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
Claims 1-27 are pending and are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/18/2023, 08/29/2024 and 11/24/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This patent application is a U.S. National Phase filing of International Application No. PCT/GB2021/053200, filed on December 7, 2021, which claims the benefit of priority to GB2019335.5, filed on December 8, 2020.
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, 3-4, 7 -8, 10, 12, 18 and 24-25 are rejected under 35 U.S.C. 102 (a) (1) and under 35 U.S.C 102(a)(2) as being anticipated by Page et al. (US 2006/0264490) as evidenced by D’Souza et al. (EXPERT OPINION ON DRUG DELIVERY, 2016 VOL. 13, NO. 9, 1257–127)
Instant claims are drawn to a pharmaceutical composition for oral use comprising as an active substance N- (2-(tert-butyl)-1-((4,4-difluorocyclohexyl)methyl)-1 H-benzimidazol-5-yl)ethanesulfonamide, or a pharmaceutically acceptable salt thereof, and a non-aqueous solvent for the active substance and an immediate release pharmaceutical formulation for oral use comprising the composition
Page et al. discloses instantly claimed compound N- (2-(tert-butyl)-1-((4,4-difluorocyclohexyl)methyl)-1 H-benzimidazol-5-yl)ethanesulfonamide ([0061], claim 5, compound 3, Example 27 [0253-0264]
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Page et al. discloses pharmaceutical compositions of this compound for oral use ([0092-0095], claim 16). They teach that their compositions can also be formulated in solution in aqueous polyethylene glycol solution [0102] and disclose wherein their composition may be in the capsule form [0101].. Page et al. disclose that their inventive compounds exhibit selective activity as agonist of the CB1 receptors and are useful in therapy, especially for relief of various pain conditions such as chronic pain, neuropathic pain, acute pain, cancer pain, pain caused by rheumatoid arthritis, migraine, visceral pain etc. including other disease states in which dysfunction of CB1 receptors is present or implicated [0081-0086]
It is noted and well known in the art that Polyethylene glycol as a solvent disclosed by Page et al. is water soluble. This is evidenced by D’souza et al who discloses that Polyethylene glycol (PEG) has structure flexibility, biocompatibility, amphiphilicity, is devoid of any steric hindrances, and high hydration capacity.. They further disclose that PEG’s may be liquids , semisolids or solids based on their molecular weight and that they play an important role in solubilization and permeation (see page 1260, col.1 , section 1.5 -PEG properties). As such evidentiary documentation explicitly discloses the properties of PEG and the PEG recited by Page et al would therefor inherently possess these properties. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is also noted that, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
In accordance with MPEP §2131.01, it is proper to rely upon a secondary reference for a rejection under 35 U.S.C. 102, provided that the additional reference is relied upon to demonstrate that a characteristic or property not disclosed by the primary reference is, in fact, inherent.
Therefore the composition and method disclosed by Page et al. fully anticipates instant claims 1, 3-4, 7 -8, 10, 12,18 and 24-25.
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 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.
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.
Claims 2, 5-6, 9,11, 13-17, 19-20 and 26-27, are rejected under 35 U.S.C. 103(a) as being unpatentable over by Page et al. (US 2006/0264490) as evidenced by D’Souza et al. (EXPERT OPINION ON DRUG DELIVERY, 2016 VOL. 13, NO. 9, 1257–127) as applied to 1, 3-4, 7 -8, 10, 18 and 24-25 in the 102(b) rejection above, and Goskonda et al. (US 2016/0228405)
The teachings of Page et al. and D’Souza et al. is reiterated below :
Page et al. discloses instantly claimed compound N- (2-(tert-butyl)-1-((4,4-difluorocyclohexyl)methyl)-1 H-benzimidazol-5-yl)ethanesulfonamide ([0061], claim 5, compound 3, Example 27 [0253-0264]
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Page et al. discloses pharmaceutical compositions of this compound for oral use ([0092-0095], claim 16). They teach that their compositions can also be formulated in solution in aqueous polyethylene glycol solution [0102] and disclose wherein their composition may be in the capsule form [0101]. Page et al. disclose that their inventive compounds exhibit selective activity as agonist of the CB1 receptors and are useful in therapy, especially for relief of various pain conditions such as chronic pain, neuropathic pain, acute pain, cancer pain, pain caused by rheumatoid arthritis, migraine, visceral pain etc. including other disease states in which dysfunction of CB1 receptors is present or implicated [0081-0086]
