DETAILED ACTION
Claims 1-20 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 06/04/2023 has been considered by the examiner.
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 1-14, 16-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Gardai et al., (US11213584B2) (effectively filed on 10/29/2015), in view of Oliva et al. “Uveal melanoma as a target for immune-therapy.” Annals of translational medicine vol. 4,9 (2016): 172. doi:10.21037/atm.2016.05.04.
Gardai teaches a method of treating melanoma, comprising administering a composition comprising an anti-CD40 antibody to a patient with melanoma, wherein the anti-CD40 antibody comprises: 1) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 1; 2) a light chain variable region comprising an amino acid sequence of SEQ ID NO:2; and 3) a human constant region; wherein the human constant region comprises an N-glycoside-linked sugar chain at residue N297 (EU numbering), wherein less than 5% of N-glycoside-linked sugar chains at residue N297 (EU numbering) in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level of about 3 µg/kg, about 10 µg/kg, about 30 µg/kg, about 45 µg/kg (µg antibody per kilogram patient body weight) (see claims 1-2 of ‘358, See claim 15 of ‘358 teaching the cancer being melanoma) (instant claims 1-2 and 19). Gardai teaches the anti-CD40 antibody being administered every three weeks or six weeks, further administering a chemotherapeutic agent, where the chemotherapeutic agent is gemcitabine and/or paclitaxel (see claims 9-10 and 31 of ‘358, see column 2 teaching administration every six weeks) (instant claims 3-5 and 10-12).
Gardai further teaches a method of treating melanoma, comprising administering 1) a composition comprising an anti-CD40 antibody; and 2) an anti-PD 1 antibody or an anti-PDL1 antibody to a patient with melanoma, wherein the anti-CD40 antibody comprises: 1) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 1; 2) a light chain variable region comprising an amino acid sequence of SEQ ID NO:2; and 3) a human constant region; wherein the human constant region comprises an N-glycoside-linked sugar chain at residue N297 (EU numbering), wherein less than 5% of the N-glycoside-linked sugar chains at residue N297 (EU numbering) in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level of about 3 µg/kg, about 10 µg/kg, about 30 µg/kg, about 45 µg/kg (µg antibody per kilogram patient body weight) (See claim 2 of ‘358, See claim 15 of ‘358 teaching the cancer being melanoma) (instant claims 6, 9, 13, and 20). Gardai teaches the anti-PD1 antibodies are pembrolizumab, nivolumab, MEDI4736, MPDL3280A (see columns 2-3 teaching pembrolizumab, nivolumab, MEDI4736, MPDL3280A), MEDI0680, pidilizumab, AMP-224 (see column 15 lines 53-65 teaching MEDI0680, pidilizumab, AMP-224), atezolizumab, durvalumab (see claim 2 of ‘358 teaching atezolizumab and durvalumab), BMS-936559/MDX-1105 and MSB0010718C (see column 16 teaching BMS-936559/MDX-1105 and MSB0010718C) (instant claims 7-8 and 14). Gardai teaches the anti-CD40 antibody being administered intravenously or subcutaneously to the patient and/or the anti-PDL1 antibody is administered intravenously or subcutaneously to the patient (see claim 33 of ‘358 and column 6 lines 55-63 teaching administration methods) (instant claims 16-17).
Gardai does not teach the melanoma being uveal.
Oliva teaches the most common primary intraocular malignant tumor in adults (see page 1). Oliva further teaches a loss of certain markers expressed in eye tissues and TAM’s, like CD40, a marker necessary for lymphocyte T-mediated immune-response has been observed with uveal melanoma (see page 4). Lastly, Oliva teaches PD-1 and PD-L1 antibodies have been shown impressive activity in metastatic melanoma (see page 2, see page 5).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the methods of treating melanoma with CD-40, PD-L, and PD-L1 antibodies of Gardai with Oliva’s teaching of CD-40, PD-L, and PD-L1 being associated with uveal melanoma. Oliva provides motivation by teaching that tumor-associated macrophages (TAMs), like CD-40, are responsible immune-suppression (see page 4). Oliva teaches that M2 TAMS can modify T-lymphocyte responses as they drive the conversion a naïve T-cells to T-regulatory lymphocytes (T-reg) and regulate their recruitment (see page 4). Oliva teaches that antibodies against T-cell programmed death-1 (PD-1) checkpoint protein have shown impressive activity in metastatic melanoma (see page 2). Oliva further teaches the most relevant mechanism to inhibit T-cell action by tumor cells is the overexpression of PD-L1 receptor, and the same can be said for uveal melanoma (see page 5). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over claims Gardai and Oliva et al., as applied to claims 1-14, 16-17, and 19-20 above, and in view of Rangwala et al., (WO 2019217457A1) (effectively filed on 05/07/2019).
