Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
1. Claims 1-65 are the original claims filed 3/8/2023. IN the Preliminary Amendment of 10/2/2023, claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-65 are amended, claims 4-11, 13-14, 16, 18- 19, 21-22, 24-25, 27-28, 30-32, 39-44 and 51-63 are canceled, and new claims 66-67 are added. In the Response of 4/13/2026, claims 1-3, 17, 20, 23, 26, 33-38, 45-46, and 66-67 are amended and claim 64 is canceled.
Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 65-67 are pending.
The Office Action is final.
Priority
2. USAN 18/025 203, filed 03/08/2023, is a National Stage entry of PCT/EP2021/075016, International Filing Date: 09/10/2021, PCT/EP2021/ 075016 Claims Priority from Provisional Application 63/076,797, filed 09/10/2020. The contents of the provisional application are similar to that of the instant application. The contents are hypothetical in both cases for the method dose regimen for treating DLBCL. Written description support and enablement for the claimed invention is provided in ClinicalTrials.gov ID NCT05578976 (GenMab; PTO 892).
Information Disclosure Statement
3. As of 5/6/2026, a total of seven (7) IDS are filed: 9/14/2023; 9/14/2023; 9/14/2023; 9/14/2023; 9/14/2023; 4/13/2026; and 4/13/2026. The corresponding initialed and dated 1449 form is considered and of record. The submissions are in compliance with the provisions of 37 CFR 1.97.
Withdrawal of Objections
Drawings
4. The objection to the drawing sheet for Figure 1 because of the improper use of the term “DuoBody”, which is a trade name or a mark used in commerce, is withdrawn. The replacement drawing sheet filed 4/13/2026 rectifies the deficiency.
Specification
5. The objection to the abstract of the disclosure because of indefinite language by use of parenthetical text and the term “e.g.,” is withdrawn. The parenthetical text is deleted in its entirety.
6. The objection to the disclosure because of informalities is withdrawn.
a) The specification is amended to rectify the improper use of the term DuoBody, GenBank, UniProt, Swiss-prot, Crossmab, Expi293, PER.C6, ALIGN, nanobody, which is a trade name or a mark used in commerce.
b) The specification is amended to include the full names for “R-CHOP” and “EPCO” used in the figure legend to Figure 2.
Claim Objections
7. The objection to Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 because of informalities is moot for the canceled claim(s) and withdrawn for the pending claims:
a) Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 are amended to recite “a 21-day cycle” throughout the claim set.
b) The objection to claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 for inconsistency in reciting “21-day” or “28-day” is withdrawn. Applicants explanation in the Response is appreciated.
c) Claim 1 is amended to correct a typographical error: “(e) vincristine is administered intravenously 2 once every 21-day cycle;”.
d) Claim 1 is amended to correct improper punctuation: “(a) epcoritamab or a biosimilar thereof, (b) rituximab,”.
e) Claim 1 is amended to correct improper punctuation: “wherein administration of the combination continues at least until the subject exhibits a complete metabolic response (CMR), a partial metabolic response, [or] a stable disease, [or] until progressive disease develops, or unacceptable toxicity occurs.”
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
8. The rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot for the canceled claim(s) and withdrawn for the pending claims.
Claim 1(a) is amended to delete element (iv) and to insert the “optional” clause reciting epcoritamab or the biosimilar thereof is administered in 28-day cycles, wherein epcoritamab or the biosimilar thereof is administered once every 28-day cycle.
Claim Rejections - 35 USC § 112(d)
9. The rejection of Claims 34, 36-37, 45-46 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends is withdrawn.
a) Claims 34(ii) and (iii), 36(ii) and (iii), and 37 (ii) and (iii) are amended to reciting “a full dose of 48 mg” (Claims 34 and 37) and “a full dose of 24 mg” (claim 36).
b) Claims 45-46 are amended to replace “the bispecific antibody” with “epcoritamab or the biosimilar thereof.”
