DETAILED ACTION
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 .
Claim Status
Claims 1-100 are cancelled. Claims 101-118 as filed on 07 April 2025 are pending and under examination.
Claim Rejections - 35 USC § 103
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 101-118 are rejected under 35 U.S.C. 103 as being unpatentable over Adams (WO 2021/228783 A1) (IDS 06/20/2025 FOR # 2).
Regarding claims 101-102, 104, 106-108, and 113-115, Adams teaches a method of treating cancer including multiple myeloma using BCMAxCD3 bispecific antibody where the bispecific antibody is teclistamab (abstract, page 4 in lines 26, and Figure 1). Adams teaches SEQ ID NO: 10 which matches instant SEQ ID NO: 10, SEQ ID NO: 11 which matches instant SEQ ID NO: 11, SEQ ID NO: 20 which matches instant SEQ ID NO: 20, and SEQ ID NO: 21 which matches instant SEQ ID NO: 21 (page 4 in lines 22-25). These sequences teach the CDRs of claim 101 and the VH and VL sequences of claim 102. Adams teaches the method comprises the administration of one or more step-up or priming doses of the bispecific antibody prior to administering the first treatment dose of the bispecific (page 25 in lines 25-33) as required by claims 106 and 113. Adams further teaches the administration of a first dose repeated once a week for any interval from one week to three months, a second dose administered every two weeks for an additional number of weeks, then a third dose administered every week for an additional number of weeks (page 24 in lines 12-21) which would include a duration of 28 days as required by claim 101. Admas teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg (page 26 in lines 28-33 and page 27 in lines 1-6). These potential dosing schedules and amounts would include the weekly treatment at about 1500 µg/kg and bi-weekly dose of about 3000 µg/kg required by claims 107 and 114; the weekly dose of about 1500 µg/kg, the bi-weekly dose of about 3000 µg/kg, and once monthly dose of about 3000 µg/kg of claims 108 and 115.
Regarding claim 103, Adams teaches SEQ ID NO: 12 which matches instant SEQ ID NO: 12, SEQ ID NO: 13 which matches instant SEQ ID NO: 13, SEQ ID NO: 22 which matches instant SEQ ID NO: 22, and SEQ ID NO: 23 which matches instant SEQ ID NO: 23 (page 16 in lines 32-33 and page 17 in lines 1-2).
Regarding claims 105 and 112, Adams teaches the treatment of relapsed or refractory multiple myeloma (page 19 in lines 29-33).
Regarding claims 109 and 116, Adams teaches the subject being treated attains a stringent complete response according (page 4 in lines 11-16) and teaches the IMWG diagnostic criteria for multiple myeloma for use in assessing patients (page 44 in line 11).
Regarding claims 110 and 117, Adams teaches the combination with daratumumab (Example 4).
Regarding claims 111 and 118, Adams teaches 1-3 step-doses where the step-up doses for subcutaneous administration are 0.08 mg/kg, 2.4 mg/kg, and 7.2 mg/kg (Figure 9) but further teaches step-up or priming doses can be 0.0001 mg/kg to about 5 mg/kg (page 26 in lines 25-33). Adams teaches the step-up doses occurring in a single week (Figure 9) and further teaches 2 or 3 day intervals between the subcutaneous step-up doses. Teaching the step-up doses of claims 111 and 118. Adams teaches the subcutaneous administration of 1.5 mg/kg for the first dose and a second dose of 3 mg/kg (Figure 9), and teaches maintenance doses of a range of doses including 3 mg/kg (page 24 in lines 22-32). These maintenance doses are taught as administered weekly (page 24 in lines 22-23). Admas teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg (page 26 in lines 28-33 and page 27 in lines 1-6).
Adams teaches a method of treating multiple myeloma with the administration of the bispecific antibody teclistamab with step-up doses, three dose levels with varying administration intervals. Adams teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg and a first dose every week, a second dose bi-weekly, and a third dose administered weekly. Adams teaches the first, second, and third administration schedules can have a duration of one to three months which would include 28 days.