The teachings of Gardai and Oliva as they pertain to claims 1-14, 16-17, and 19-20 are discussed in the 35 USC 103 rejection above.
Gardai teaches administering anti-CD40 antibodies on day one of a three-week cycle (see claim 32 of ‘358) (instant claim 18). Gardai does not teach administering anti-PD 1 antibodies on day two of a three-week cycle.
Rangwala teaches anti-PD-1 antibodies being administered on a three-week cycle (see [0186], see [0189]). Rangwala does no teach administering anti-PD-1 antibodies on day two of a three-week cycle. However, it would have been obvious to one of ordinary skill in the art to perform routine optimization of determining the days that anti-PD-1 antibodies would be administered within that three-week cycle.
It would have been obvious at the time of the instant application to combine the methods of treating melanoma with CD-40, PD-L, and PD-L1 antibodies of Gardai with Oliva’s teaching of CD-40, PD-L, and PD-L1 being associated with uveal melanoma, with Rangwala’s teachings of administering anti-PD-1 antibodies on a three-week cycle in order to treat a subject with cancer. Rangwala provides motivation by teaching that anti-PD-1 antibodies inhibit PD-1 activity (see [0123]) and PD-1 is expressed predominantly on previously activated T-cells in vivo, and binds to two ligands PD-L1 and PD-L2 (see [0046]). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
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 1-6, 8-13, 16-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 9-10, 15, 29-30, 33, 42, and 44 of U.S. Patent No. 11213584, in view of Oliva et al. “Uveal melanoma as a target for immune-therapy.” Annals of translational medicine vol. 4,9 (2016): 172. doi:10.21037/atm.2016.05.04. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘584 teaches a method of treating melanoma, comprising administering a composition comprising an anti-CD40 antibody to a patient with uveal melanoma, wherein the anti-CD40 antibody comprises: 1) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 1; 2) a light chain variable region comprising an amino acid sequence of SEQ ID NO:2; and 3) a human constant region; wherein the human constant region comprises an N-glycoside-linked sugar chain at residue N297 (EU numbering), wherein less than 5% of N-glycoside-linked sugar chains at residue N297 (EU numbering) in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level of about 3 µg/kg, about 10 µg/kg, about 30 µg/kg, about 45 µg/kg, or about 60 µg/kg (µg antibody per kilogram patient body weight}.
Regarding instant claim 1, ‘584 teaches a method of treating melanoma, comprising administering a composition comprising an anti-CD40 antibody to a patient with uveal melanoma, wherein the anti-CD40 antibody comprises: 1) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 1; 2) a light chain variable region comprising an amino acid sequence of SEQ ID NO:2; and 3) a human constant region; wherein the human constant region comprises an N-glycoside-linked sugar chain at residue N297 (EU numbering), wherein less than 5% of N-glycoside-linked sugar chains at residue N297 (EU numbering) in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level of about 3 µg/kg, about 10 µg/kg, about 30 µg/kg, about 45 µg/kg, or about 60 µg/kg (µg antibody per kilogram patient body weight} (claim 2 of ‘584). ‘548 does not teach the melanoma being uveal melanoma.