Claim Rejections - 35 USC § 112(a)
Written Description
10. The rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 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 is moot for the canceled claim(s) and withdrawn for the pending claims.
The amendment of the claims to identify the structure of the epcoritamab biosimilar in combination with the final “wherein” clause with implied results from treating a subject having DLBLC are found to be persuasive in overcoming the rejection.
Enablement
11. The rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is moot for the canceled claim(s) and withdrawn for the pending claims.
The amendment of the claims to identify the structure of the epcoritamab biosimilar is found to be persuasive in overcoming the rejection.
Claim Rejections - 35 USC § 103
12. The rejection of Claim(s) 1 and 65 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) is withdrawn.
AS regards the Sureda reference and the comments applied to the publication date thereof, under MPEP 2143 “common knowledge” is available to support an obviousness rejection with a reasoned explanation why the invention is obvious.
AS regards Valbjoern (US 20220411505), Applicants proper statement of ownership disqualifies the commonly owned reference under 102(a)(2)(c).
Applicants aver on the record that after “extensive studies” the claimed methods are associated with “unexpected results.”
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13. The rejection of Claim(s) 2-3, 12, and 15 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
14. The rejection of Claim(s) 17, 20, 23, 26 and 29 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
15. The rejection of Claim(s) 33-34 and 36-37 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
16. The rejection of Claim(s) 45-46 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
17. The rejection of Claim(s) 47-50 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above, and further in view of Kramer (PTO 892) is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
18. The rejection of Claim(s) 64 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
19. The rejection of Claim(s) 1(iv), 35, 38 and 66-67 under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) as applied to claim 1 above is withdrawn.
See the Examiner’s comments set forth under section 12 herein above.
Double Patenting
20. The rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12435154 in view of Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) is moot for the canceled claim(s) and withdrawn for the pending claims.
Claims 1-29 of U.S. Patent No. 12435154 do not encompass R-CHOP nor does the specification provide adequate support for the instant claimed method combination with dosage regimen.
See the Examiner’s comments set forth under section 12 herein above.
21. The provisional rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 69, 70, 72-89 and 98-108 of copending Application No. 17/ 923,317 (US 20230227570) in view of in view of Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) is moot for the canceled claim(s) and withdrawn for the pending claims.
Claims 69, 70, 72-89 and 98-108 of copending Application No. 17/ 923,317 do not encompass R-CHOP nor does the specification provide adequate support for the instant claimed method combination with dosage regimen.
See the Examiner’s comments set forth under section 12 herein above.
Rejections Maintained
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.
22. The rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 65-67 on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11845805
The references Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) fall from the rejection for the reasons discussed under section 12 hereinabove.
The rejection is maintained for ref claims 1-33 of U.S. Patent No. 11845805 as set forth below from the original rejection. Applicants make no assertion on p. 34 of the Response that the ref patent claims are patentably distinct from the instant claims.
Ref claims
1. A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject a bispecific antibody, and an effective amount of (a) rituximab, (b) cyclophosphamide, (c) doxorubicin, (d) vincristine and (e) prednisone, wherein the bispecific antibody comprises: (i) a first binding arm comprising a first antigen-binding region which binds to human CD3c (epsilon) and comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the CDR1, CDR2 and CDR3 sequences that are in the VH sequence of SEQ ID NO: 6, and the VL comprises the CDR1, CDR2 and CDR3 sequences that are in the VL sequence of SEQ ID NO: 7; and (ii) a second binding arm comprising a second antigen-binding region which binds to human CD20 and comprises a VH and a VL, wherein the VH comprises the CDR1, CDR2 and CDR3 sequences that are in the VH sequence of SEQ ID NO: 13, and the VL comprises the CDR1, CDR2 and CDR3 sequences that are in the VL sequence of SEQ ID NO: 14; wherein rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and the bispecific antibody are administered in 21-day cycles; and wherein (a) a priming dose of the bispecific antibody is administered on day 1 of cycle 1 of the 21-day cycles, an intermediate dose of the bispecific antibody is administered on day 8 of cycle 1 of the 21-day cycles, a dose of 24 mg or 48 mg of the bispecific antibody is administered on day 15 of cycle 1 of the 21-day cycles, and a dose of 24 or 48 mg of the bispecific antibody is administered weekly starting on day 1 of cycle 2 of the 21-day cycles; (b) rituximab is administered once every three weeks for six or eight 21-day cycles, and (c) cyclophosphamide is administered once every three weeks for six or eight 21-day cycles, and (d) doxorubicin is administered once every three weeks for six or eight 21-day cycles, and (e) vincristine is administered once every three weeks for six or eight 21-day cycles, and (f) prednisone is administered once a day from day 1 to day 5 of each 21-day cycles for six or eight 21-day cycles.
