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
Status of Claims
Claims 15-34 are pending.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 15-16, 19-21, and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by AB Science (GlobeNewsWire, 11/7/2019, pages 1-6; cited in the IDS filed on 5/25/2022).
AB Science discloses that in a phase 3 study oral mastinib in severe asthma uncontrolled by oral corticosteroids met its primary endpoint (p1, para 1). In particular the effect was significant in two pre-specified patient populations: 1) with severe asthma that were not well controlled by oral corticosteroids at a minimally daily dose greater than 5 mg prednisone and 2) with severe asthma with elevated eosinophilic levels (≥ 0.15 K/µL=150 cells/µL) and not well controlled by oral corticosteroids at a minimally daily dose greater than 5 mg prednisone (p1, para 2-p2, para 1).
AB Science further discloses that mastinib is a new orally administered tyrosine inhibitor that targets mast cells and macrophages and a potent and selective blocker of mast cells and it is well established that mast cells play an important role in asthma, not only in immediate hypersensitivity and in the late inflammation phase but also in tissue remodeling of the airways. (p2, para 3 and p3, para 3).
In addition, AB Science teaches that phase 3 study evaluating the efficacy and safety of masitinib in asthma uncontrolled by high-dose inhaled corticosteroids and with elevated eosinophil level (p3, para 2).
As such, the instant claims are anticipated by AB Science.
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 of this title, 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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 15-34 are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0046063 (hereafter, Moussy) in view of Global initiative for Asthma (GINA, V2.0, April 2019).
Moussy teaches a method of treating severe persistent asthma in human patients, comprising administering a tyrosine kinase inhibitor or mast cell inhibitor such as masitinib or a pharmaceutically acceptable salt thereof (abstract, [0111], and claims 1 and 6).
Moussy discloses clinical trial of masitinib in patients with severe persistent asthma wherein masitinib was orally administered at doses of 3.0, 4.5, and 6.0 mg/kg/day in asthmatic patients with severe persistent asthma (Example 1 and [0120]). The patients were required to have experienced asthma symptoms more than once in 3 days for ≥3 months before screening despite continuous treatment with high-dose inhaled corticosteroids (beclomethasone ≥ 1000 µg or equivalent), long-acting beta2 agonists, and daily oral corticosteroids (OCS) (10 to 50 mg of equivalent prednisolone, with stable dosage for at least 3 months). Thus, the asthma is uncontrolled with inhaled corticosteroid and oral corticosteroid as recited in the instant claim 20-21. Also, the patients have been treated with daily oral corticosteroids (10 to 50 mg of equivalent prednisolone) with stable dosage for at least 3 months, thus the patient received OCSs at an annualized cumulative prednisolone-equivalent OCS dose of at least 900 mg to 4500 mg (10 mg x30 days x3 or 50 x30 days x3) prior to treatment with masitinib, which reads on the instant claim 23-24. In the clinical trial, oral corticosteroid therapy was administered as a first line therapy and masitinib was administered as a second line treatment ([0120] and [0121]).
Moussy teaches the active ingredient masitinib is administered in the form of masitinib mesylate ([0111] and claim 7).
Moussy teaches masitinib is to be administered at a starting daily dose of 3.0 to 6.0 mg/kg/day, daily dose of 4.5 to 6.0 mg/kg/day (claims 8-9) and masitinib is dose escalated by increments of 1.5 mg/kg/day to reach a maximum of 9.0 mg/kg/day (claim 10).
Moussy teaches that masitinib or a pharmaceutically acceptable salt thereof is administered for the treatment of severe persistent asthma in combination with at least one corticosteroid or other controller medication wherein the second controller medication is selected from the group consisting of: high-dose inhaled corticosteroids, oral corticosteroids, anti-IgEs, leukotriene modifiers, long-acting inhaled β2-agonists, or sustained-release theophylline ([0108] and claims 17-18). The anti-IgEs is a biologic recited in the instant claim 32.
In addition, Moussy discloses that masitinib is effective for decreasing eosinophilic airway inflammation and blunting airway hyper-reactivity with acceptable toxicity in experimental feline asthma and teaches that masitinib thus represents a novel treatment with the potential to impact both of these key components of asthma pathogenesis ([0136], [0151], and [0152])
Moussy does not specifically teach that the patient has eosinophilic blood count at baseline equal to or higher than 150 cells/µL, 150 cells/µL to 300 cells/µL, or higher than 300 cells/µL; or the asthma is asthma with type 2 inflammation. Also, Moussy does not specifically teach the combination with IL-5.
