DETAILED ACTION
Status of the Claims
Claims 1-18 are pending in the instant application. Claims 10-12 and 16-18 have been withdrawn based upon Restriction/Election as discussed below. Claims 1-9 and 13-15 are being examined on the merits in the instant application.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Restriction/Election
Applicant's election without traverse of Group I drawn to compositions of matter, currently claims 1-9 and 13-15, in the reply filed on 06/03/2026 is acknowledged.
The requirement is deemed proper and is therefore made FINAL.
Claims 10-12 and 16-18 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/03/2026.
Priority
The instant Application is a US entry (371) of PCT/KR2021/018637 filed 12/09/2021, and claims priority to KOREA, REPUBLIC OF 10-2021-0155112 filed 11/11/2021.
The U.S. effective filing date has been determined to be 12/09/2021, the filing date of PCT/KR2021/018637. Applicant's claim for a priority date of, 11/11/2021, the filing date of document KR 10-2021-0155112, is acknowledged, however no English translation of this document has been provided such that the examiner can verify written description support of the claims therein. Accordingly, foreign priority to this document is cannot be afforded at this time.
Information Disclosure Statement
The information disclosure statement submitted on 05/10/2024 was filed before the mailing date of the first office action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
Claim Objections
Claims 1-18 are objected to because of the following informalities: The examiner objects to Applicant’s claim numbering, for example, “[Claim 1] (Original):” which is lengthy, and the text of the claim begins on the next line. And for claims 7 and 13 the claim number is on a separate page from the claim text. The examiner suggests removing the brackets and the colon, for example, “1. (original) Microspheres comprising […].” or “claim 1. (Original) Microspheres comprising […].” Appropriate correction is required.
Claim 1 is objected because the claim does not begin with an article such as “A composition of microspheres […].” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 14 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 14 recites the limitation "the disease cause by cholinergic receptor activity disorders" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 15 inherits and also includes the same limitation in lines 1-2, and therefore also lacks proper antecedent basis in the claim. Appropriate clarification is required.
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.
Claims 1-2, 6-8 and 13-15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being clearly anticipated by MALHOTRA (US 2019/0350844 A1; published November 21st, 2019; filed May 15th, 2019).
Applicant Claims
Microspheres comprising varenicline or a pharmaceutically acceptable salt thereof, and a biocompatible polymer (instant claim 1). Applicant further claims the varenicline or a pharmaceutically acceptable salt thereof is contained in an amount of 0.1 to 40% by weight relative to the total weight of the microspheres based on the varenicline free base (instant claim 2). Applicant claims a pharmaceutical composition comprising the microspheres of claim 1, and a pharmaceutically acceptable carrier (instant claim 13) for treatment of a disease caused by cholinergic receptor activity (claim 14), and particularly nicotine dependence and addiction (claim 15).
Disclosure of the Prior Art
MALHOTRA discloses depot formulations including varenicline (abstract, see whole document), and specifically teaches microsphere for prolonged release ([0035] & [0048]). MALHOTRA discloses Example 3 which is an intramuscular (IM) depot injection microspheres composed of varenicline (2-40 % w/w) and biodegradable polymer (PLA, PLGA, PCL)(60-95% w/w)(instant claims 1-2, 6, 13-15). MALHOTRA claims “A pharmaceutical long-acting depot composition comprising a therapeutically effective amount of varenicline, or a pharmaceutically acceptable derivative thereof, and one or more pharmaceutically acceptable excipients.” (claim 1)(instant claim 15). MALHOTRA discloses that: “The depot formulations disclosed herein can deliver a daily therapeutic dose of varenicline for a period of at least 1 week, at least 2 weeks, at least 4 weeks, at least 8 weeks, or at least 12 weeks.” ([0041])(instant claims 7-8). MALHOTRA claims “The long acting sustained release depot pharmaceutical composition according to claim 1, wherein the composition is for use in aid to smoking cessation treatment.” (claim 19)(instant claims 14-15).
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 1-9 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over MALHOTRA (US 2019/0350844 A1; published November 21st, 2019; filed May 15th, 2019) in view of MULLER (US 2018/0147163; published May, 2018) and GU (US 2019/0274955 A1; published September, 2019); and as evidenced by the Merck Index Online entry for Varenicline (Monograph M11395), 2026, 4-pages.
Applicants Claims
Microspheres comprising varenicline or a pharmaceutically acceptable salt thereof, and a biocompatible polymer (instant claim 1). Applicant further claims the varenicline or a pharmaceutically acceptable salt thereof is varenicline pamoate (embonate) salt (instant claims 3-5). Applicant further claims the microspheres are prepared by O/W (oil-in-water) type solvent evaporation or solvent extraction method containing a biocompatible polymer, varenicline pamoate salt, and a dispersion solvent (instant claim 9).
Determination of the scope
and content of the prior art (MPEP 2141.01)
MALHOTRA discloses depot formulations including varenicline, as discussed above and incorporated by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of MALHOTRA is that MALHOTRA does not expressly teach the varenicline salt varenicline pamoate (instant claims 3-5 and 9).
The examiner notes that the commercial produce of varenicline is tartrate salt (Champix™ and Chantix™ Pfizer), which is a white to off-white slightly yellow solid that is highly soluble in water (Merck Merck Index Online entry for Varenicline, p. 2, §§Trademark names and Properties).
