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 .
Priority
This application is a 371 of PCT/IB2021/054076 05/13/2021 with a claim to foreign priority to INDIA 201941053406 (05/23/2020).
Status
Any rejection not reiterated in this action is withdrawn.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nagane et al. (US20180028662).
Nagane teaches compositions comprising lenvatinib mesylate (9.8 mg/mL) and calcium hydroxide (0.97 mg/mL) (i.e. Ex 34 in Table 18; [0064]-[0067]) where calcium hydroxide is a excipient stabilizing agent and anticipates the claim 1 and 2. Regarding claim 9, the compositions when prepared as per Test Example 2 ([0037]-[0043]), the resulting composition would inherently have a pH of between about 5.0 and 14.0 and anticipate the claim.
Response to Remarks - Claim Rejections - 35 USC § 102
Applicant argues that Nagane requires preparation of a suspension or solution and thus does not anticipate the instant claims to an “oral liquid suspension formulation”. This argument is not persuasive as Nagane clearly teaches all elements of the claim including an oral liquid suspension for example Ex 34. The rejection is maintained.
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.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Nagane et al. (US20180028662) in view of Strickley et al. (Pharmaceutical Research, Vol. 21, No. 2, February 2004, p. 201-230).
Nagane teaches the liquid pharmaceutical compositions as detailed in the 35 USC 102 rejection above and incorporated herein which also renders the claims obvious under 35 USC 103. Nagane also describes the motivation for optimization of the formulation to, inter alia, reduce bitterness ([0011]: “The present inventors have found that Compound 1 or a pharmaceutically acceptable salt thereof has bitterness. As a result of earnest studies, the present inventors have found that the bitterness of Compound 1 or the pharmaceutically acceptable salt thereof can be suppressed by mixing a basic substance such as calcium carbonate with Compound 1 or the pharmaceutically acceptable salt thereof.”). Nagane described numerous experimental optimizations of the various excipients to reduce bitterness and improve pharmaceutical characteristics of the composition in the Examples ([0034]-[0133]).
Regarding claim 3, Nagane teaches carmellose (a.k.a. carboxymethylcellulose) calcium corresponding to the claim’s element (a).
Regarding claim 3’s (d) stabilizing agent, Nagane teaches hydroxides of calcium (0.97 mg/mL) and sodium (i.e. Ex 34 in Table 18; [0064]-[0067]) as well as basic hydroxides ([0026]).
Regarding claim 3’s (e) sweetener and (g) flavoring agent, Nagane teaches formulation with sucrose and apple juice ([0033]). Regarding claim 3’s element (i) of purified water, Nagane teaches forming aqueous solutions in Test Example 2 ([0037]-[0043]).
Nagane does not specifically teach claim 3’s element of (b) wetting agent (polysorbate) and (c) organic co-solvent (polyethylene glycol).
Strickley teaches oral solution formulations including polysorbate and polyethylene glycol (p. 208: “Most over-the-counter oral solution formulations contain polyethylene glycol, propylene glycol, and/or glycerin whereas a few products contain polysorbate 20 and/or poloxamer 407”).
Nagane does not specifically teaches claim 3’s element of (f) antioxidant.
Strickley teaches the use of the antioxidant BHT in oral formulations (p. 212).
Nagane does not specifically teaches claim 3’s element of (h) buffering agent.
Strickley teaches use of buffers oral formulations (p. 208).
Regarding claim 4’s suspending agent, Nagane teaches carmellose (a.k.a. carboxymethylcellulose) calcium and crystalline cellulose which service the same purpose.
Regarding claim 5’s wetting agent, Strickley teaches oral solution formulations including polysorbate and polyethylene glycol (p. 208: “Most over-the-counter oral solution formulations contain polyethylene glycol, propylene glycol, and/or glycerin whereas a few products contain polysorbate 20 and/or poloxamer 407”).
Regarding claim 6’s stabilizing agent, Nagane teaches hydroxides of calcium (0.97 mg/mL) and sodium (i.e. Ex 34 in Table 18; [0064]-[0067]) as well as basic hydroxides ([0026]) which one of skill in the art would at once envisage potassium as being a member of the known hydroxides.
Regarding claim 7’s cosolvent, Strickley teaches oral solution formulations including polyethylene glycol (p. 208: “Most over-the-counter oral solution formulations contain polyethylene glycol, propylene glycol, and/or glycerin whereas a few products contain polysorbate 20 and/or poloxamer 407”).
Regarding claim 8, as with claims 1, 4, and 5, the combination of Nagane and Strickley teach the elements.
Regarding claim 9, as with claim 1 Nagane teach a composition that would inherently be at the claimed pH range.
In regards to each of the above claims, the level of ordinary skill in the art of pharmaceutical formulation is very high and one of ordinary skill in the art would routinely consider alternative formulations and optimizing excipients, including their amounts to improve efficacy and stability as routine optimization as suggested by both Nagane ([0033]: “The pharmaceutical composition of the present invention can be produced by any of known methods such as methods described in The Japanese Pharmacopoeia, Sixteenth Edition, General Rules for Preparations”) and Strickley (p. 201-202). The combined teaching of Nagane and Strickley would predictably guide one of ordinary skill in the art to the claimed invention with a reasonable expectation of success. Furthermore, the prior art combination is suggested by the same field of endeavor where one of ordinary skill in the art would consider such optimizations for the purpose of improving the properties of efficacy and stability to important and optimizable factors in every pharmaceutical preparation. One of ordinary skill in the art would considered optimization of the same properties in considering the amounts of each of the excipients which would have also been predictable. “[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); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”); MPEP 2144.05. Thus, the claims are obvious.
Response to Remarks - Claim Rejections - 35 USC § 103
Applicant argues similarly as with the 35 USC 102 rejection and further that an absence of “lumps”, storage stability, pourability, etc. distinguish the prior art over the claims. The instant claims do not include limitations for any of these properties and thus does not distinguish the prior art from the claims. Applicant also argues that the combined teaching of the prior art would not enable one of skill in the art to form the invention as claimed, including the absence of “lumps”, etc. This is not persuasive because the level of skill is very high as evidenced by the teaching of Nagane and Strickley such that one of ordinary skill in the art would consider forming a liquid pharmaceutical suspension routine and well within their technical grasp. Thus, the rejection is maintained.
Conclusion
No claims allowed.
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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626