However, it was well known in the art that one of phenotypes for severe asthma with type 2 inflammation is blood eosinophil counts being equal to or higher than 150 cells/µL as evidenced by GINA (p10 and P20). GINA further discloses that type 2 inflammation is found in about 50% of people with severe asthma and is characterized by cytokines such as interleukin (IL)-4, IL-5 and IL-13, which are often produced by the adaptive immune system on recognition of allergens (p12-13). GINA further discloses that in severe asthma, type 2 inflammation may be relatively refractory to high dose ICS (p20). Also, GINA recommends that for patients with elevated Type 2 biomarkers despite high dose ICS, non-biologic options should be first considered, given the current high cost of biologic therapy (p22, section 6a). In addition, GINA recommends add-on biologic such as anti-Il-5 agent for patients with severe eosinophilic asthma wherein the patient has equal or higher than 300 cells/µL (p12-13).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use masitinib for severe asthma with elevated baseline eosinophilic blood count (equal to or higher than 150 cells/µL, 150 cells/µL to 300 cells/µL, or higher than 300 cells/µL) because Moussy already teaches and suggests that masitinib is effective for treating severe persistent asthma uncontrolled by OCS and ICS and reducing eosinophilic inflammation. Also, one of ordinary skill in the art would have known that patients with severe refractory asthma uncontrolled by OCS or ICS often have type 2 inflammation which is further characterized with elevated eosinophilic blood count (e.g., ≥ 150 cells/µL, 150 cells/µL to 300 cells/µL, or ≥ 300 cells/µL), and would need add-on treatment as evidenced by GINA. Also, GINA recommeds that for patients with elevated Type 2 biomarkers despite high dose ICS, non-biologic options first should be considered, given the current high cost of biologic therapy. Thus, one of ordinary skill in the art would have been motivated to use masitinib for those patients with eosinophilic severe asthma as add-on treatment on the reasonable expectation that masitinib would be useful for treating severe asthma with elevated baseline eosinophilic blood count via decreasing eosinophilic airway inflammation and blunting airway hyper-reactivity as taught by Moussy. In addition, the skilled artisan would have been motivated to use masitinib in combination with anti-Il-5 agent since Moussy already teaches the combination with other controller medication and anti-Il-5 agent was taught to be useful for treating sever eosinophilic asthma with type 2 inflammation and blood eosinophils ≥300 cells/µL as evidenced GINA.
As to claim 24, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use masitinib for severe asthma with elevated baseline eosinophilic blood count, which is not controlled with biologics because masitinib is taught to be effective for treating severe refractory asthma uncontrolled by OCS and ICS. The skilled artisan would have been to do so on the reasonable expectation that it would be effective for severe eosinophilic asthma not controlled with biologics via its direct inhibitory effects on eosinophilic airway inflammation and airway hyper-reactivity which are key components of asthma pathogenesis as taught by Moussy.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, it is concluded that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 15-34 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of US patent 9078894 as evidenced by Global initiative for Asthma (GINA, V2.0, April 2019).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘894 patent are drawn to a method for the treatment of severe persistent asthma in human patients comprising the step of administering masitinib or a pharmaceutically acceptable salt thereof such as masitinib mesylate at the same daily dose as claimed, wherein the severe persistent asthma is severe persistent corticosteroid-resistant asthma and the compound is administered in combination with at least one corticosteroid or other controller medication such as high-dose inhaled corticosteroids, oral corticosteroids, anti-IgEs, leukotriene modifiers, long-acting inhaled β2-agonists, or sustained-release theophylline.
While the claims of the patent are silent about eosinophil blood count, it was well known in the art that one of phenotypes for severe asthma with type 2 inflammation is blood eosinophil counts being equal to or higher than 150 cells/µL as evidenced by GINA (p10 and P20). GINA further discloses that type 2 inflammation is found om about 50% of people with severe asthma and is characterized by cytokines such as interleukin (IL)-4, IL-5 and IL-13, which are often produced by the adaptive immune system on recognition of allergens (p12-13). GINA also discloses that in severe asthma, type 2 inflammation may be relatively refractory to high dose ICS (p20). GINA recommends that for patients with elevated Type 2 biomarkers despite high dose ICS, non-biologic options should be first considered, given the current high cost of biologic therapy (p22, section 6a). In addition, GINA recommends add-on biologic such as anti-Il-5 agent for patients with severe eosinophilic asthma wherein the patient has equal or higher than 300 cells/µL (p12-13).
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use masitinib for severe asthma with elevated baseline eosinophilic blood count (equal to or higher than 150 cells/µL, 150 cells/µL to 300 cells/µL, or higher than 300 cells/µL) because the claims of the patent already teaches and suggests that masitinib is effective for treating severe persistent corticosteroid-resistant asthma, which is known to have elevated eosinophil count and type 2 inflammation as evidenced by GINA. Thus, one of ordinary skill in the art would have reasonably expected that masitinib would also be useful for treating eosinophilic asthma, which is known to be severe asthma and resistant to OCS or ICS. In addition, the skilled artisan would have been motivated to use masitinib in combination with anti-Il-5 agent since the claims of the patent already teaches the combination with other controller medication and anti-Il-5 agent was taught to be useful for treating sever eosinophilic asthma with type 2 inflammation as evidenced GINA.
As such, the instant claims would have been obvious over the claims of the patent.
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611