG------------------------ 22
|||||              |||||||||||||||||
Db         31 NYGMHWVRQAPGKGLEWVSYISSGSSTIYYADSVKGRYTISRENAKNSLYLQMNSLRAED 90
Qy         23 --------RGLLLDY 29
|||||||
Db         91 TGMYYCARRGLLLDY 105
US-18-561-018-15
Sequence 15, US/18561018
Publication No.  US20240226316A1
GENERAL INFORMATION
APPLICANT:  Transmab Pty Ltd
TITLE OF INVENTION:  Improved Immunoglobulin I
FILE REFERENCE:  2953220.001201
CURRENT APPLICATION NUMBER:  US/18/561,018
CURRENT FILING DATE:  2023-11-15
PRIOR APPLICATION NUMBER:  PCT/AU2022/050503
PRIOR FILING DATE:  2022-05-25
PRIOR APPLICATION NUMBER:  AU 2021901567
PRIOR FILING DATE:  2021-05-25
NUMBER OF SEQ ID NOS: 21
SEQ ID NO  15
LENGTH:  111
TYPE:  PRT
ORGANISM:  Artificial Sequence
FEATURE:
OTHER INFORMATION:  Light chain (VL) of DX3 variant 2
Query Match             85.1%;  Score 141.3;  Length 111;
Best Local Similarity   39.7%;
Matches   31;  Conservative    0;  Mismatches    0;  Indels   47;  Gaps    2;
Qy          1 RASKTVSTSSYSYMH---------------YASYLES----------------------- 22
|||||||||||||||               |||||||
Db         24 RASKTVSTSSYSYMHWYQQKPGQPPKLLIKYASYLESGVPSRFSGSGSGTDYTLQINSLQ 83
Qy         23 ---------QHSREFPWT 31
|||||||||
Db         84 PEDAANYYCQHSREFPWT 101
Summary
No claims allowed.


NEXT OFFICE ACTION: DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 35-52 are pending and under examination.
35 USC § 112 rejections withdrawn
Upon review and reconsideration the rejections of claims 35 and 46 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter are withdrawn.
Double Patenting rejections withdrawn
The rejections of claims 35-52 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No.11,613,590 are withdrawn in view of Applicant’s filing of a terminal disclaimer.
The rejections of claims 35-52 on the ground of nonstatutory double patenting as being unpatentable over claim 1-15 and 17-21 of copending Application No. 18561018 are withdrawn in view of Applicant’s argument that the present application has an earlier patent term filing date and the application is in condition of allowance with the ODP as the remaining rejection.g date and permit that application to issue as a    patent
REASONS FOR ALLOWANCE
The following is an examiner’s statement of reasons for allowance:
Claims 35-52 are found to be allowable because the art does not disclose or make obvious a cell penetrating antibody that binds to DNA, comprising a heavy chain variable region (VH) comprising: a complementarity determining region (CDR) 1 comprising the sequence NYGMH (SEQ ID NO: 1), a CDR2 comprising the sequence YISSGSSTIYY ADSVKG (SEQ ID NO: 3), and a CDR3 comprising the sequence RGLLLDY (SEQ ID NO: 4); and a light chain variable region (VL) comprising: a CDR1 comprising the sequence RASKTVSTSSYSYMH (SEQ ID NO: 6), a CDR2 comprising the sequence YASYLES (SEQ ID NO: 7), and a CDR3 comprising the sequence QHSREFPWT (SEQ ID NO: 8), wherein the antibody is conjugated to a therapeutic compound.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”

CITED REFERENCE SUMMARIES: Ref US11613590: Claims:
1. A cell penetrating anti-DNA binding protein having an antigen binding domain, wherein the antigen binding domain binds to DNA and comprises:
a heavy chain variable region (VH) having a complementarity determining region (CDR) 1 as shown in SEQ ID NO: 1, a CDR2 as shown in SEQ ID NO: 3 and a CDR3 as shown in SEQ ID NO: 4; and
a light chain variable region (VL) having a CDR1 as shown in SEQ ID NO: 6, a CDR2 as shown in SEQ ID NO: 7 and a CDR3 as shown in SEQ ID NO: 8.
2. The binding protein of claim 1 comprising:
(i) a VH comprising a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 21 to 23;
(ii) a VL comprising a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 27 to 29; or
(iii) a VH comprising a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 21 to 23 and a VL comprising a sequence at least 95% identical to the sequence as shown in any one of SEQ ID NOs: 27 to 29.