MALHOTRA teaches that: “In some embodiments, the pharmaceutical depot composition compositions may comprises any other pharmaceutically acceptable salt of varenicline” ([0039]). MUELLER teaches compositions and their use in methods for treating obesity and related disorders (title, see whole document).
MUELLER teaches that: “in a first aspect, the present invention provides
a composition comprising an agonist of TRPMS (TRPMS-agonist) and an agonist of the nicotinic acetylcholine receptor (nAChR-agonist).” ([0005]). And that: “a pharmaceutical composition, comprising a TRPMS-agonist and an nAChR-agonist for inhibiting weight gain, e.g., weight gain following smoking cessation or for reducing weight.” ([0007]). MUELLER teaches that: “In one embodiment, the nAChR-agonist is 4-(trifluoromethyl)-10-azatricyclo[…]dodeca-2,4,6-triene (CP-601932) or an analogue thereof having the general formula (VI), preferably the general formula (VI'): […].” ([0127]). And that: “Particularly preferred examples of compounds of formula (VI), (VI'), […] include […] and (6R,10S)-7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h]-[3]benzazepine (varenicline, i.e., the compound of formula (VI'), wherein n is 2; the two R9 groups (at positions 4 and 5) join together with the atoms to which they are attached to form pyrazino; and R14 is H).” ([0128], [0143], claim 15). And that: “(ii) the nAChR-agonist is selected from a […]varenicline, […] (including their solvates (e.g., hydrates), salts (in particular, pharmaceutically acceptable salts), […].” ([0230] & [0231]). MUELLER teaches the pharmaceutically acceptable salts include “pamoate (embonate)” ([0182]). It would have been prima facie obvious to select the pamoate (embonate) salt of varenicline, as suggested by MULLER, in the composition of varenicline for prolonged release microspheres of MALHOTRA, as a suitable salt species (MPEP §2144.07).
GU teaches pamoate salts and methods of their use (title, see whole document), and particularly “The composition containing a pamoate salt of donepezil, the method of preparation and the use thereof are disclosed.” (abstract).
GU teaches that: “The most frequently used anion to form a salt of a basic drug is the hydrochloride form. For example, Aricept®, a commercial product of donepezil for oral administration, uses hydrochloride salt. Multiple organic salts of donepezil are also described in U.S. Patent Application Pub. No. 2008/0194628 by Mezei et al. These salts were prepared to improve stability, solubility or increased
dissolution rate for oral administration. They possess desirable properties for immediate release dosage form. However, when extended release delivery of these salts are desired for a prolonged action, extended release technology using rate-controlling polymers are usually required as described in U.S. Patent Application Pub. No. 2011/0218216 […] In addition, such extended release devices tend to be costly to manufacture and difficult to produce at commercial scale. Thus, there still exists a need for improved methods of delivering such agents which maximize the medical benefits of the active agent, can be administered significantly less frequently than the current 24-hour dosing interval and can be produced in a more cost effective manner.” ([0005]). And that: “It is known that the pH of muscle tissue can vary with exercise, stress, and injury which can affect drug solubility, and thus the rate of absorption of injectable drugs. Therefore, it is desirable to find an injectable extended release formulation in which the release rate of the active ingredient is minimally dependent on pH.” (0007).
GU teaches that: “The present invention also relates to the discovery that pamoate salts of donepezil provide a desirable long acting and/or extended release profile.” ([0008]). And that: “In an aspect, the disclosure provides novel pamoate salts of donepezil. […] The above described salts are especially useful in preparing an extended release formulation (or composition) in which the release rate is minimally dependent on the pH of the environment.” ([0009]).
GU teaches that: “It has been discovered that a formulation (or composition)
comprising a pamoate salt of donepezil as an active ingredient or active agent, and one or more pharmaceutically acceptable carriers, can address the long felt need for a stable, pharmaceutically elegant formulation with a controllable release rate which may be useful as a depot formulation or for intramuscular or subcutaneous use.” [emphasis added]([0013]).
GU teaches that: “It has been discovered that the pharmaceutically acceptable salts of donepezil formed using pamoic acid as a counterion surprisingly exhibit very low solubility (Ksp). This low solubility is highly desirable when used in a pharmaceutical composition to provide for extended release of the pamoate salt of donepezil when administered intramuscularly or subcutaneously.” [emphasis added]([0048]).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a long-acting depot pharmaceutical formulation including varenicline PLGA microspheres, as suggested by MALHOTRA, and to utilize the pamoate (embonate) pharmaceutically acceptable salt, as suggested by MULLER, as a suitable species of varenicline salt, the pamoate (embonate) salt being particularly suitable for intramuscular or subcutaneous depot formulations, as suggested by GU, due to the lower water-solubility of the pamoate (embonate) salt.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The examiner cites BRISTOL (US 8,859,622 B1; published October, 2014) as teaching the solubility characteristics of drugs of pamoate salts (see whole document, particularly col. 11, paragraphs 2-3).
Conclusion
Claims 1-9 and 13-15 are pending and have been examined on the merits. Claims 14 and 15 are rejected under 35 U.S.C. 112(b); claims 1-2, 6-8 and 13-15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) and claims 1-9 and 13-15 are rejected under 35 U.S.C. 103. No claims allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IVAN A GREENE whose telephone number is (571)270-5868. The examiner can normally be reached M-F, 8-5 PM PST.
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/IVAN A GREENE/Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
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