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 .
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.
Election/Restrictions
Applicant's election with traverse of Group II (claims 23-29), in the reply filed on 6 October 2025, is acknowledged. The traversal is on the ground(s) that 37 CFR 1.475(b) indicates that products and processes of use of said product are considered to have unity of invention. The Examiner agrees with this traversal and has withdrawn the Restriction Requirement of 5 August 2025.
Applicant's did not provide a compliant species election of “polymer” and “solvent” and “disease” as specifically requested within page 5 of the Election of Species Requirement. Instead, Applicants provided discourse on why they traverse the Election of Species Requirement (focusing on common properties and recognized class of chemical compounds). The Examiner has withdrawn the Election of Species Requirement given Applicants’ traversal of 6 October 2025.
The Restriction Requirement and Election of Species Requirement of 5 August 2025 are each withdrawn.
All claims have been examined on the merits.
Current Status of 18/247,943
This Office Action is responsive to the amended claims of 6 October 2025.
Claims 1-29 have been examined on the merits. Claims 1-2, 12-13, 19-22, and 24 are original. Claims 3-11, 14-18, and 26-29 are previously presented. Claims 23 and 25 are currently amended.
Priority
The effective filing date is 27 October 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 24 July 2023; and 5 April 2023, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 2-11, 13-18, and 24-29 are objected to as these are dependent claims. Dependent claims should begin with -- The -- and not “A” or “An”. Please revise accordingly.
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, and 10-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
AMATERASU (WO 2020/089942 A2, provided by Applicants-and referenced in IDS of 5 April 2023).
The prior art reference AMATERASU teaches a liquid injectable composition (Abstract, “liquid injectable composition”; page 31, Example 4: “Donepezil injectable compositions”) comprising: (a) polymer selected from poly(lactic-co-glycolic acid) (PLGA) (page 31, Example 4, Table 1, Composition 4.2 has 130 mg PLGA; page 10, line 21-22, “release retarding agent includes “polylactide-co-glycolide” and “polylactide”); (b) solvent selected from: N-methyl-2-pyrrolidone (page 31, Example 4 Table 1, Composition 4.2 has 450 mcL or microliters of N-methyl-2-pyrrolidone; page 10, line 34, solvent includes “N-methyl-2-pyrrolidone” and “2-pyrrolidone”, “glycofurol”, “dimethylacetamide”, “propylene glycol”, and “benzyl alcohol”); and c) donepezil (free base), or pharmaceutically acceptable salts thereof (page 17) (page 31, Example 4, Table 1, Composition 4.2 “130 mg of Donepezil base”), and “stabilizing agent” (“Abstract”-hence anticipates instant claim 10). This anticipates instant claims 1 and 6.
Furthermore, AMATERASU teaches the Composition 4.2 liquid injectable composition, from above, having a total volume of 450 mcL (see page 31, Examine 4, Table 1 Composition 4.2, wherein 450 mcL is equivalent to 0.45 mL, which constitutes “up to 3.0 mL”), and hence anticipates instant claim 2.
Moreover, AMATERASU anticipates (a)-(j) of instant claim 11 (see reference claim 25 starting on page 35), which includes “controlled release” [relevant for helping to render obvious claims 19 and 21, below].
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.
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 1-11, 19, 21, and 23-29 are rejected under 35 U.S.C. 103 as being unpatentable over:
AMATERASU (WO 2020/089942 A2, provided by Applicants-and referenced in IDS of 5 April 2023),
in view of:
ANSEL (Ansel, Howard C., et al. “Pharmaceutical Dosage Forms and Drug Delivery Systems.” (1999), 7th ed. Lippincott Williams & Wilkins, pp. 48-53),
and in further view of:
BERGE (Berge, Stephen M. “Pharmaceutical Salts.” J. Pharmaceutical Sciences. (January 1977), Vol. 66, Number 1, pp. 1-19).
The instant claims 1-6, 8-11, 19, 21, and 23-29 are drawn to routinely optimized variables/concentrations in the form of masses, ratios, and weight percentages of donepezil compositions comprising N-methyl-2-pyrrolidone, PLGA, and donepezil active pharmaceutical ingredient. The claims 23-29 are also drawn to methods of use to treat Alzheimer’s disease and Parkinson’s disease and routinely optimized variables/concentrations in the form of varied dosing regimens of said donepezil compositions. Claim 7 is drawn to the HCl salt form of the donepezil composition.
Determining the scope and contents of the prior art:
AMATERASU teaches instant 1-2, 6, and 10-11, see, supra.
Furthermore, AMATERASU teaches use of the donepezil composition 4.2, supra, to treat Alzheimer’s disease and Parkinson’s disease (page 4) thereby helping teaching instant claim 25, wherein the treatment is administered to a human (see page 8-teaches instant claim 24) via intramuscular or subcutaneous administration (see page 8-thereby teaching instant claim 26).