Adams teaches a therapeutically effective dose varies based on the therapeutic and patient population (page 13 in lines 15-51) and further teaches the use of Phase 1 and 2 clinical trials for determining safety and effectiveness of a therapeutic, and optimization of dose amount and schedule (Example 3).
Adams does not teach a third or maintenance dose administered monthly.
It would have been obvious at the time the application was filed to optimize the 3rd dose or maintenance dose administered weekly to a monthly administration using known in the art routine experimentation to arrive at a method of treatment where teclistamab is administered at three step-up doses, a first dose administered weekly at 1.5m/kg for 28 days, a second dose administered biweekly at 3 mg/kg, and a third dose of 3 mg/kg administered monthly instead of weekly administration for the third dose as taught by Adams. One of skill in the art would have been motivated to optimize the teachings of Adams to determine the most effective dosing using the clinical trial method well known in the art and taught by Adams. There would have been a reasonable expectation of success as clinical trials are routine experimentation in antibodies used in a method of treating cancer and Adams explicitly teaches the use of clinical trials with teclistamab.
In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dose schedule for the third or maintenance dose from weekly to monthly . Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
The specific method of treatment comprising the administration of the known bispecific antibody of teclistamab where following a step-up dose followed by three doses where the first dose is administered weekly, the second is administered bi-weekly, and the third dose is administered monthly of the would have been obvious absent unexpected results. Unexpected results can overcome a rejection under 35 U.S.C. 103 for claims commensurate with the scope of the unexpected results.
Claim 101-118 are rejected under 35 U.S.C. 103 as being obvious over US 11952426 B2 (IDS) and Adams (WO 2021/228783 A1) (IDS 06/20/2025 FOR # 2).
The applied reference has a common Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Regarding claims 101-105 and 112-113, the reference patent recites a method of treating relapsed refractory multiple myeloma by subcutaneous administration of teclistamab comprising the heavy and light chains of instant claims 102-103 which comprise the CDRs of instant claim 101 (claim 1). The reference patent recites the administration of weekly doses of about 1.5 mg/kg (claim 1) and step-up doses of about 0.06 mg/kg to about 3 mg/kg (claim 13).
Regarding claims 109 and 116, the reference patent recites the administration until the subject achieves stringent complete response (claim 5).
Regarding claims 110 and 117, the reference patent recites the combination with an ant-CD38 antibody (claim 6) or one or more additional cancer therapeutics (claim 7).
The reference patent teaches the use of Clinical Trials to determine the effectiveness of teclistamab (Example 3).
The reference patent does not recite three doses administered weekly, bi-weekly, then monthly for 28 days each, the IMWG diagnostic criteria, or the CD38 binding antibody of daratumumab.
These deficiencies are filled by Adams.
The teachings of Adams from previous rejection under 35 U.S.C. 103 are incorporated here in full.
Adams teaches a method of treating multiple myeloma with the administration of the bispecific antibody teclistamab with step-up doses, three dose levels with varying administration intervals. Adams teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg and a first dose every week, a second dose bi-weekly, and a third dose administered weekly. Adams teaches the first, second, and third administration schedules can have a duration of one to three months which would include 28 days.
Regarding claims 110 and 117, Adams teaches the combination with daratumumab (Example 4).
Adams does not teach a third or maintenance dose administered monthly and does present the specific combination of dose and schedule of teclistamab required by the claims.
It would have been obvious at the time the application was filed to substitute the CD38 binding antibody of the method of treatment of multiple myeloma comprising teclistamab and an anti-CD38 binding antibody and generic diagnostic criteria with the specific anti-CD38 antibody of daratumumab and the IMWG criteria taught by Adams. It would have been prima facie obvious to substitute art equivalent CD38 binding daratumumab and diagnostic criteria of IMWG with the generic versions of the reference patent. There would have been a reasonable expectation of success as the reference patent and Adams are both teaching the treatment of the same patients population with teclistamab.
