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
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-8, and 10-13 have an effective filing date of 03NOV2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/27/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 8/15/2023, Applicant elected, without traverse:
Method of treatment, claims 2 and 7-17 read on the elected species
Status of Claims
Claims 1-8, and 10-13 are currently pending and presented for examination on the merits.
Claims 1 and 3-6 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claims 9 and 14-17 are canceled.
Rejections Maintained
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.
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 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 2, 7-8, and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Audit et al (US 20200239589 A1, Previous OA), and further in view of Fau et al (Drug-Disease Interaction and Time-Dependent Population Pharmacokinetics of Isatuximab in Relapsed/Refractory Multiple Myeloma Patients, CPT Pharmacometrics Syst Pharmacol (2020) 9, 649–658, IDS 8/16/2023).
Audat et al teaches methods of treating multiple myeloma with an anti-CD38 antibody [0008]. Audat et al further teaches administering the anti-CD38 antibody at 10 mg/kg [0008]. Audat et al further teaches the anti-CD38 antibody is isatuximab [0019]. Audat et al further teaches isatuximab administered days 1, 8, 15, 22 of the first month cycle [0020]. Audat et al further teaches administering isatuximab at 10 mg/kg after the first month once every two weeks [Table C]. Audat et al further teaches the method extending PFS of the individual [0007]. Audat et al further teaches maintenance administration of the anti-CD38 antibody as patients continued treatment until disease progression, unacceptable adverse events (e.g., unacceptable toxicity), or patient wish, whichever came first [0133]. Audat et al further teaches administering isatuximab once every two weeks for one or more one-month cycles after the first month cycle [Table C]. Audat et al further teaches patients that achieved VGPR or better after receiving isatuximab [0032, Fig. 6A].
Audat et al does not specifically teach administering the CD38 antibody at a dose of 10 mg/kg once a month once VGPR is maintained for at least six months. However, this deficiency is made up in the teachings of Fau et al.
Fau et al teaches the treatment of multiple myeloma comprising administering isatuximab [Abstract]. Fau et al further teaches patients received 1-20 mg/kg dosage of isatuximab [Abstract]. Fau et al further teaches a typical 50% decrease in linear clearance from initial treatment to steady-state for isatuximab [Abstract]. Fau et al further teaches isatuximabs pharmokinetics were well-characterized by a two-compartment structural kinetic model with parallel linear and nonlinear eliminations from the central compartment [Discussion, pg. 655]. Fau et al further teaches linear clearance is the predominant clearance method for isatuximab accounting for 90% of clearance [Discussion, pg. 655]. Fau et al further teaches a decrease in isatuximabs linear clearance of about 50% [Figure 2 (a), pg. 654]. Fau et al further teaches isatuximab plasma concentration demonstrated that the saturation of the target (> 80% of target occupancy), was reached for concentrations corresponding to the ≥ 10 mg/kg q.w. dose level [Discussion, pgs. 655-656]. Fau et al further teaches isatuximab, the magnitude of CL change over time was larger than for other mAbs, and an average 50% decrease was estimated for isatuximab from the first dose to steady state [Right column, 2nd paragraph, pg. 656].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Audat’s methods for a method of treating multiple myeloma comprising administering isatuximab at a dose of 10 mg/kg QW for a first one-month cycle, and then 10 mg/kg Q2W for subsequent cycles and achieving VGPR, with Fau’s method of decreasing dosages based upon a decrease in clearance and an increase in plasma concentration of isatuximab from 1st dose to steadystate. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Audat and Fau’s methods for a method of treating a human individual having multiple myeloma comprising administering isatuximab at 10 mg/kg for a first one-month cycle, then at 10 mg/kg for one or more one-month cycle until VGPR is maintained for at least 6 months, based on monitoring, then administering the isatuximab at 10 mg/kg QM for one or more one-month cycles. One of ordinary skill in the art would appreciate that the administration schedule and dosage of a therapeutic regimen represent optimizable variables that affect the safety and efficacy of a therapeutic regimen, and one of ordinary skill in the art would thus recognize the utility of optimizing the administration schedule and dosage of medicaments in a therapeutic regimen. The invention of the conflicting claims, Audit and Fau meets the limitations of claims 2, and 10-13.
With respect to claim 7, Audat et al teaches blood samples from patients that were used to assess the pharmokinetics of isatuximab [0121].
With respect to claim 8, Audat et al teaches the assessment of M-protein by immunofixation and electrophoresis [0128].
Applicant’s Arguments:
Applicant respectfully traverses.
Examiner has not properly established a prima facie case of obviousness under 35 U.S.C. § 103.
… none of the cited references specifically disclose modifying the dosing schedule for the isatuximab from the standard dosing schedule based on a sustained very good partial response (VGPR) in the patient.
First, the Examiner has not articulated how the methods of Audat and Fau are equivalents known for the same purpose. The Examiner has not articulated the supposed same purpose of Audat and Fau. Audat is completely silent on decreasing dosage of isatuximab.
Second, the prior art elements cannot be combined to yield predictable results because all of the elements of the claimed invention are not specifically disclosed by the cited references. As stated in § MPEP 2143.
"Routine optimization" cannot be used to cure deficiency
Applicant respectfully submits that in order to properly support a rejection on the basis that an invention is the result of "routine optimization", the Examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail.
The Examiner points to several passages in Fau for allegedly teaching isatuximab pharmacokinetics and clearance pattern, etc., vet none of the passages has any specific disclosure related to modifying a dosing schedule in response to a patient's sustained response.
