DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Claims 1-21 are pending and under current examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 20 lacks a period at the end of the claim, therefore it is unclear whether the claim requires any additional limitations other than those recited in the claim. See MPEP 608.01(m).
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-6 and 8-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Dadey (WO/2008/153611; publication date: 12/18/2008; cited in the IDS filed 01/24/2024).
With regard to claims 1, 2, 4, 16, and 21, Dadey discloses a method of administering to a patient in need thereof a composition to provide a biodegradable solid implant upon injection comprising risperidone, a metabolite or a prodrug thereof, a solvent, and a biodegradable polymer wherein the implant delivers a therapeutically effective dosage of risperidone, a metabolite or a prodrug thereof (i.e. it forms an extended release depot composition; Dadey: claim 54 and 56). In some examples, the depot is administered as an intramuscular injection (page 52). The polymer is PLG (poly(lactide co-glycolide) having ratios of lactic acid to glycolic acid monomers ranging from 50:50 to 75:25 (table 42, pages 225-228). Dadey teaches DMSO as a solvent for use in their invention (Dadey: page 34, line 20). At least a fraction of the risperidone in the composition is in suspension (i.e. particles of risperidone are present; page 221, line 11). Dadey discloses that risperidone is administered at from 1 to 16 mg per day (page 44) and discloses depot doses of 30, 60, or 120 mg tested in animals (e.g. page 146). This would give one of ordinary skill a starting point to optimize the dose in the depot composition to administer to a human being treated with risperidone in order to achieve a therapeutic effect, and therefore the examiner does not consider the specific doses recited in the instant claims to patentably define over Dadey. See MPEP 2144.05. Regarding each of the ratios and amounts of drug, DMSO, and polymer recited in the claims, as noted above, Dadey indicates that risperidone depots with drug concentration of 15% by weight relative to the total weight of the composition give lower initial burst, and lower polymer/solvent ratios result in improved handling in the syringe (page 145, lines 4-7). Based on example formulations disclosed by Dadey, this information would lead the skilled Artisan to explore drug concentrations in the vicinity of 15%, and polymer/solvent weight ratios in the vicinity of 40/60. A depot that is 15% drug in 40/60 polymer/solvent has concentrations of 15% drug, 34% polymer, and 51% solvent. Making a minor adjustment in the drug concentration to 13% while leaving polymer/solvent ratio constant, would result in a composition with 13% drug, 35% polymer, and 52% solvent. This composition has a drug:solvent ratio of 1:4, a drug polymer ratio of 37% (i.e. about 33%), and a drug:(polymer + solvent) ratio of 1:6.69. A minor adjustment to the amount of drug during optimization of dose, release characteristics, and syringe handling when switching from the NMP used in Dadey’s examples to one of Dadey’s other most preferred solvents such as DMSO would have been routine for one of skill in the art and not inventive within the meaning of 35 USC 103(a), absent unexpected results that are commensurate in scope with the claims. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical (see MPEP 2144.05(II)(A). The instant claims place limitations on the viscosity of the solution comprising the polymer and the solvent. Dadey does not explicitly disclose the viscosities of the final compositions or of the polymer/solvent component in the absence of drug. However, this property would necessarily also be optimized as a direct consequence of optimizing the amounts of the only ingredients in the formulation: risperidone, DMSO, and a PLGA polymer having an inherent viscosity falling within the indicated in the instant specification to provide the requisite viscosity to the polymeric solution. Regarding the limitation requiring plural dosing periods, Dadey discloses that the objective of the invention is to provide a depot that produces therapeutic levels of risperidone for 14 days to 3 months (page 3). It would have been prima facie obvious to administer an additional dose when the implant ceases to provide therapeutic plasma concentrations of risperidone, within the time frame of 14 days to 3 months, depending upon how the composition is formulated.
With regard to claims 3 and 4, as noted above, Dadey’s composition can be designed to release risperidone for between 14 days up to 3 months. As the limitation “wherein each dosing period is at 4 weeks” overlaps with the range disclosed by Dadey, this dosing frequency is considered prima facie obvious.
With respect to the limitations of instant claims 1, 4, 8-14, and 17-20 regarding dosing regimen, drug release kinetics, and drug plasma profiles, without a laboratory, it is not possible for the USPTO to determine what the plasma drug concentrations would be upon administering the composition rendered obvious by the teachings of Dadey. Dadey’s objective is to provide long term, steady release of risperidone from a composition consisting of risperidone particles, PLGA polymer, and solvent that forms a depot upon injection. As is well-known in the art of pharmaceutics, adverse effects and loss of therapeutic effect have been associated with plasma concentration peaks and troughs. Therefore, one of skill in the art would have the objective of developing a depot composition with zero order release kinetics with guidance from the teachings of Dadey. As the structural characteristics required by the instant claims have been rendered obvious by the teachings of Dadey, the limitations regarding drug plasma concentrations also flow readily therefrom and would have been optimizable by measuring the pharmacokinetic profiles obtained from the various compositions falling within the scope of Dadey’s invention.
