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 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.
Previously presented rejection of claim(s) 1, 7-11 rejected under 35 U.S.C. 103 as being unpatentable over Ren, US 9403820 and Ibrahim US 20180207100 is maintained for reasons of record.
Applicant arguments focus on the amendment to base claim 1 which An oral pharmaceutical composition comprising: ART-001 (serabelisib); phosphoric acid; and a hydrophilic polymer, wherein the composition is a granular or powdery dry solid formulation.
Serabelisib is basic because it has an amino group; consequently it forms salt with acids.
The phosphoric acid present in composition of Serabelisib is anticipated to make salts. Salt formation with a variety of acids is taught throughout Ren. See column 3, line 63 for salt formation with phosphoric acid. It is known that Serabelisib, because it is a poorly water-soluble, lipophilic weak base, it exhibits significant pharmacokinetic variability and is strongly impacted by gastric pH and food intake.
As such one of skill in the art would anticipate that formulations of Serabelisib with acid would increase aqueous solubility.
Ren also teaches ‘powder or granules’ as limited by claim 1 at column 21 line 24.
Ren also teaches ‘hydrophilic polymer’ claim 1 at column 24 line 49 onto column 25 line 28.
The rejection is not under Claim Rejections - 35 USC § 102
Therefore the applicants arguments that “The cited references fail to disclose a composition comprising an inorganic salt as claimed”, The references fail to teach or suggest a granular or powdery dry solid formulation, and the Office's assertions regarding "applicant admitted references" are inaccurate’ are not persuasive.
Applicant’s argument include ‘unexpected results’. In this context Applicant points to formulations A-C. These formulations contain other ingredients as well as specific amounts of these in addition of ART-001.. Limitations with respect to these additional ingredients are not found in the claims. While claims are interpreted in light of the specification, limitations are not imported into the claims for obviousness analysis.
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
From previous action:
Ren teaches at column 70 hydrochloric acid salt of Serabelisib (see claim1) and pharmaceutical composition (claim 9). How to make
Serabelisib, is known as INK-1117, MLN-1117, TAK-117 or ART-001 is a well-established, kinase inhibitor. Also see applicant admitted references with regards to pH dependence and oral syrups at page 2.
Claims of Ren corresponds to the inorganic salt limitations of base claim 1 (and that of dependent claims 6, 9, 16).
In column 23 line 52 onto column 24 lines 67 Ren teaches ionic surfactants that correspond to ‘hydrophilic polymer’ limitation of instant claim 1 ( and as specified in claims dependent 7, 10, 14, 17),
Claims 8, 9, 10, 15, 17 of the dependent claims relate to weight ratio of the active ingredient Serabelisib relative to the acid and hydrophilic polymer in the compositions.
At column 20 lines 4 to 67 Ren teaches the amount of active ingredient for the composition. According to Ren, the exact dosage will depend upon the route of administration, the form in which the polymorphs is administered, the subject to be treated, the body weight of the subject to be treated, and the preference and experience of the attending physician. 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. The 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. “[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).
The instant kinase inhibitor Serabelisib is a known BCS class II drug with low solubility and high permeability same as the kinase inhibitor palbociclib. Ibrahim teaches that the solubility of palbociclib depends on pH, see page 1, paragraph [0005] :
Palbociclib is a dibasic compound and has two basic groups with pKa's of approximately 7.3 (the secondary piperazine nitrogen) and 4.1 (the pyridine nitrogen). The solubility of palbociclib free base is pH dependent. Palbociclib is water soluble at low pH (2.1-4.5), while the solubility dramatically decreases as pH rises above 4.5. Palbociclib has poor water solubility (9 μg/mL) at pH 7.9. Concomitant administration of agents which increase gastric pH can alter the solubility and absorption of palbociclib free base formulations.
Though Ren teaches, HCl salt of Serabelisib, one of skill in the art would anticipate, given the low basicity of free base of Serabelisib which has weakly basic nitrogens, by decreasing the pH, increasing the amount of acid would increase the protonation of the nitrogens of Serabelisib, thereby increasing the solubility.
At page 7, [0093]-[0095], Ibrahim teaches how to make pharmaceutical compositions with palbociclib as ingredient and the instantly recited hydrophilic polymers (of instant claims) that has a pH-dependent dissolution profile and is capable of achieving excellent absorption efficiency regardless of the pH in the digestive tract. Also see claims 1-18 at page 18 of Ibrahim.
Each ingredients active (Ren), the acid and inactive hydrophilic polymer (Ibrahim) is known in the art; It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to combine the instant ingredients for their known benefit, that is the why and how ((Ibrahim) since each is well known in the art for their beneficial properties. Again, the invention is a selective combination of the inventions by the prior arts done in a manner obvious to one of ordinary skill in the art. Patent for the combination of known elements wherein their functions remain the same withdraws “what is already known into field of its monopoly and diminishes resources available to skilled men”. Sakraida v. Ag Pro, Inc.189 USPQ 449, 425 US 273, (1976).
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 NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
Prosecution Insights