3. The binding protein according to claim 1, wherein the VH and a VL are separated by a linker which comprises the sequence shown in SEQ ID NO: 30.
4. The binding protein of claim 1, wherein, the VH and VL are in a single polypeptide chain.
5. The binding protein of claim 4, which is:
(i) a single chain Fv fragment (scFv);
(ii) a dimeric scFv (di-scFv);
(iii) a trimeric scFv (tri-scFv); or
(iv) any one of (i), (ii) or (iii) linked to a constant region of an antibody, Fc or a heavy chain constant domain CH 2 and/or CH 3.
6. The binding protein of claim 4, which is a scFv.
7. The binding protein of claim 4, which is a di-scFv.
8. The binding protein according to claim 1, wherein, the VH and VL are in a separate polypeptide chain.
9. The binding protein of claim 8, which is:
(i) a diabody;
(ii) a triabody;
(iii) a tetrabody;
(iv) a Fab;
(v) a F(ab')2;
(vi) a Fv; or
(vii) one of (i) to (vi) linked to a constant region of an antibody, Fc or a heavy chain constant domain CH 2 and/or CH 3; or,
(viii) an antibody.
10. The binding protein according to claim 1, which comprises an amino acid sequence as shown in any one of SEQ ID NOs: 41-47.
11. The binding protein of claim 1, which is conjugated to another compound.
12. The binding protein of claim 1, wherein the VH comprises a sequence at least 99% identical to the sequence as shown in SEQ ID NO: 21 and the VL comprises a sequence at least 99% identical to the sequence as shown in SEQ ID NO: 27.
13. The binding protein of claim 1, wherein the VH comprises the sequence shown in SEQ ID NO: 21 and the VL comprises the sequence shown in SEQ ID NO: 27.
14. A nucleic acid encoding a binding protein defined by claim 1.
15. An expression construct or recombinant cell comprising a nucleic acid defined by claim 14.
16. A method of treating cancer in a subject, the method comprising administering to the subject and effective amount of a binding protein defined claim 1.
17. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a binding protein or Fv fragment defined by claim 1 and a PARP inhibitor.
18. The method of claim 17, wherein the PARP inhibitor is olaparib.
19. The method of claim 17, wherein the cancer is substantially HDR deficient, substantially BRCA2 deficient, substantially PTEN deficient or resistant to PARP inhibition.
20. The method of claim 17, wherein the cancer is colon cancer, brain cancer, prostate, ovarian, breast, endometrial, melanoma, or pancreatic cancer, a triple negative breast cancer or glioblastoma.
Ref US20240226316A1: Claims:
1. A method of delivering a payload to the brain of a human subject, the method comprising administering to the subject a cell-penetrating, anti-DNA antibody conjugated to a payload, wherein the antibody is an IgG, humanized and comprises:
a heavy chain variable region (VH) having a complementarity determining region (CDR) 1 as shown in SEQ ID NO: 1 or SEQ ID NO: 12, a CDR2 as shown in SEQ ID NO:2 or SEQ ID NO: 13 and a CDR3 as shown in SEQ ID NO: 3; and a light chain variable region (VL) having a CDR1 as shown in SEQ ID NO: 4 or SEQ ID NO: 11, a CDR2 as shown in SEQ ID NO: 5 and a CDR3 as shown in SEQ ID NO: 6 and wherein the subject does not have cancer.
2. A method of delivering a payload to the brain of a human subject, the method comprising administering to the subject a cell-penetrating, anti-DNA antibody conjugated to a payload, wherein the antibody is an IgG, humanized and comprises:
a heavy chain variable region (VH) having a complementarity determining region (CDR) 1 as shown in SEQ ID NO: 1 or SEQ ID NO: 12, a CDR2 as shown in SEQ ID NO:2 or SEQ ID NO: 13 and a CDR3 as shown in SEQ ID NO: 3; and a light chain variable region (VL) having a CDR1 as shown in SEQ ID NO: 4 or SEQ ID NO: 11, a CDR2 as shown in SEQ ID NO: 5 and a CDR3 as shown in SEQ ID NO: 6 and wherein the subject has an intact blood brain barrier.