Examiner’s Response:
Audat et al teaches patients that achieved VGPR or better after receiving isatuximab, and Audat et al. further teaches maintenance administration of the anti-CD38 antibody as patients continued treatment until disease progression, unacceptable adverse events (e.g., unacceptable toxicity), or patient wish, whichever came first [0133]. Audat et al further teaches aministering isatuximab once every two weeks for one or more one-month cycles after the first month cycle [Table C].
Applicant states, “none of the cited references specifically disclose modifying the dosing schedule for the isatuximab from the standard dosing schedule based on a sustained very good partial response (VGPR) in the patient”.
The claim limitation of “modifying the dosing schedule”
See MPEP 2143 I. A. Example 6
Rationales that support a conclusion of obviousness.
In the case of Ecolab, Inc. v. FMC Corp., 569 F.3d 1335, 91 USPQ2d 1225 (Fed. Cir. 2009), an "apparent reason to combine" in conjunction with the technical ability to optimize led to the conclusion that the claimed invention would have been obvious.
When considering the question of obviousness, Office personnel should keep in mind the capabilities of a person of ordinary skill. In Ecolab, the Federal Circuit stated:
Ecolab’s expert admitted that one skilled in the art would know how to adjust application parameters to determine the optimum parameters for a particular solution. The question then is whether it would have been obvious to combine the high pressure parameter disclosed in the Bender patent with the PAA methods disclosed in FMC’s ’676 patent. The answer is yes. Id.
If optimization of the application parameters had not been within the level of ordinary skill in the art, the outcome of the Ecolab case may well have been different.
Applicant argues that one of ordinary skill in the art, providing medical treatment to an individual with multiple myeloma, would not know to adjust treatment parameters to determine the optimum parameters for the treatment.
Examiner disagrees, one of ordinary skill in the art, before the effective filing date, would have optimized the application parameters of for a method of treating a human individual having multiple myeloma. It would have been obvious for a physician to adjust the dosage based on patient response.
Applicant argues, “the basis that an invention is the result of "routine optimization", the Examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail.”.
Examiner disagrees, the limitation of “modifying the dosing schedule” is calibrating the proper dosage of isatuximab does not amount to more than routine dosage optimization by one of ordinary skill in the art. For the treatment of multiple myeloma, one of ordinary skill in the art is a Physician. Physicians routinely optimize the dosage of medication for patients based on patient response to treatment.
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 2, 7-8, and 10-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of copending Application No. 17/259,135 in view of Audit et al (US 20200239589 A1, Previous OA) and Fau et al (Drug-Disease Interaction and Time-Dependent Population Pharmacokinetics of Isatuximab in Relapsed/Refractory Multiple Myeloma Patients, CPT Pharmacometrics Syst Pharmacol (2020) 9, 649–658, IDS 8/16/2023).
The teachings of Audat et al and Fau et al are discussed above.
Claims 2, 10-12 are directed to an invention that is not patentably distinct from claims 1-4 of provisional co-pending application 17/259,135. Specifically, a method of treating multiple myeloma comprising administering an anti-CD38 antibody, wherein the anti-CD38 antibody is isatuximab. It would have been prima facie obvious to combine Audat and Fau’s methods for a method of treating a human individual having multiple myeloma comprising administering isatuximab at 10 mg/kg for a first one-month cycle, then at 10 mg/kg for one or more one-month cycle until VGPR is maintained for at least 6 months, based on monitoring, then administering the isatuximab at 10 mg/kg QM for one or more one-month cycles, because Audat teaches these administration regimens and dosage. Furthermore, Fau et al teaches method of decreasing dosages based upon a decrease in clearance and an increase in plasma concentration of isatuximab from 1st dose to steady state. One of ordinary skill in the art would appreciate that the administration schedule and dosage of a therapeutic regimen represent optimizable variable that affect the safety and efficacy of a therapeutic regimen, and one of ordinary skill in the art would thus recognize the utility of optimizing the administration schedule and dosage of medicaments in a therapeutic regimen.
With respect to claim 7, Audat et al teaches blood samples from patients that were used to assess the pharmokinetics of isatuximab [0121].
With respect to claim 8, Audat et al teaches the assessment of M-protein by immunofixation and electrophoresis [0128].
With respect to claim 13, Audat et al teaches the method extending PFS of the individual [0007].
This is a provisional nonstatutory double patenting rejection.
Applicant’s Arguments:
As discussed above, Audat and Fau, either alone or in combination, do not specifically disclose all the limitations recited in independent claim 2.
Applicant respectfully submits that the pending claims in the present application and the pending claims in Application No. 17/259,135 (US 20210155708) are patentably distinct.
Examiner’s Response:
Please see arguments above.
The claim limitation of, “modifying the dosing schedule”, is a mere data gathering step, See MPEP 2106.05(g). Assessing data to be used in a diagnosis.
Applicant states the pending claims in Application No. 17/259,135 (‘135) is patentably distinct from the instant claims.
Instant claim 2 is directed to an invention that is not patentably distinct from claim 1 of ‘135. Specifically, a method of treating cancer comprising administering an anti-CD38 antibody. In view of the teachings of Audat et al administering isatuximab at 10 mg/kg after the first month once every two weeks [Table C]. Combined with, Fau et al teaching a decreasing in drug clearance over 24 weeks [Figure S5].2, 7-8, and 10-13
Conclusion
Claims 2, 7-8, and 10-13 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DENNIS J SULLIVAN/ Examiner, Art Unit 1642
/NELSON B MOSELEY II/ Primary Examiner, Art Unit 1642
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