With regard to claims 5 and 6, Dadey’s method includes mixing, in any order, the biodegradable thermoplastic polymer (e.g. the PLGA), a biocompatible polar aprotic liquid (e.g. the DMSO), and risperidone, a metabolite, or a prodrug thereof (page 6). Dadey teaches a syringe containing the thermoplastic polymer and solvent and a different syringe containing risperidone. The contents of the syringes are subsequently mixed and then administered to form the depot in situ (page 38, lines 4-15). Thus, the examiner considers Dadey to disclose a kit in the form of two syringes; see also claim 37 which claims a kit having polymer in a first container and risperidone in a second container.
With respect to the limitation of instant claims 4 and 15 that less than or equal to 20 % of the risperidone is dissolved in the injectable composition, the examiner considers Dadey to disclose a range in dissolved risperidone that overlaps with the range required by the instant claims when Dadey’s solvent is DMSO because this is a physical characteristic of risperidone when suspended in DMSO and Dadey discloses an overlapping range of concentration of risperidone in the DMSO.
Claim 7 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Dadey (WO/2008/153611; publication date: 12/18/2008; cited in the IDS filed 01/24/2024) as applied to claims 1-6 and 8-21 above, and further in view of Bodmeier (US PGPub No. 2004/0010224; publication date: 01/15/2004; cited in the IDS filed 01/24/2024).
The relevant disclosure of Dadey is set forth above and renders obvious a method of treating schizophrenia or bipolar disorder, the method comprising providing a kit comprising a PLGA copolymer, risperidone, and DMSO; mixing the these substances to form an extended release injectable suspension consisting essentially of particles of risperidone suspended in a polymeric solution of said DMSO and said PLGA copolymer, wherein ≥ 1% wt and ≤ 20% wt of the risperidone is dissolved in said DMSO or said polymeric solution; and administering to said subject by intramuscular injection a dose of said suspension comprising 25-150 mg of said risperidone; wherein after said administering said composition forms an implant in said subject, wherein said implant provides therapeutically effective levels of active moiety, which is risperidone and/or 9-hydroxyrisperidone, from the first day up to at least 28 days after said administering, and wherein said administering is done every 4 to 5 weeks or every 4 weeks.
Dadey teaches a syringe containing the thermoplastic polymer and solvent and a different syringe containing risperidone. The contents of the syringes are subsequently mixed and then administered to form the depot in situ (page 38, lines 4-15). Thus, the examiner considers Dadey to disclose a kit in the form of two syringes; see also claim 37 which claims a kit having polymer in a first container and risperidone in a second container. In the examples cited above, Dadey discloses a syringe in which the polymer and solvent have been mixed, and then this is mixed with risperidone, thus the order of steps, and consequent arrangement of syringes, differs from instant claim 7 because the instant claims require the risperidone and polymer to be in a separate syringe from the DMSO solvent.
Bodmeier et al. report storing polymer separately from solvent (para 0019, lines 1-4) in a kit for in situ formation of an implant in a subject after exposure to a carrier phase (para 0015, lines 2-8). The Artisan of skill would have been motivated to store the polymer and solvent in the kit disclosed by Dadey et al. in separate containers because Bodmeier et al. disclose that this can reduce degradation or chemical modification of the polymer and also the polymer and drug can be incorporated into the solvent in a single step, simplifying preparation (para 0019, lines 6-20). If the drug and/or polymer were stored separately from the solvent they would be in solid form as these substances are solids at room temperature.