2. The method of claim 1, wherein the bispecific antibody is administered at a weekly dose of 24 mg starting on day 1 of cycle 2 of the 21-day cycles.
3. The method of claim 1, wherein the bispecific antibody is administered at a weekly dose of 48 mg starting on day 1 of cycle 2 of the 21-day cycles.
4. The method of claim 1, wherein the weekly administration of 24 mg or 48 mg of the bispecific antibody is performed for three and one-third 21-day cycles.
5. The method of claim 4, wherein after the weekly administration of the bispecific antibody for three and one-third 21-day cycles, the bispecific antibody is administered once every three weeks for two or four 21-day cycles.
6. The method of claim 5, wherein after the administration of the bispecific antibody once every three weeks for two or four 21-day cycles, the bispecific antibody is administered once every four weeks in 28-day cycles for up to one year total duration of treatment with the bispecific antibody.
7. The method of claim 1, wherein (a) the priming dose of the bispecific antibody is 0.16 mg, (b) intermediate dose of the bispecific antibody is 0.8 mg, or (c) the priming dose of the bispecific antibody is 0.16 mg and the intermediate dose of the bispecific antibody is 0.8 mg.
8. The method of claim 1, wherein rituximab is administered at a dose of 375 mg/m.sup.2, cyclophosphamide is administered at a dose of 750 mg/m.sup.2, doxorubicin is administered at a dose of 50 mg/m.sup.2, vincristine is administered at a dose of 1.4 mg/m.sup.2, and prednisone is administered at a dose of 100 mg/day.
9. The method of claim 1, wherein: (a) the bispecific antibody is administered as follows: (i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg or 48 mg is administered on day 15; (ii) in cycles 2-4, a dose of 24 mg or 48 mg is administered on days 1, 8, and 15; (iii) in cycles 5 and 6, a dose of 24 mg or 48 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-6; and (c) prednisone is administered on days 1-5 in cycles 1-6.
10. The method of claim 9, wherein the bispecific antibody is administered once every four weeks in 28-day cycles on day 1 from cycle 7.
11. The method of claim 1, wherein: (a) the bispecific antibody is administered as follows: (i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg or 48 mg is administered on day 15; (ii) in cycles 2-4, a dose of 24 mg or 48 mg is administered on days 1, 8, and 15; (iii) in cycles 5-8, a dose of 24 mg or 48 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-8; and (c) prednisone is administered on days 1-5 in cycles 1-8.
12. The method of claim 11, wherein the bispecific antibody is administered once every four weeks in 28-day cycles on day 1 from cycle 9.
13. The method of claim 1, wherein the bispecific antibody is administered subcutaneously.
14. The method of claim 1, wherein rituximab is administered intravenously, wherein cyclophosphamide is administered intravenously, wherein doxorubicin is administered intravenously, wherein vincristine is administered intravenously and wherein prednisone is administered intravenously or orally.
15. The method of claim 1, wherein (a) the DLBCL is double-hit or triple-hit DLBCL, and/or (b) the DLBCL is follicular lymphoma Grade 3B, and/or (c) the subject has an International Prognostic Index (IPI) score or Revised-IPI score>3, and/or (d) the subject has not received prior therapy for DLBCL or follicular lymphoma Grade 3B.