It would have been obvious at the time the application was filed to optimize the 3rd dose or maintenance dose administered weekly to a monthly administration using known in the art routine experimentation to arrive at a method of treatment where teclistamab is administered at three step-up doses, a first dose administered weekly at 1.5m/kg for 28 days, a second dose administered biweekly at 3 mg/kg, and a third dose of 3 mg/kg administered monthly instead of weekly administration for the third dose as taught by the patent and Adams. One of skill in the art would have been motivated to optimize the teachings of the reference patent and Adams to determine the most effective dosing using the clinical trial method that is well known in the art and taught by the reference patent and Adams. There would have been a reasonable expectation of success as clinical trials are routine experimentation in antibodies used in a method of treating cancer and the patent and Adams explicitly teaches the use of clinical trials with teclistamab.
In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses including the optimization of administering the third or maintenance dose of the method of Adams monthly instead of weekly. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
The specific method of treatment comprising the administration of the known bispecific antibody of teclistamab where following a step-up dose followed by three doses where the first dose is administered weekly, the second is administered bi-weekly, and the third dose is administered monthly of the would have been obvious absent unexpected results. Unexpected results can overcome a rejection under 35 U.S.C. 103 for claims commensurate with the scope of the unexpected results.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
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 101-118 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11952426 B2 (IDS) in view of (WO 2021/228783 A1) (IDS 06/20/2025 FOR # 2).
Regarding claims 101-105 and 112-113, the reference patent recites a method of treating relapsed refractory multiple myeloma by subcutaneous administration of teclistamab comprising the heavy and light chains of instant claims 102-103 which comprise the CDRs of instant claim 101 (claim 1). The reference patent recites the administration of weekly doses of about 1.5 mg/kg (claim 1) and step-up doses of about 0.06 mg/kg to about 3 mg/kg (claim 13).
Regarding claims 109 and 116, the reference patent recites the administration until the subject achieves stringent complete response (claim 5).
Regarding claims 110 and 117, the reference patent recites the combination with an ant-CD38 antibody (claim 6) or one or more additional cancer therapeutics (claim 7).
The reference patent does not recite three doses administered weekly, bi-weekly, then monthly for 28 days each, the IMWG diagnostic criteria, or the CD38 binding antibody of daratumumab.
These deficiencies are filled by Adams.
The teachings of Adams from previous rejection under 35 U.S.C. 103 are incorporated here in full.
Adams teaches a method of treating multiple myeloma with the administration of the bispecific antibody teclistamab with step-up doses, three dose levels with varying administration intervals. Adams teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg and a first dose every week, a second dose bi-weekly, and a third dose administered weekly. Adams teaches the first, second, and third administration schedules can have a duration of one to three months which would include 28 days.
Regarding claims 110 and 117, Adams teaches the combination with daratumumab (Example 4).
Adams does not teach a third or maintenance dose administered monthly and does present the specific combination of dose and schedule of teclistamab required by the claims.
It would have been obvious at the time the application was filed to substitute the CD38 binding antibody of the method of treatment of multiple myeloma comprising teclistamab and an anti-CD38 binding antibody and generic diagnostic criteria with the specific anti-CD38 antibody of daratumumab and the IMWG criteria taught by Adams. It would have been prima facie obvious to substitute art equivalent CD38 binding daratumumab and diagnostic criteria of IMWG with the generic versions of the reference patent. There would have been a reasonable expectation of success as the reference patent and Adams are both teaching the treatment of the same patients population with teclistamab.
