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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/9/26 has been entered.
Status of Claims
Claims 1-3, 5-19, and 21-25 are pending as of the response and amendments filed on 4/9/26. Claims 4 and 20 have been canceled, claims 22-25 have been newly added.
The 103 rejection over Gerhart, WO 2018067341, and over Gerhart in view of Kinsey, US 20170216538 are withdrawn in consideration of the amendments.
Regarding the nonstatutory double patenting rejections of record, Applicants have requested these rejections be held in abeyance until there is otherwise allowable subject matter in the present application. The provisional nonstatutory double patenting rejections over the claims of copending applications 19169921 and 19210846 are maintained and modified to address the amended claims. New 103 rejections are made based on the amended claims, discussed below.
Claims 1-3, 5-19, and 21-25 were examined and are rejected.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 5-19, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wollin et. al., WO 2018108669 A1, publ. 6/21/2018 (cited in an IDS), in view of Kinsey et. al., US 20170216538 A1, publ. 8/3/2017 (of record).
Wollin et. al. teaches the combination of the tyrosine kinase inhibitor, nintedanib and olodaterol for the treatment of interstitial lung diseases (title & abstract; p. 1, lines 9-13; p. 3, lines 7-10; p. 7, lines 4-8):
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. Idiopathic pulmonary fibrosis (IPF) is one of the most common interstitial lung diseases; IPF is characterized by progressive fibrosis of the lung, leading to decreased lung volume and pulmonary insufficiency (p. 2, lines 8-21). Wollin teaches nintedanib exhibited positive results regarding the rate of decline in forced vital capacity (FVC) in patients with IPF (p. 4, lines 11-14). Olodaterol is a beta2-adrenoceptor agonist that has anti-fibrotic properties (p. 4, line 23-p. 5, line 2). Wollin teaches nintedanib and olodaterol in a pharmaceutical composition for inhalative administration, and at least one pharmaceutical excipient; dry powder formulations are also taught (p. 7, lines 10-16). Wollin teaches the therapy as described allows for improved efficiency of treatment as well as reduced side effects; particularly, the combination of nintedanib and olodaterol provides a synergistic anti-fibrotic effect (p. 10, lines 4-9). Wollin further teaches administration of the formulation by inhalation to the lung is expected to exert greater efficacy in preserving lung function and improve the adverse event profile (p. 11, line 25-p. 12, line 2). Wollin teaches the formulations for inhalation, such as dry powders, can comprise carriers or excipients which stabilize the formulation or prolong shelf life (p. 12, lines 11-19). Wollin teaches the daily dose of tyrosine kinase inhibitor, i.e., nintedanib for inhalation ranges from 10 mg. to 100 mg. (p. 15, lines 1-3). Wollin exemplifies a dry powder formulation containing nintedanib and mannitol and L-leucine as excipients (p. 20, lines 1-7). Polysorbate 80 is also included as an excipient (p. 20, lines 24-31). Wollin teaches IPF as the most preferred interstitial lung disease to be treated by the above-described method (p. 14, lines 15-23).
Wollin doesn’t explicitly teach or suggest crystalline diketopiperazine particles.
Kinsey teaches a dry powder inhaler comprising replaceable cartridges containing a dry powder composition for local or systemic delivery, e.g., to the pulmonary tract, wherein the dry powder composition comprising an active agent (title & abstract; para [0002]). Kinsey teaches the dry powder composition and inhaler allow for effective and rapid delivery of a medicament to the lungs (para [0009]). Kinsey teaches the pharmaceutical composition to comprise a pharmaceutically acceptable carrier for oral inhalation (para [0048]), with diketopiperazine exemplified as a carrier (para [0010]). Kinsey further teaches an embodiment wherein the composition with inhaler is to be delivered deeply into the lungs (para [0015]). Kinsey teaches an embodiment wherein the diketopiperazine is in a crystalline form (para [0027]); fumaryl diketopiperazine (FDKP) is additionally exemplified as the diketopiperazine carrier (para [0083]):
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. Kinsey teaches the dry powder formulation to be suitable for delivery of a wide range of therapeutic agents (para [0082]), and that the dry powder formulation is amorphous (para [0058]). Kinsey further teaches the diketopiperazine microparticles to have a specific surface area from about 19 m2/g to about 71 m2/g (para [0081]), with an average pore size ranging from about 23 nm to about 30 nm (para [0094]). Kinsey teaches the dry powder inhaler further comprises a cartridge, lid, and container, wherein the inhaler body has a cartridge mounting area (para [0012-0016]). Kinsey teaches the inhaler dispenses the dry powder composition in less than about 3 seconds, with the amount of composition in the cartridge ranging from between 1 to 50 mg. (para [0026]). Kinsey further teaches the dry powder compositions comprising FDKP and having the cited specific area have improved aerodynamic properties and drug absorption for pulmonary delivery (para [0081], [0085], [0093]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at an inhalable pharmaceutical composition comprising a dry powder, wherein the dry powder comprising pre-formed crystalline fumaryl diketopiperazine particles and a therapeutically effective dose of nintedanib or a pharmaceutically acceptable salt thereof, and to have administered the composition by oral inhalation to treat IPF to a patient in need thereof in consideration of the combined teachings of Wollin and Kinsey. Wollin teaches the combination of nintedanib and olodaterol for treating IPF, including in a dry powder formulation for oral inhalation. Although Wollin doesn’t teach crystalline diketopiperazine particles, Kinsey teaches a dry powder inhaler comprising replaceable cartridges containing a dry powder composition for local or systemic delivery, e.g., to the pulmonary tract, wherein the dry powder composition comprises an active agent and fumaryl diketopiperazine (FKDP) as crystalline particles. Kinsey teaches crystalline FDKP allows for improved aerodynamic properties and drug absorption for pulmonary delivery. As such, it would have been prima facie obvious to a person of ordinary skill in the art to have incorporated the dry powder composition comprising pre-formed crystalline FDKP into the dry powder nintedanib formulation of Wollin, and to have administered the formulation by oral inhalation to treat IPF in a patient, with the reasonable expectation that drug absorption in the lungs would have been improved.