16. The method of claim 1, wherein: (i) the VH and VL of the first antigen-binding region of the bispecific antibody comprise the amino acid sequence of SEQ ID NO: 6 and SEQ ID NO: 7, respectively; and (ii) the VH and VL of the second antigen-binding region of the bispecific antibody comprise the amino acid sequence of SEQ ID NO: 13 and SEQ ID NO: 14, respectively.
17. The method of claim 1, wherein the first binding arm of the bispecific antibody is derived from a humanized antibody and comprises a λ light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 22 and/or the second binding arm of the bispecific antibody is derived from a human antibody and comprises a κ light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 23.
18. The method of claim 1, wherein the bispecific antibody is a full-length antibody with a human IgG1 constant region.
19. The method of claim 1, wherein the bispecific antibody comprises an inert Fc region.
20. The method of claim 1, wherein the bispecific antibody comprises a first heavy chain and a second heavy chain, wherein (i) in both the first and second heavy chains, the amino acids in the positions corresponding to positions L234, L235, and D265 in the human IgG1 heavy chain constant region of SEQ ID NO: 15 are F, E, and A, respectively, and (ii) in the first heavy chain, the amino acid in the position corresponding to F405 in the human IgG1 heavy chain constant region of SEQ ID NO: 15 is L, and wherein in the second heavy chain, the amino acid in the position corresponding to K409 in the human IgG1 heavy chain constant region of SEQ ID NO: 15 is R, or vice versa.
21. The method of claim 1, wherein the bispecific antibody comprises heavy chain constant regions comprising the amino acid sequences of SEQ ID NOs: 19 and 20.
22. The method of claim 1, wherein the bispecific antibody comprises a first heavy chain and a first light chain comprising the amino acid sequences set forth in SEQ ID NOs: 24 and 25, respectively, and a second heavy chain and a second light chain comprising the amino acid sequences set forth in SEQ ID NOs: 26 and 27, respectively.
23. The method of claim 1, wherein the bispecific antibody is epcoritamab, or a biosimilar thereof.
24. A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject a bispecific antibody, and an effective amount of (a) rituximab, (b) cyclophosphamide, (c) doxorubicin, (d) vincristine and (e) prednisone, wherein the bispecific antibody comprises a first heavy chain and a first light chain comprising the amino acid sequences set forth in SEQ ID NOs: 24 and 25, respectively, and a second heavy chain and a second light chain comprising the amino acid sequences set forth in SEQ ID NOs: 26 and 27, respectively, and wherein rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and the bispecific antibody are administered in 21-day cycles, wherein: (a) the bispecific antibody is administered as follows: (i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg or 48 mg is administered on day 15; (ii) in cycles 2-4, a dose of 24 mg or 48 mg is administered on days 1, 8, and 15; (iii) in cycles 5 and 6, a dose of 24 mg or 48 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-6; and (c) prednisone is administered on days 1-5 in cycles 1-6.
25. The method of claim 24, wherein the bispecific antibody is administered once every four weeks in 28-day cycles on day 1 from cycle 7.
26. A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject a bispecific antibody, and an effective amount of (a) rituximab, (b) cyclophosphamide, (c) doxorubicin, (d) vincristine and (e) prednisone, wherein the bispecific antibody comprises a first heavy chain and a first light chain comprising the amino acid sequences set forth in SEQ ID NOs: 24 and 25, respectively, and a second heavy chain and a second light chain comprising the amino acid sequences set forth in SEQ ID NOs: 26 and 27, respectively, and wherein rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and the bispecific antibody are administered in 21-day cycles, wherein: (a) the bispecific antibody is administered as follows: (i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg or 48 mg is administered on day 15; (ii) in cycles 2-4, a dose of 24 mg or 48 mg is administered on days 1, 8, and 15; (iii) in cycles 5-8, a dose of 24 mg or 48 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-8; and (c) prednisone is administered on days 1-5 in cycles 1-8.