It would have been obvious at the time the application was filed to optimize the therapeutic method of the reference patent in view of the clinical trials taught by Adams to have step-up doses and three cycles of administration of teclistamab where the first is weekly, the second is bi-weekly, and the third is weekly as taught by Adams and routine optimization through known in the art experimentation for the third dose of Adams changing the third dose from weekly administration to monthly. One of skill in the art would have been motivated to optimize by the teachings of Adams to determine the most effective dosing using clinical trials as they are explicitly taught to optimize dosing of teclistamab depending on patient population by Adams. There would have been a reasonable expectation of success as clinical trials are routine experimentation in antibodies used in a method of treating cancer and Adams explicitly teaches the use of clinical trials for teclistamab.
In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Further, optimizing the schedule of administration for the third or maintenance dose schedule of teclistamab to administer monthly instead of the weekly taught by Adams. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
The specific method of treatment comprising the administration of the known bispecific antibody of teclistamab where following a step-up dose followed by three doses where the first dose is administered weekly, the second is administered bi-weekly, and the third dose is administered monthly of the would have been obvious absent unexpected results. Unexpected results can overcome a rejection under 35 U.S.C. 103 for claims commensurate with the scope of the unexpected results.
Claims 101-118 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12098210B2 (IDS) in view of (WO 2021/228783 A1) (IDS 06/20/2025 FOR # 2).
Regarding claims 101-104, 106-108, 111, 113-115, and 118, the reference patent recites teclistamab of the CDRs and heavy and light chains of the instant by reciting SEQ ID NO: 27 which matches instant SEQ ID NO: 13, SEQ ID NO: 26 which matches instant SEQ ID NO: 12, SEQ ID NO: 36 which matches instant SEQ ID NO: 22, and SEQ ID NO: 37 which matches instant SEQ ID NO: 21 (claim 5). The reference patent recites step-up doses of about 0.06 mg and 0.3 mg/kg, followed by a cycle of weekly 1.5 mg/kg doses, a cycle of weekly dose of about 3 mg/kg, then a third cycle of about 3 mg/kg once every two weeks (claim 1).
Regarding claims 105 and 112, the reference patent recites the treatment of relapsed or refractory multiple myeloma (claims 1 and 10).
Regarding claims 110 and 117, the reference recites administration with an anti-CD38 antibody (claim 1).
The reference patent does not recite three doses administered weekly, bi-weekly, then monthly for 28 days each, the IMWG diagnostic criteria, or the CD38 binding antibody of daratumumab.
These deficiencies are filled by Adams.
The teachings of Adams from previous rejection under 35 U.S.C. 103 are incorporated here in full.
Adams teaches a method of treating multiple myeloma with the administration of the bispecific antibody teclistamab with step-up doses, three dose levels with varying administration intervals. Adams teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg and a first dose every week, a second dose bi-weekly, and a third dose administered weekly. Adams teaches the first, second, and third administration schedules can have a duration of one to three months which would include 28 days.
Regarding claims 110 and 117, Adams teaches the combination with daratumumab (Example 4).
Adams does not teach a third or maintenance dose administered monthly and does present the specific combination of dose and schedule of teclistamab required by the claims.
It would have been obvious at the time the application was filed to substitute the CD38 binding antibody of the method of treatment of multiple myeloma comprising teclistamab and an anti-CD38 binding antibody and generic diagnostic criteria with the specific anti-CD38 antibody of daratumumab and the IMWG criteria taught by Adams. It would have been prima facie obvious to substitute art equivalent CD38 binding daratumumab and diagnostic criteria of IMWG with the generic versions of the reference patent. There would have been a reasonable expectation of success as the reference patent and Adams are both teaching the treatment of the same patients population with teclistamab.
It would have been obvious at the time the application was filed to optimize the 3rd dose or maintenance dose administered every two weeks by the patent to a monthly administration using known in the art routine experimentation. One of skill in the art would have been motivated to optimize the teachings of the reference patent and Adams to determine the most effective dosing using the clinical trial method that is well known in the art and taught by the reference patent and Adams. There would have been a reasonable expectation of success as clinical trials are routine experimentation in antibodies used in a method of treating cancer and the patent and Adams explicitly teaches the use of clinical trials with teclistamab.