Oliva teaches the most common primary intraocular malignant tumor in adults (see page 1). Oliva further teaches a loss of certain markers expressed in eye tissues and TAM’s, like CD40, a marker necessary for lymphocyte T-mediated immune-response has been observed with uveal melanoma (see page 4). Lastly, Oliva teaches PD-1 and PD-L1 antibodies have been shown impressive activity in metastatic melanoma (see page 2, see page 5).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the methods of treating melanoma with CD-40, PD-L, and PD-L1 antibodies of ‘548 with Oliva’s teaching of CD-40, PD-L, and PD-L1 being associated with uveal melanoma. Oliva provides motivation by teaching that tumor-associated macrophages (TAMs), like CD-40, are responsible immune-suppression (see page 4). Oliva teaches that M2 TAMS can modify T-lymphocyte responses as they drive the conversion a naïve T-cells to T-regulatory lymphocytes (T-reg) and regulate their recruitment (see page 4). Oliva teaches that antibodies against T-cell programmed death-1 (PD-1) checkpoint protein have shown impressive activity in metastatic melanoma (see page 2). Oliva further teaches the most relevant mechanism to inhibit T-cell action by tumor cells is the overexpression of PD-L1 receptor, and the same can be said for uveal melanoma (see page 5). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
Regarding instant claims 2 and 9, ‘584 teaches wherein the dose level is about 30 µg/kg (see claim 2 of ‘584).
Regarding instant claims 3 and 10, ‘584 teaches wherein the anti-CD40 antibody is administered every three weeks or every six weeks (see claim 42 of ‘584).
Regarding instant claims 4-5 and 11-12, ‘584 teaches administering a chemotherapeutic agent, wherein the chemotherapeutic agent is gemcitabine and/or paclitaxel (see claims 9-10 of ‘584).
Regarding instant claim 6, ‘584 teaches a method of treating melanoma, comprising administering 1) a composition comprising an anti-CD40 antibody; and 2) an anti-PD 1 antibody or an anti-PDL1 antibody to a patient with uveal melanoma, wherein the anti-CD40 antibody comprises: 1) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 1; 2) a light chain variable region comprising an amino acid sequence of SEQ ID NO:2; and 3) a human constant region; wherein the human constant region comprises an N-glycoside-linked sugar chain at residue N297 (EU numbering), wherein less than 5% of the N-glycoside-linked sugar chains at residue N297 (EU numbering) in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level of about 3 µg/kg, about 10 µg/kg, about 30 µg/kg, about 45 µg/kg, or about 60 µg/kg (µg antibody per kilogram patient body weight} (see claim 2 and 15 of ‘584). ‘584 does not teach the melanoma being uveal melanoma.
Oliva teaches the most common primary intraocular malignant tumor in adults (see page 1). Oliva further teaches a loss of certain markers expressed in eye tissues and TAM’s, like CD40, a marker necessary for lymphocyte T-mediated immune-response has been observed with uveal melanoma (see page 4). Lastly, Oliva teaches PD-1 and PD-L1 antibodies have been shown impressive activity in metastatic melanoma (see page 2, see page 5).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the methods of treating melanoma with CD-40, PD-L, and PD-L1 antibodies of ‘548 with Oliva’s teaching of CD-40, PD-L, and PD-L1 being associated with uveal melanoma. Oliva provides motivation by teaching that tumor-associated macrophages (TAMs), like CD-40, are responsible immune-suppression (see page 4). Oliva teaches that M2 TAMS can modify T-lymphocyte responses as they drive the conversion a naïve T-cells to T-regulatory lymphocytes (T-reg) and regulate their recruitment (see page 4). Oliva teaches that antibodies against T-cell programmed death-1 (PD-1) checkpoint protein have shown impressive activity in metastatic melanoma (see page 2). Oliva further teaches the most relevant mechanism to inhibit T-cell action by tumor cells is the overexpression of PD-L1 receptor, and the same can be said for uveal melanoma (see page 5). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
Regarding instant claim 8, ‘584 teaches wherein the anti-PD1 antibody is selected from the group consisting of atezolizumab, durvalumab, avelumab, SHR-1316, MEDI4736, BMS-936559/MDX-1105, MSB0010718C, MPDL3280A, and envafolimab (see claim 2 of ‘584).
Regarding instant claim 13, ‘584 teaches administering 1) an anti-CD40 antibody and 2) an anti-PD 1 antibody (see claim 2 of ‘584).
Regarding instant claims 16-17, ‘584 teaches wherein the anti-CD40 antibody is administered intravenously or subcutaneously to the patient (see claims 33 and 44 of ‘584).
Regarding instant claims 19-20, ‘584 teaches wherein the dose level is about 10 µg/kg (see claims 29-30 of ‘584).
This is a nonstatutory double patenting rejection.
Allowable Subject Matter
Claim 15 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678