27. The method of claim 26, wherein the bispecific antibody is administered once every four weeks in 28-day cycles on day 1 from cycle 9.
28. The method of claim 1, wherein administration of (a) rituximab, (b) cyclophosphamide, (c) doxorubicin, (d) vincristine and (e) prednisone in 21-day cycles continues at least until the subject exhibits a complete metabolic response (CMR), or a partial metabolic response.
29. A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject a combination of epcoritamab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, wherein the combination is administered in 21-day cycles; and wherein (a) a priming dose of epcoritamab is administered subcutaneously on day 1 of cycle 1 of the 21-day cycles, an intermediate dose of epcoritamab is administered subcutaneously on day 8 of cycle 1 of the 21-day cycles, a full dose of 24 mg or 48 mg of epcoritamab is subcutaneously administered on day 15 of cycle 1 of the 21-day cycles, and a full dose of 24 or 48 mg of the epcoritamab is administered subcutaneously weekly starting on day 1 of cycle 2 of the 21-day cycles, wherein the priming dose and intermediate dose are at a lower dose as compared with the full dose; (b) rituximab is administered intravenously at a dose of 375 mg/m.sup.2 once every three weeks for six or eight 21-day cycles; (c) cyclophosphamide is administered intravenously at a dose of 750 mg/m.sup.2 once every three weeks for six or eight 21-day cycles; (d) doxorubicin is administered intravenously at a dose of 50 mg/m.sup.2 once every three weeks for six or eight 21-day cycles; (e) vincristine is administered intravenously at a dose of 1.4 mg/m.sup.2 once every three weeks for six or eight 21-day cycles; and (f) prednisone is administered intravenously or orally at a dose of 100 mg/day once a day from day 1 to day 5 of each 21-day cycles for six or eight 21-day cycles; wherein administration of the combination in 21-day cycles continues at least until the subject exhibits a complete metabolic response (CMR), or a partial metabolic response.
30. The method of claim 29, wherein the epcoritamab is administered at a full dose of 24 mg.
31. The method of claim 29, wherein the epcoritamab is administered at a full dose of 48 mg.
32. The method of claim 29, wherein the priming dose of epcoritamab is 0.16 mg.
33. The method of claim 29, wherein the intermediate dose of epcoritamab is 0.8 mg.
The rejection is maintained.
23. The provisional rejection of Claims 1-3, 12, 15, 17, 20, 23, 26, 29, 33-38, 45-50, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 12, 15, 17, 20, 23, 26, 29, 33-38, 46-50, 64-67 of copending Application No. 18/500,799 (US 20240301078)
The references Van Den Brink et al. (US 20160333095) in view of Valbjoern (US 20220411505; 8/19/2020) and Mounier et al. (Blood, 2003, 101: 4279-4284, IDS 9/14/2023) as evidenced by Sureda (EMJ Oncol. 2021; 9 [Suppl 8]:2-12 with reference to PeerVoice (20th May 2021)) fall from the rejection for the reasons discussed under section 12 hereinabove.
The rejection is maintained for ref claims 1-8, 12, 15, 17, 20, 23, 26, 29, 33-38, 46-50, 64-67 of copending Application No. 18/500,799 as set forth below from the original rejection. Applicants make no assertion on p. 34 of the Response that the ref claims are patentably distinct from the instant claims.
