DETAILED ACTION
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 .
Information Disclosure Statement
The information disclosure statement filed on 10/22/2024 is acknowledged and has been considered except where lined through.
Specification
The specification recites numerous trademarks. For example, the use of the term Kollidon®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 15 is objected to because of the following informalities: Claim 15 contains duplicates of Neurofibromatosis Type 1 Associated Plexiform Neurofibromas and low-grade gliomas . Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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) 1-2, 8-15 and 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Warner-Lambert Company (WO02/06213A2) in further view of Gupta et al. (Molecules 2018; 23:1719) and Karagianni et al. (Pharmaceutics 2018; 10: 18).
Warner-Lambert Company teach oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, including crystalline forms, pharmaceutical compositions and method of use thereof (abstract). In particular, Warner-Lambert Company teach crystalline form I and II of N-[(2R)-2,3-dihydroxypropoxyl]-3,4-difluoro-2- [(2-fluoro-4-iodophenyl)amino]benzamide which is the same as the compound referred to in the instant application as Mirdametinib (see page 75, lines 21-30 and for example, Example 39, page 135). Moreover, Warner-Lambert Company teaches pharmaceutical salts of a compound of form I and II, wherein pharmaceutically acceptable salts are known to the skilled artisan and include acid addition salts such as oxalic acid (page 15, lines 8-18). With regards to the pharmaceutical compositions, Warner-Lambert Company teach that compounds, including crystal forms, are formulated prior to administration, wherein the pharmaceutical composition comprises the compound of formula I and a pharmaceutically acceptable carrier and are in the form of a tablet or capsule for oral administration (page 87, lines 16-25). With regards to the method of use, Warner-Lambert Company teach that the compounds of the invention are useful in a method of treating proliferative disorders such as cancer, wherein the cancers include, but are not limited to, brain, breast, non-small cell lung cancer and colorectal cancer (page 85, lines 28-33).
While the prior art teaches crystalline form I and II of N-[(2R)-2,3-dihydroxypropoxyl]-3,4-difluoro-2- [(2-fluoro-4-iodophenyl)amino]benzamide and contemplates a number of acid addition salts, the WO document does not specifically teach an oxalic acid salt form or cocrystal of N-[(2R)-2,3-dihydroxypropoxyl]-3,4-difluoro-2- [(2-fluoro-4-iodophenyl)amino]benzamide.
Gupta et al. teach that specific salts of active pharmaceutical ingredients (APIs) are often formed to achieve desirable formulation properties, wherein the importance of salts is indicated by approximately 50% of the United States Food and Drug Administration (US FDA) approval consisting of APIs in the salt form and half of the top 200 prescription drugs in the United States consist of pharmaceutical salts (page 1 of 15, Introduction).
Karagianni et al. discuss pharmaceutical cocrystals as an alternative approach used to enhance physical properties of pharmaceutical ingredients (page 1, last paragraph). In particular, Karagianni et al. teach that the exact definition of cocrystals and salts in the scientific community are sometimes ambiguous, e.g. escitalopram oxalate, which is considered a 1:1 salt between the base escitalopram and oxalic acid, contains one oxalate dianion and a neutral oxalic acid molecule per two escitalopram cations in the crystal lattice and can behave either as a cocrystal or as a salt (page 5, 1st full paragraph). Moreover, Karagianni et al. teach that changes in relative humidity (RH), in solid forms, must be considered when developing a cocrystal, wherein a systemic study in which caffeine was cocrystallized with various carboxylic acids showed that the cocrystals produced exhibited reduced hygroscopicity compared to the raw API with the caffeine-oxalic acid (2:1) cocrystal exhibiting complete stability to moisture in all RH conditions (page 10 out of 20, (i) Relative Humidity). Similarly, Karagianni et al. teach that the cocrystal of theophylline with oxalic acid showed greater stability than theophylline (page 10 of 30, 3rd full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition taught by Warner-Lambert Company so as to generate an oxalate salt or cocrystal of N-[(2R)-2,3-dihydroxypropoxyl]-3,4-difluoro-2- [(2-fluoro-4-iodophenyl)amino]benzamide an form other solid state forms using the cocrystal in view of the teachings of Gupta et al. and Karagianni et al since applying a known technique such as salt formation or crystallization to a k known compound to yield predictable results such as increased solubility or increased stability at relative humidity. See MPEP 2143(D).
Conclusion
Claims 3-7 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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