Claim(s) 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wollin et. al., WO 2018108669 A1 in view of Kinsey et. al., US 20170216538 A1 as applied to claims 1-3, 5-19, and 21, further in view of Wade et. al., WO 2008098196 A1, publ. 8/14/2008.
The teachings of Wollin and Kinsey as discussed previously are incorporated herein. However, neither explicitly teaches or suggests further administering a prostaglandin analog for treating IPF.
Wade teaches administration of Treprostinil for treating interstitial lung disease such as pulmonary fibrosis and IPF (title & abstract; para [0002-0005], [0010]). Wade teaches Treprostinil can be administered by inhalation in solid or liquid dosage forms (para [0011], [0014], [0035]). Treatment of pulmonary fibrosis and IPF are exemplified (para [0049-0051], [0077-0082]). Wade teaches Treprostinil can be administered in combination with other agents used to treat pulmonary disease, and that such treatment normalizes biomarkers associated with pulmonary disease (para [0012]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have further administered by inhalation a separate formulation comprising the prostaglandin analog, Treprostinil, to treat a subject in need of treatment for IPF. Wollin teaches treatment of IPF by oral inhalation of a dry powder formulation of nintedanib, while Wade teaches inhalation of a formulation of Treprostinil for the treatment of IPF. Wade further teaches administration of combination therapies for treatment. As such, one of ordinary skill in the art would have arrived at the claimed method of treatment, and have added the step of administering a formulation by oral inhalation of Treprostinil for treatment of IPF, and have had a reasonable expectation of success. Regarding the limitation of instant claim 24, Wollin teaches inhalation administration of compositions can be applied with the use of state of the art nebulizers (see p. 12, lines 24-33). Therefore, as both nintedanib and Treprostinil are taught to be administered by inhalation for treating IPF, it would have been prima facie obvious to one of ordinary skill in the art to have administered either or both compositions via a nebulizer, and have had a reasonable expectation of success.
Claim Rejections-Nonstatutory 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 1-3, 5-19, and 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6-11, 13-15, and 17-20 of copending Application No. 19/169921 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims encompass treating the interstitial lung disease, pulmonary fibrosis, by administering a dry powder composition comprising nintedanib and a diketopiperazine. In particular, both sets of claims recite the diketopiperazine as crystalline particles of fumaryl diketopiperazine (see copending claim 8 & instant claim 1); wherein the crystalline particles have overlapping specific surface area ranges (see copending claim 9 & instant claim 10); wherein nintedanib is provided at doses per day that overlap (see instant claim 5 & copending claim 10); and wherein nintedanib is provided in the composition for oral inhalation in a cartridge (see copending claim 15 & instant claim 13). Additionally, both sets of claims recite further administering a prostaglandin analog, including Treprostinil (instant claims 22 & 25, and copending claims 3 & 7). As such, the instant and copending claims are obvious variants of each other and are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 5-19, and 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/210846 (reference application) in view of Wade et. al., WO 2008098196 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims encompass a dry powder composition comprising nintedanib and diketopiperazine particles and a method of treating the interstitial lung disease, pulmonary fibrosis, by administering a dry powder composition comprising nintedanib and diketopiperazine particles. In particular, both sets of claims recite the diketopiperazine as crystalline particles of fumaryl diketopiperazine (see copending claim 4 & instant claim 1); wherein the crystalline particles have the same specific surface area ranges (see copending claim 10 & instant claim 10); wherein nintedanib is provided at doses that overlap (see instant claim 5 & copending claim 12); wherein nintedanib is provided in the composition for oral inhalation in a cartridge (see copending claim 13 & instant claim 13); wherein the dry powder composition has one or more excipients selected from a surfactant, an amino acid, or phospholipid (copending & instant claim 3); wherein the dry powder is amorphous (copending & instant claim 6); and wherein the crystalline particles have a pore size ranging from about 23 nm to about 30 nm (instant & copending claim 11). Instant claims 22-25 differ from the copending claims by reciting further administering a prostaglandin analog, including Treprostinil. However, it would have been prima facie obvious to have added this step to the method of the copending claims. Wade teaches administration of Treprostinil for treating interstitial lung disease such as pulmonary fibrosis and IPF (title & abstract; para [0002-0005], [0010]). Wade teaches Treprostinil can be administered by inhalation in solid or liquid dosage forms (para [0011], [0014], [0035]). Treatment of pulmonary fibrosis and IPF is exemplified (para [0049-0051], [0077-0082]). Wade teaches Treprostinil can be administered in combination with other agents used to treat pulmonary disease (para [0012]). Therefore, it would have been prima facie obvious to have added the step of administering by inhalation a formulation containing Treprostinil, since this formulation is also taught for the treatment of IPF, and have had a reasonable expectation of success.
As such, the instant and copending claims are obvious variants of each other and are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
Prosecution Insights