Ref claims
1. (Currently Amended) A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject a bispecific antibody, and an effective amount of a combination of (a) epcoritamab or a biosimilar thereof (ab) rituximab, (bc) cyclophosphamide, (ed) doxorubicin, (de) vincristine and (ef) prednisone, in 21-day cycles, wherein (a) epcoritamab or a biosimilar thereof is administered subcutaneously, wherein (i) a priming dose is administered on day 1 of the first 21-day cycle, an intermediate dose is administered on day 8 of the first 21-day cycle, and a full dose of 24 or 48 mg on day 15 of the first 21-day cycle, wherein the priming dose and intermediate dose are at a lower dose as compared with the full dose,(ii) a full dose of 24 or 48 mg on days 1, 8 and 15 of the second, third and fourth 21- day cycles;(iii) a full dose of 24 or 48 mg is administered once every three weeks on day 1 of two to four subsequent 21-day cycles; and(iv) a full dose of 24 or 48 mg is subsequently administered one every four weeks on day 1 in 28-day cycles;(b) rituximab is administered intravenously at a dose of 375 mg/m2 once every three weeks;(c) cyclophosphamide is administered intravenously at a dose of 750 mg/m2 once every three weeks;(d) doxorubicin is administered intravenously at a dose of 50 mgz/m2 once every three weeks;(e) vincristine is administered intravenously weeks at a dose of 1.4 mg/m2 once every three ;and (f) prednisone is administered orally or intravenously at a dose of 100 mg once a day from day 1 to day 5 of each 21 day cycle;wherein administration of the combination continues at least until the subject exhibits a complete metabolic response (CMR), a partial metabolic response or stable disease, or until progressive disease develops or unacceptable toxicity occurswherein the a bispecific antibody comprises:(i) a first binding arm comprising a first antigen-binding region which binds to human CD3c (epsilon) and comprises a variable heavy chain (VH) region and a variable light chain (VL) region, wherein the VH region comprises the CDR1, CDR2 and CDR3 sequences that are in the VH region sequence of SEQ ID NO: 6, and the VL region comprises the CDR1, CDR2 and CDR3 sequences that are in the VL region sequence of SEQ ID NO: 7; and(ii) a second binding arm comprising a second antigen-binding region which binds to human CD20 and comprises a VH region and a VL region, wherein the VH region comprises the CDR1, CDR2 and CDR3 sequences that are in the VH region sequence of SEQ ID NO: 13, and the VL region comprises the CDR1, CDR2 and CDR3 sequences that are in the VL region sequence of SEQ ID NO: 14;wherein the bispecific antibody is administered at a dose of 24 mg or 48 mg, and wherein rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and the bispecific antibody are administered in 21-day cycles.
2. (Currently Amended) The method of claim 1, wherein epcoritamab or a biosimilar thereof the bispecific antibody is administered at a full dose of 24 mg.
3. (Currently Amended) The method of claim 1, wherein epcoritamab or a biosimilar thereof the bispecific antibody is administered at a full dose of 48 mg.
4-11. (Canceled)
12. (Currently Amended) The method of claim 10 or 11 claim 1,wherein the priming dose is 0.16 mg.
13-14. (Canceled)
15. (Currently Amended) The method of claim 13 or 14claim1,wherein the intermediate dose is 0.8 mg.
16. (Canceled)
17. (Currently Amended) The method of claim 16claim1,wherein the administration of rituximab once every three weeks is performed for six or eight 21-day cycles.
18-19. (Canceled)
20. (Currently Amended) The method of claim 19claim1,wherein the administration of cyclophosphamide once every three weeks is performed for six or eight 21-day cycles.
21-22. (Canceled)
23. (Currently Amended) The method of claim 22claim1,wherein the administration of doxorubicin once every three weeks is performed for six or eight 21-day cycles.
24-25. (Canceled)
26. (Currently Amended) The method of claim 25claim1,wherein the administration of vincristine once every three weeks is performed for six or eight 21-day cycles.
27-28. (Canceled)
29. (Currently Amended) The method of claim 28claim1,wherein prednisone is administered for six or eight 21-day cycles.
30-32. (Canceled)
33. (Currently Amended) The method of any one of claimsclaim 1, 2, and 4-32, wherein administration is performed in 21-day cycles, and wherein:(a) the bispecific antibody epcoritamab or a biosimilar thereof is administered as follows:(i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg is administered on day 15; (ii) in cycles 2-4, a full dose of 24 mg is administered on days 1, 8, and 15; (iii) in cycles 5 and 6, a fulldose of 24 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-6; and (c) prednisone is administered on days 1-5 in cycles 1-6.
