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 claims 1-6, 8, 10-13, 15, 17, 23, 25, 28, 30, 33, 37, and 38 rejected under 35 U.S.C. 103 as being unpatentable over Rienhoff US20160237043 and Abraham WO2015170237, Huang US20060089387, Boersen US9884042 and Tran, International Journal of Pharmaceutics 384 (2010) 60–66 and Siepea, International Journal of Pharmaceutics 316 (2006) 14–20 is matained.
Tran and Siepea are added in response to the Remarks.
Applicant’s arguments are considered.
Focusing on the chemical structures and biological properties (receptor level) activity of the cited compounds (active ingredients), Applicant argues that
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This argument misses the rationale underlying the rejection:
The active ingredients, the free base and the salts (including the specific Compound B) of the active ingredient, including the exemplified ditosylate are previously known. The term ‘stabilizer’ just does not render the composition novel and unobvious because these listed additional agents are routinely used in making alternate versions of previously known compositions. The cited references teach this practice in the art. The invention relies on the inherent property of the added acid. On top of this is the fact noted in the previous action that Compound A contains amino groups and therefore expected to make salts with the listed additional agents. Regardless of this commonsense anticipation, the benefit of adding these additional agents to make pharmaceutical compositions is what the references teach. The teachings of Tran and Siepea elaborate more on this.
See Tran, titled
‘The roles of acidifiers in solid dispersions and physical mixtures’
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at page 60, opening statement of Abstract:
Also see Table 3 at column A page 65 and the conclusions at page 65 column B.
Similarly, Siepea also teaches the beneficial properties of using the listed acids in making compositions with optimized property. See page 15 column A Table 1.
The open-ended ‘comprising’ language masks other factors that part of the exemplifications in the disclosure. See Siepea conclusions at page 20 column A in this regard.
As previously noted
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. 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.
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.
Following is from previous action:
Regarding claim 1, Rienhoff teaches pharmaceutical composition comprising: the instant active ingredient, Compound A in Table 1 EX# 158 at page 161 and at page 70 column B. The Table also includes structural analogs of the instantly recited compound and unstable amorphous polymorphs of the compounds. Rienhoff teaches that many different salt forms of unstable polymorph (amorphous form) could be made for optimizing stability for these compounds.
Rienhoff at page 167, section under [0608] First Salt Experiments teach such optimization efforts including for the instant recited acid(s): The free base compound A recited in the claim and the corresponding tosylates (see Rienhoff Figures). Rienhoff does not teach adding specifically recited citric acid, fumaric acid, and tartaric acid to make compositions of compound A See tosylate(s) of Compound A under [0681] and [0691] under Further Characterization of Tosylates Polymorphs onwards for many aspects of the (di)tosylates These disclosures correspond to the active ingredient limitations (more on this later) of claims.
Note that the relevant exemplification of ‘stable composition’ in the instant disclosure focuses on the fumaric acid salt of the active ingredient see dependent claims 37 and 38. More on this later.
The art is replete with examples of making salts of active ingredients of citric acid, fumaric acid, and tartaric acid salts to arrive at stabilized pharmaceutical compositions. For example,
Abraham 2015170237 teaches solid pharmaceutical composition comprising an pharmaceutical formulations of amorphous form solifenacin and a stabilizer selected from the group, tartaric acid, fumaric acid page 5, citric acid at page 3 line 14. The term stabilizer appears multiple times in 2015170237.
Huang US 20060089387 discloses a stabilized pharmaceutical composition comprising an antidiabetic agent and a stabilizer. The preferred stabilizers are selected from the group consisting of ascorbic acid, malic acid, maleic acid, tartaric acid, fumaric acid, citric acid, or combinations thereof. Huang invention also discloses amorphous forms of said antidiabetic agents and a process of preparation thereof, and a method for medical treatment of diabetic mellitus using said pharmaceutical composition. Page 3, column A [009]
Dependent claims 6, 13, (amount of active ingredient) and claims 10-1 (different ‘stabilizer’ acids), claims 13, 15 (amount of stabilizer), claims 17, 23 (amount of filler), claim 25 (disintegrant), claim 26 (amount of disintegrant)., claim 30 (lubricant), claim 33 (amount of lubricant), claims 37 and 38 (specific amounts of components, more on this later).