3. The method of any one of claim 1 or claim 2, wherein the antibody comprises:
(i) a VH comprising a sequence at least 90% identical to the sequence as shown in SEQ ID NO: 7 or SEQ ID NO: 17 or SEQ ID NO: 18 or SEQ ID NO: 19 and, a VL comprising a sequence at least 90% identical to the sequence as shown in SEQ ID NO: 8 or SEQ ID NO: 14 or SEQ NO: 15 or SEQ ID NO: 16; or, (ii) a VH comprising a sequence at least 90% identical to the sequence as shown in SEQ ID NO: 7 and, a VL comprising a sequence at least 90% identical to the sequence as shown in SEQ ID NO: 8.
4. The method of claim 3, wherein the antibody comprises a heavy chain comprising a sequence set forth in SEQ ID NO: 9 and a light chain comprising a sequence set forth in SEQ ID NO: 10.
5. A pharmaceutical composition comprising a cell-penetrating anti-DNA antibody conjugated to a payload, wherein the antibody is an IgG, humanized and comprises a VH having a CDR1 as shown in SEQ ID NO: 1 or SEQ ID NO: 12, a CDR2 as shown in SEQ ID NO: 2 or SEQ ID NO: 13 and a CDR3 as shown in SEQ ID NO: 3; and a VL having a CDR1 as shown in SEQ ID NO: 4 or SEQ ID NO: 11, a CDR2 as shown in SEQ ID NO: 5 and a CDR3 as shown in SEQ ID NO: 6.
6. The pharmaceutical composition of claim 5, wherein the antibody comprises:
(i) a VH comprising a sequence as shown in SEQ ID NO:7 or SEQ ID NO: 17 or SEQ ID NO: 18 or SEQ ID NO: 19 and a VL comprising a sequence as shown in SEQ ID NO: 8 or SEQ ID NO: 14 or SEQ NO: 15 or SEQ ID NO: 16; or (ii) a VH comprising a sequence as shown in SEQ ID NO:7 and a VL comprising a sequence as shown in SEQ ID NO: 8.
7. The method of any one of claims 1-4 or the composition of claim 5 or claim 6, wherein the antibody comprises a heavy chain variable region (VH) having a complementarity determining region (CDR) 1 as shown in SEQ ID NO: 1, a CDR2 as shown in SEQ ID NO:2 and a CDR3 as shown in SEQ ID NO: 3; and a light chain variable region (VL) having a CDR1 as shown in SEQ ID NO: 4, a CDR2 as shown in SEQ ID NO: 5 and a CDR3 as shown in SEQ ID NO: 6.
8. The method or the composition of claim 7, wherein the antibody comprises a VH comprising a sequence as shown in SEQ ID NO: 7 and a VL comprising a sequence as shown in SEQ ID NO: 8.
9. The method of any one of claims 1-4 or 7-8 or the composition of any one of claims 5-8, wherein the payload is a therapeutic payload.
10. The method or the composition of claim 9, wherein the therapeutic payload treats a condition affecting the brain of the subject.
11. The method or the composition of claim 10, wherein the condition is neurological disorder, a psychiatric disorder or a neurodegenerative disorder.
12. The method or the composition of any one of claims 9-11, wherein the therapeutic payload is selected from the group consisting of: a nucleic acid, an anti-psychotic, an anti-depressant, an anti-inflammatory, an anti-neurodegenerative disease agent, a mood-stabilizer and an immunosuppressive agent.
13. The method of any one of claims 1-4 or 7-8 or the composition of any one of claims 5-8, wherein the payload is a diagnostic agent.
14. The method or the composition of claim 13, wherein the diagnostic agent is selected from the group consisting of: a radio pharmaceutical, an imaging agent and a nanoparticle.
15. A method of treating a condition affecting the brain of a human subject, the method comprising administering to the subject the composition of any one of claims 7-12, wherein the subject does not have cancer.
16. Use of the composition of any one of claims 7-12 in the manufacture of a medicament for treating a condition affecting the brain of a subject, wherein the subject does not have cancer.
17. The method of any one of claims 1-4 or 7-12 or the use of claim 16, wherein the cancer is brain cancer.
18. The method or the use of claim 15, wherein the brain cancer is glioblastoma.
19. The method of any one of claims 1-4, 7-15 or 17-18 or the use of any one of claims 16-18, wherein the subject's blood brain barrier is intact.
20. The method of any one of claims 1-4 or 7-8 or the composition of any one of claims 5-8, wherein the payload is a nucleic acid.
21. The method of any one claims 1-4, 7-15 or 17-20, the composition of any one of claims 5-14 or 20, or the use of any one of claims 16-18, wherein the antibody is provided as an antibody-drug conjugate.
Ref US18561018P: [content unavailable]