In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. The optimization from administering the third dose once every two weeks to administering it monthly as required by the claims. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
The specific method of treatment comprising the administration of the known bispecific antibody of teclistamab where following a step-up dose followed by three doses where the first dose is administered weekly, the second is administered bi-weekly, and the third dose is administered monthly of the would have been obvious absent unexpected results. Unexpected results can overcome a rejection under 35 U.S.C. 103 for claims commensurate with the scope of the unexpected results.
Claims 101-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-92 of copending Application No. 18639233 in view of Adams (WO 2021/228783 A1) (IDS 06/20/2025 FOR # 2).
Regarding claims 101-104, 106-108, 111, 113-115, and 118, the reference application recites a method of treating multiple myeloma the BCMAxCD3 bispecific antibody of teclistamab administered weekly at a dose of about 0.75 mg/kg to 1.5 mg/kg for 28 days, then administered at a dose of about 1.5 to 3.0 mg/kg every two weeks, and step-up doses of 0.06 mg/kg and .3 mg/kg, and 1.5 mg/kg administered 2 days apart (claims 1-15, 38-39, and 46-49).
Regarding claims 105 and 112, the reference patent recites the treatment of relapsed or refractory multiple myeloma (claim 30).
Regarding claims 109 and 116, the reference application recites complete response to the method of treatment as assessed by IMWG (claim 77).
Regarding claims 110 and 117, the reference application recites combination treatment with the bispecific teclistamab (claim 1).
The reference patent does not recite a third dose administered monthly or the CD38 binding antibody of daratumumab.
These deficiencies are filled by Adams.
The teachings of Adams from previous rejections under 35 U.S.C. 103 and Double Patenting are incorporated here in full.
Adams teaches a method of treating multiple myeloma with the administration of the bispecific antibody teclistamab with step-up doses, three dose levels with varying administration intervals. Adams teaches the subcutaneous administration of the bispecific antibody at any amount from about 0.1 µg/kg to about 5000 µg/kg which would be about 0.0001 mg/kg to about 5 mg/kg and a first dose every week, a second dose bi-weekly, and a third dose administered weekly. Adams teaches the first, second, and third administration schedules can have a duration of one to three months which would include 28 days.
Regarding claims 110 and 117, Adams teaches the combination with daratumumab (Example 4).
Adams does not teach a third or maintenance dose administered monthly and does present the specific combination of dose and schedule of teclistamab required by the claims.
It would have been obvious at the time the application was filed to combine the composition used in the method of treating multiple myeloma of the reference application comprising teclistamab with the anti-CD38 antibody of daratumumab taught by Adams. It would have been prima facie obvious to combine treatments for use in the same patient population of multiple myeloma. There would have been a reasonable expectation of success as the reference application and Adams are both teaching the treatment of the same patients population with teclistamab.
It would have been obvious at the time the application was filed to modify the method of the reference application to add a third dose and optimize the 3rd dose or maintenance dose administered weekly to a monthly administration in view of Adams and using known in the art routine experimentation to arrive at a method of treatment where teclistamab is administered at three step-up doses, a first dose administered weekly at 1.5m/kg for 28 days, a second dose administered biweekly at 3 mg/kg, and a third dose of 3 mg/kg administered monthly instead of weekly administration for the third dose as taught by the reference patent and Adams. One of skill in the art would have been motivated to optimize the teachings of the reference application and Adams to determine the most effective dosing using the clinical trial method well known in the art and taught by Adams. There would have been a reasonable expectation of success as clinical trials are routine experimentation in antibodies used in a method of treating cancer and Adams explicitly teaches the use of clinical trials with teclistamab.
In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
The specific method of treatment comprising the administration of the known bispecific antibody of teclistamab where following a step-up dose followed by three doses where the first dose is administered weekly, the second is administered bi-weekly, and the third dose is administered monthly of the would have been obvious absent unexpected results. Unexpected results can overcome a rejection under 35 U.S.C. 103 for claims commensurate with the scope of the unexpected results.