Rienhoff teachings includes fillers such as lactose [0273] in disintegrants [0288] and lubricant [0273]. These are routinely used conventional agents and methods of optimizing these are well-known and routine in the art. More specific as to other such inactive ingredients (crospovidone, magnesium stearate, avicel) in Tables in instant claims 37 and 38, see claims 5, 9, 11 and 12 of US 9884042. Also see https://shms-prod.s3.amazonaws.com/media/editor/147459/L3_Pharmaceutical_Excipients__Types_of_Tablets.pdf.
As to the amounts of compound A and acid (fumaric) in claim 37 and 38: Weight equivalents are used here. Use of molar equivalent fumaric acid would be same as using fumarate salt of compound A and the amount of fumaric acid would be less than the indicated weight equivalent because of the lower molecular weight of fumaric acid. There is nothing in the specification such as comparative data, as to the benefit of using excess fumaric acid, that is more than formation of fumaric acid salt for secondary considerations.
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). 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).
All the claimed elements active and inactive ingredients were known in the prior art, one of skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions to arrive at the instantly claimed composition. Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art.
As such nothing unobvious is seen in the claims.
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.
Claim(s) 1-6, 8, 10-13, 15, 17, 23, 25, 28, 30, 33, 37, and 38 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. US 9981922 further in view of Rienhoff US20160237043 and Abraham WO2015170237, Huang US20060089387, Boersen US9884042 and Tran, International Journal of Pharmaceutics 384 (2010) 60–66 and Siepea, International Journal of Pharmaceutics 316 (2006) 14–20 is matained.
Applicants argument are not persuasive. Applicant points to her/his discussions under 103.
For the same rationale explained above under Claim Rejections - 35 USC § 103. Applicant’s argument are not persuasive.
Following is from previous action:
Claims of 9981922 compound pharmaceutical composition of instantly recited compound A and bistosylate salt of compound A of instant claim 1. The claims of 9981922 are silent with respect to limitation with respect to ‘at least’ part of the instant base claim 1 limitation.
The active ingredient in the composition of claims of 9981922 and the ‘at least’ limitation absent in instant base claim and the instant dependent claim limitations are previously known as pointed out below: The teachings of Rienhoff, Abraham and Abraham shown below are invoked to the deficiency in claims of 9981922.
Rienhoff teaches the pharmaceutical composition comprising: the instant active ingredient of claims of conflicting claims, Compound A in Table 1 EX# 158 at page 161 and at page 70 column B. The Table also includes structural analogs of the instantly recited compound. Rienhoff teaches that many different salt forms of unstable polymorph (amorphous form) could be made for optimizing stability for these compounds.
Rienhoff at page 167, section under [0608] First Salt Experiments teach such optimization efforts including for the instant recited acid(s) salts. In addition to the free base recited in the claim and the corresponding tosylates (see Rienhoff Figures), Rienhoff does not teach adding specifically recited citric acid, fumaric acid, and tartaric acid to make compositions of compound A Also see tosylate(s) of Compound A under [0681] Tosylated and [0691] under Further Characterization of Tosylates Polymorphs onwards many aspects of the (di)tosylates These disclosures correspond to the active ingredient limitations (more on this later) of claims.
Abraham 2015170237 teaches solid pharmaceutical composition comprising an pharmaceutical formulations of amorphous form solifenacin and a stabilizer selected from the group, tartaric acid, fumaric acid page 5, citric acid at page 3 line 14. The term stabilizer appears multiple times in 2015170237.
Huang US 20060089387 discloses a stabilized pharmaceutical composition comprising an antidiabetic agent and a stabilizer. The preferred stabilizers are selected from the group consisting of ascorbic acid, malic acid, maleic acid, tartaric acid, fumaric acid, citric acid, or combinations thereof. Huang invention also discloses amorphous forms of said antidiabetic agents and a process of preparation thereof, and a method for medical treatment of diabetic mellitus using said pharmaceutical composition. Page 3, column A [009]
Compound A and acids to make salts , filler, disintegrant, lubricant are conventional routinely used inactive ingredients in pharmaceutical art. Rienhoff teachings includes fillers such as lactose [0273] in disintegrants [0288] and lubricant [0273]. These are routinely used conventional agents and methods of optimizing these are well-known and routine in the art. More specific as to other such inactive ingredients (crospovidone, magnesium stearate, avicel) in Tables in instant claims 37 and 38, see claims 5, 9, 11 and 12 of US 9884042.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32 (2010) 324–330.
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.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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