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 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-26 of U.S. Patent No. 10,195,138;
claims 1-40 of U.S. Patent No. 10,335,366;
claims 1-25 of U.S. Patent No. 10,881,605;
claims 1-26 of U.S. Patent No. 10,463,607;
claims 1-13 of U.S. Patent No. 10058504;
claims 1-20 of U.S. Patent No. 10085936;
claims 1-21 of U.S. Patent No. 10182982;
claims 1-49 of U.S. Patent No. 11007139;
claims 1-53 of U.S. Patent No. 11173110;
claims 1-20 of U.S. Patent No. 11241377;
claims 1-22 of U.S. Patent No. 11752092
claims 1-22 of U.S. Patent No. 11752093;
claims 1-30 of U.S. Patent No. 11752094;
claims 1-32 of U.S. Patent No. 11759416;
claims 1-17 of U.S. Patent No. 12318387;
claims 1-26 of U.S. Patent No. 12318478
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Inter alia, the claims of the ‘138, ‘377, ‘366, ‘605, ‘607, ‘504, and ‘936 patents embrace a method of administering risperidone to a human subject by intramuscular injection of a depot forming composition containing risperidone particles in DMSO and PLGA polymer having LA:GA of 50:50 to 75:25, wherein the amount of risperidone and ratio of risperidone, DMSO, and PLGA are the same as those required by the instant claims. The composition can be administered at least every four weeks (i.e. a plurality of doses are administered) and provides a therapeutic plasma concentration of risperidone and/or its active metabolite for at least that duration. The pharmacokinetic profile and dosing schedule are claimed and/or readily optimizable as the compositions are identical or nearly identical to those of the instant claims. Prior to administration, the composition may be in the form of a kit wherein PLGA and risperidone are stored in one syringe and DMSO are in a second separate syringe.
The claims of the‘366, ‘605, ‘607, ‘504, and ‘936 patents are directed towards compositions; however, the specifications of each of the aforementioned patents indicates that the inventions embrace the methods noted above. The examiner has relied upon the specification to delineate the scope of the invention embraced by the patents, consistent with the decision in Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co. U.S. Court of Appeals Federal Circuit, 95 USPQ2d 1797.
With regard to the ‘982 and ‘110 patents, and the location of risperidone, DMSO, and polymer in the containers of the kit as well as the implicit order of steps of combining, any order of steps (and implicit location of storage) is considered prima facie obvious. See MPEP 2144.04(IV)(A).
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-26 of U.S. Patent No. 11,013,683; and
claims 1-16 of U.S. Patent No. 10,350,159
in view of Sathyan et al. (US 2005/0208132; publication date: 09/22/2005).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Inter alia, the claims of the ‘683, and ‘159 patents embrace a method of administering paliperidone to a human subject by intramuscular injection of a depot forming composition containing paliperidone particles in DMSO and PLGA polymer having LA:GA of 50:50 to 75:25, wherein the amount of paliperidone and ratio of paliperidone, DMSO, and PLGA are the same as those required by the instant claims. The composition can be administered at least every four weeks (i.e. a plurality of doses are administered) and provides a therapeutic plasma concentration of paliperidone and/or its active metabolite for at least that duration. The pharmacokinetic profile and dosing schedule are claimed and/or readily optimizable as the compositions are identical or nearly identical to those of the instant claims. Prior to administration, the composition may be in the form of a kit wherein PLGA and paliperidone are stored in one syringe and DMSO are in a second separate syringe.
The claims of the ‘683, and ‘159 patents recite a limitation requiring the drug paliperidone rather than the risperidone recited in the instant claims.
Sathyan discloses that paliperidone is the major active metabolite of risperidone and that risperidone is extensively metabolized in the liver to an equipotent metabolite, paliperidone, and the sum of the two compounds (active moiety) is thought to provide the clinical effect of risperidone (0007).
It would have been prima facie obvious to substitute risperidone for paliperidone in the ‘683, and ‘159 inventions because one having ordinary skill in the art would have recognized that both agents provide comparable clinical effects.
The claims of the ‘159 patent is directed towards compositions; however, the specification of the aforementioned patent indicates that the invention embraces the methods noted above. The examiner has relied upon the specification to delineate the scope of the invention embraced by the patents, consistent with the decision in Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co. U.S. Court of Appeals Federal Circuit, 95 USPQ2d 1797.
Claims 1-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-13 and 21-36 of copending Application No. 17747422 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims.
Inter alia, the claims of the ‘647, ‘927, ‘514, ‘337, ‘640, and ‘422 applications embrace a method of administering risperidone to a human subject by intramuscular injection of a depot forming composition containing risperidone particles in DMSO and PLGA polymer having LA:GA of 50:50 to 75:25, wherein the amount of risperidone and ratio of risperidone, DMSO, and PLGA are the same as those required by the instant claims. The composition can be administered at least every four weeks (i.e. a plurality of doses are administered) and provides a therapeutic plasma concentration of risperidone and/or its active metabolite for at least that duration. The pharmacokinetic profile and dosing schedule are claimed and/or readily optimizable as the compositions are identical or nearly identical to those of the instant claims. Prior to administration, the composition may be in the form of a kit wherein PLGA and risperidone are stored in one syringe and DMSO are in a second separate syringe.
The claims of the ‘927 application are directed towards a composition; however, the specification the aforementioned application indicates that the inventions embrace the methods noted above. The examiner has relied upon the specification to delineate the scope of the invention embraced by the patents, consistent with the decision in Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co. U.S. Court of Appeals Federal Circuit, 95 USPQ2d 1797.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617