This is a provisional nonstatutory double patenting rejection.
Claims 101-104, 106-108, 110-111, 113-115, and 117-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-122 of copending Application No. 19126633 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 101-104, 106-108, 111, 113-115, and 118, the reference application recites a method of treating multiple myeloma by administering the BCMAxCD3 bispecific antibody of teclistamab at a dose of 0.06 mg/kg to 6 mg /kg at an interval of daily, weekly, biweekly, once every 4 weeks, or monthly, and further comprises step-up doses of about 0.06 mg/kg to 6 mg/kg and administered every 2 days (claims 1-18) and administered subcutaneously (claims 33). The reference patent recites up to 4 treatment cycles (claim 106) and a 28 day treatment cycle (claims 108). The reference patent recites the treatment of multiple myeloma (claim 115).
Regarding claims 110 and 117, the reference application the combination with daratumumab (claims 95).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 101, 104-105, 109, 112, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-122 of copending Application No. 19126633 (reference application) in view of Adams (WO 2021/228783 A1) (IDS 06/20/2025 FOR # 2).
Regarding claims 101 and 104-105, Regarding claims 101-104, 106-108, 111, 113-115, and 118, the reference application recites a method of treating multiple myeloma by administering the BCMAxCD3 bispecific antibody of teclistamab at a dose of 0.06 mg/kg to 6 mg /kg at an interval of daily, weekly, biweekly, once every 4 weeks, or monthly, and further comprises step-up doses of about 0.06 mg/kg to 6 mg/kg and administered every 2 days (claims 1-18) and administered subcutaneously (claims 33). The reference patent recites up to 4 treatment cycles (claim 106) and a 28 day treatment cycle (claims 108). The reference patent recites the treatment of multiple myeloma (claim 115).
The reference application does not recite the treatment of relapsed or refractory multiple myeloma or the assessment using the diagnostic treatment by IMWG.
These deficiencies are filled by Adams.
The teachings of Adams from previous rejections under 35 U.S.C. 103 and Double Patenting are incorporated here in full.
Regarding claims 105 and 112, Adams teaches the treatment of relapsed or refractory multiple myeloma (page 19 in lines 29-33).
Regarding claims 109 and 116, Adams teaches the subject being treated attains a stringent complete response according (page 4 in lines 11-16) and teaches the IMWG diagnostic criteria for multiple myeloma for use in assessing patients (page 44 in line 11).
It would have been obvious at the time the application was filed to combine the method of treating multiple myeloma of the reference patent with the method of treatment where the patients have relapsed or refractory multiple myeloma with diagnostic assessment by IMWG as taught by Adams. One of skill in the art would have been motivated by the teaching of Adams teaching a method of treatment comprising the same bispecific as the reference patent in a patient population in need for treatment and a method of assessing patient outcome. There would have been a reasonable expectation of success as the reference application and Adams both teach the treatment of multiple myeloma with teclistamab.
This is a provisional nonstatutory double patenting rejection.
Claims 101-118 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-176 of copending Application No. 19581814 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 101-108, 111-115, and 118, the reference application recites a method of treating multiple myeloma by administering the BCMAxCD3 bispecific antibody of teclistamab (claims 1-2) administered subcutaneously on 28 day cycles (claim 1) at step-up doses of 0.72 mg/kg, 1.5 mg/kg, or 3.0 mg/kg (claims 31-36), and then a weekly dose (claim 36) of 1.5 mg/kg, biweekly dose of about 3 mg/kg (claims 32, 65, and 84), and monthly 3 mg/Kg (claim 88). The reference patent recites the treatment of relapsed or refractory multiple myeloma (claim 168).
Regarding claims 109 and 116, the reference patent recites the assessment of complete response as defined by IMWG (claims 72-73).
Regarding claims 110 and 117, the reference patent recites combining with daratumumab (claim 62).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