34. (Currently Amended) The method of any one of claimsclaim 12 and 3-32, wherein administration is performed in 21-day cycles, and wherein:(a) the bispecific antibody epcoritamab or a biosimilar thereof is administered as follows:(i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 48 mg is administered on day 15; (ii) in cycles 2-4, a dose of 48 mg is administered on days 1, 8, and 15; (iii) in cycles 5 and 6, a dose of 48 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-6; and (c) prednisone is administered on days 1-5 in cycles 1-6.
35. (Currently Amended) The method of claim 332or 34 wherein the bispecific antibody epcoritamab or a biosimilar thereof is administered once every four weeks in 28-day cycles on day 1 from cycle 7.
36. (Currently Amended) The method of any one of claimsclaim 1, 2, and 4-32, wherein administration is performed in 21-day cycles, and wherein:(a) the bispecific antibody epcoritamab or a biosimilar thereof is administered as follows:(i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg is administered on day 15; (ii) in cycles 2-4, a dose of 24 mg is administered on days 1, 8, and 15; (iii) in cycles 5-8, a dose of 24 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-8; and (c) prednisone is administered on days 1-5 in cycles 1-8.
37. (Currently Amended) The method of any one of claims claim 1 and 3-32, wherein administration is performed in 21-day cycles, and wherein:(a) the bispecific antibody epcoritamab or a biosimilar thereof is administered as follows:(i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 48 mg is administered on day 15; (ii) in cycles 2-4, a dose of 48 mg is administered on days 1, 8, and 15; (iii) in cycles 5-8, a dose of 48 mg is administered on day 1; (b) rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on day 1 in cycles 1-8; and (c) prednisone is administered on days 1-5 in cycles 1-8.
38. (Currently Amended) The method of claim 36 or 37,wherein the bispecific antibodyepcoritamab or a biosimilar thereof is administered once every four weeks in 28-day cycles on day 1 from cycle 9.
39-44. (Canceled)
45. (Currently Amended) The method of any one of claims 1-44claim1,wherein rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and the bispecific antibody are administered sequentially.
46. (Currently Amended) The method of any one of claims 1-45claim1,wherein prednisone is administered first, rituximab is administered second, cyclophosphamide is administered third, doxorubicin is administered fourth, vincristine is administered fifth, and the bispecific antibody epcoritamab or a biosimilar thereof is administered last if rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and the bispecific antibody are administered on the same day.
47. (Currently Amended) The method of any one of claims 1-46claim1,wherein the DLBCL is double-hit or triple-hit DLBCL.
48. (Currently Amended) The method of any one of claims 1-47claim1,wherein the DLBCL is follicular lymphoma Grade 3B.
49. (Currently Amended) The method of any one of claims 1-48claim1,wherein the subject has an International Prognostic Index (IPI) score or Revised-IPI score >3.
50. (Currently Amended) The method of any one of claims 1-49claim1,wherein the subject has not received prior therapy for DLBCL or follicular lymphoma Grade 3B.
51-63. (Canceled)
64. (Currently Amended) The method of any one of claims 1-63claim1,wherein the bispecific antibody comprises method comprises administering a biosimilar of epcoritamab comprising a heavy chain and a light chain consisting of the amino acid sequence of SEQ ID NOs: 24 and 25, respectively, and a heavy chain and a light chain consisting of the amino acid sequence of SEQ ID NOs: 26 and 27, respectively.
65. (Currently Amended) The method of any one of claims 1-64claim1,wherein the bispecific antibody is method comprises administration of epcoritamab, or a biosimilar thereof.
66. (New) The method of claim 34, wherein epcoritamab or a biosimilar thereof is administered once every four weeks in 28-day cycles on day 1 from cycle 7.
67. (New) The method of claim 37, wherein epcoritamab or a biosimilar thereof is administered once every four weeks in 28-day cycles on day 1 from cycle 9.
This is a provisional nonstatutory double patenting rejection.
Conclusion
24. No claims are allowed.
25. 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.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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