Method of using polyethylene glycols as solvents in pharmaceutical formulations including formulations of cannabinoids is well known in the art as taught by Goskonda et al. Goskonda et al. discloses oral cannabinoid solution comprising water, alcohol and propylene glycol that is stable at room or refrigerated temperatures and possesses an improved in vivo absorption profile, with lower inter-subject variability [0004]. Goskonda et al. discloses formulations comprising a cannabinoid, preferably, and the following ingredients: (i) from about 0 to about 40% water, (ii) from about 15 to about 65% alcohol, preferably ethanol, and (iii) a co-solvent that is (a) propylene glycol from about 0% to about 50%, (b) polyethylene glycol from about 0 to about 50%, and/or (c) a combination of (a) and (b), the solution having a combined total of 100%, wherein the formulations are suitable for oral administration and have in vivo absorption variability of less than 50% [0011]. They disclose polyethylene glycol (PEG) 400 is preferably used in their formulation [0057]. Gooskonda et al. disclose that their formulations of the present invention are useful in treatment and prevention of a very wide range of disorders, including, for example, nausea, vomiting, anorexia and cachexia [0088]
As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Page et al. and Goskonda et al. An ordinarily skilled artisan would be motivated from Page et al. to formulate oral compositions of the instantly claimed compound N- (2-(tert-butyl)-1-((4,4-difluorocyclohexyl)methyl)-1 H-benzimidazol-5-yl)ethanesulfonamide which includes a non-aqueous solvent such as Polyethylene glycol in it. Goskonda et al. further adds to the motivation, that PEG-400 in addition to other non-aqueous solvent such as propylene glycol and water would be a good solvent for formulation of a cannabinoid which is functionally equivalent to the compounds taught by Page et al. It would have been obvious to a person of ordinary skill in the art to substituted the compound taught by Page et al. in place of the cannabinoid suggested by Goskonda et al, thus arriving at the instantly claimed compositions. Substituting equivalents, namely Cannabinoids, motivated by the reasonable expectation that the respective species will behave in a comparable manner or even provide comparable results in related circumstances, see In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) is prima facie obvious. Moreover, the express suggestion to substitute one equivalent for another need not be present to render the substitution obvious, see In re Font 213 USPQ 532.
With regards to instant claims 24-25, The ability of the instantly claimed compound to modulate CB1 receptors and as such its utility in treatment of CB1 receptor implicated disease and conditions was known in the art at the time of this invention. Treatment of anorexia and Cachexia with cannabinoids were also known in the art as taught by Goskonda et al. and such would have been Prima facia obvious to a person of ordinary skill in the art.
With regards to instant claim 20, while Goskonda et al. does not disclose capsule compositions, formulating drugs in the capsule form is an established and well known procedures in pharmaceutical arts and as such it would have been obvious to a person of ordinary skill in the art.
With regards to instant claims 15 and 19, Pharmaceutical industry has well established testing methods for pharmaceutical compositions which has to pass the limitations set forth by the European or US pharmacopeia and this is well known by the persons of ordinary skill in the pharmaceutical art and absence of evidence to the contrary, it would have been obvious to a person of ordinary skill in the art to test and make sure that the developed formulation and composition pass the required standardized tests for dissolution, distribution and stability.
It is noted and well known in the art that Polyethylene glycol as a solvent disclosed by Page et al. is water soluble. This is evidenced by D’souza et al who discloses that Polyethylene glycol (PEG) has structure flexibility, biocompatibility, amphiphilicity, is devoid of any steric hindrances, and high hydration capacity.. They further disclose that PEG’s may be liquids , semisolids or solids based on their molecular weight and that they play an important role in solubilization and permeation (see page 1260, col.1 , section 1.5 -PEG properties). As such evidentiary documentation explicitly discloses the properties of PEG and the PEG recited by Page et al would therefor inherently possess these properties.
With regards to instant claims 13-17, while the references do not specifically disclose the stability of their compositions or the release profile of the active substance or the homogeneous distribution of the active agent in the solvent system, It is noted that the formulation of the instantly claimed compound in the non-aqueous solvent system as instantly claimed would be prima facia obvious to a person of ordinary skill in the art, absence of evidence to the contrary, these functional limitations of the compositions would inherently occur in the formulation It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is also noted that, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in arriving at the instantly claimed pharmaceutical composition absence of evidence to the contrary.
Conclusion
Claims 1-20 and 24-27 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dierdre (Renee) Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/Primary Examiner, Art Unit 1691