Moreover, AMATERASU teaches that the “retarding agent” (which includes PLGA of Donepezil composition 4.2 from Table 1 of Example 4 (page 31)) is present from 0.01-40 weight percent, which represents a wide range of varying doses/weight percentages (see “C. Release Retarding Agent” on page 10). Moreover, the “solvent” (which includes N-methyl-2-pyrrolidone of the donepezil 4.2 composition from Table 1 of Example 4 (page 31)) also is present within a wide range of varying doses/concentrations: from 5-80 wt % (see page 10). These teachings within this paragraph are useful to help teach/suggest that the artisan would vary the concentrations (weight percentages, etc.) to routinely optimize the treatment efficacy of the donepezil 4.2 (page 31) composition.
Moreover, AMATERASU reference claim 25 starting on page 35 teaches “controlled release” [relevant for helping to render obvious claims 19 and 21, below].
The prior art reference ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48).
BERGE teaches that hydrochloride salt is a well-known FDA approved pharmaceutically acceptable salt (Table 1 on page 2). Artisans mix pharmaceutically acceptable salts, such as hydrochloride (HCl) salts with the active pharmaceutical ingredients (such as donepezil) for the following advantageous reasons: use of pharmaceutically acceptable (HCl) salts help optimize the chemical, biological, physical, and economic characteristics of medicinal agents (ie., donepezil) (see page 1).
Ascertaining the differences between the prior art and the claims at issue:
While AMATERASU teaches instant claims 1-2, 6, and 10-11, see, supra, it does not explicitly teach “a method for treating” “Alzheimer’s disease” and “Parkinson’s disease” by “administering” the donepezil formulation 4.2 (see page 31, Examine 4, Table 1 Composition 4.2). However, AMATERASU does teach that one embodiment of use for the donepezil composition 4.2 is to treat Alzheimer’s disease while another embodiment is to treat Parkinson’s disease (see page 4).
While AMATERASU teaches 0.01-40 weight percent of PLGA and 5-80 wt % of N-methyl-2-pyrrolidone (see page 10), AMATERASU does not explicitly teach the various concentrations (weight percentages and ratios) of claims 3-5, 8-9, 19, 21, and 23.
The prior art reference ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48). However, ANSEL does not teach the specific concentrations and dosing regimens of the instant rejected claims.
While BERGE teaches that hydrochloride salt is a well-known FDA approved pharmaceutically acceptable salt (Table 1 on page 2) and that use of said salts help optimize the chemical, biological, physical, and economic characteristics of medicinal agents (ie., donepezil) (see page 1), the BERGE prior art reference does not teach the limitations of instant claim 1 and others.
Resolving the level of ordinary skill in the pertinent art:
The artisan is knowledgeable in making and using formulations comprising PLGA and polylactide polymers mixed with solvents (such as N-methyl-2-pyrrolidone) mixed with the active pharmaceutical ingredient donepezil, optionally with pharmaceutically acceptable salts such as hydrochloride salt. Furthermore, the artisan is knowledgeable in how to/the need to change the dosage and concentrations thereof to optimize the treatment efficacy of said formulations.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The instant claims are prima facie obvious over the teachings of AMATERASU in view of ANSEL and in further view of BERGE.
The artisan would be expected to use the liquid injectable donepezil 4.2 composition comprising PLGA, N-methyl-2-pyrrolidone, and donepezil (free base), or pharmaceutically acceptable salts thereof (page 17) (page 31, Example 4, Table 1, Composition 4.2) which AMATERASU also teaches can be used to treat Alzheimer’s disease and Parkinson’s disease (see page 4) [interpreted as “a disease or disorder ameliorated by donepezil”] in a method to actually treat Alzheimer’s disease and Parkinson’s disease. The artisan would be motivated to use the liquid injectable donepezil liquid composition 4.2 (page 31 Example 4 Table 1) in a method to treat Parkinson’s disease and Alzheimer’s disease since AMATERASU teaches that donepezil is known to be useful for this purpose (see page 4).
Furthermore, the artisan would be expected to pair/mix the donepezil active pharmaceutical ingredient with HCl salt, since HCl salt is a well-known pharmaceutically acceptable FDA approved commercially marketed salt (see BERGE page 2 Table 1). The artisan would be motivated to mix HCl pharmaceutical salt with donepezil as it permits the artisan to optimize the chemical, biological, physical, and economic characteristics of medicinal agents (ie., donepezil) (see BERGE page 1). This teaches instant claim 7.
Moreover, the artisan would be expected to vary the concentrations of the liquid injectable donepezil 4.2 composition from page 31, including varying the concentrations (such as weight percentages, ratios, and mass) of donepezil active, the PLGA polymer, and the N-methyl-2-pyrrolidone solvent, to maximize treatment efficacy of the donepezil formulation. In fact, AMATERASU permits as much: AMATERASU teaches 0.01-40 weight percent of PLGA and 5-80 wt % of N-methyl-2-pyrrolidone (see page 10). The artisan would also be expected to treat with varied dosing regimens (dosing regimens are interpreted as variables to routinely optimize) to optimize treatment efficacy. The artisan would be motivated to vary the concentrations, above, as the various masses, weight percentages, ratios, and even dosing regimens (all interpreted as “concentrations”) since these are variables routinely optimized in the pharmaceutical arts. This is especially true since neither the claims nor the Specification indicate how the concentrations (doses, weight ratios, weight percentages, and masses) are critical. Moreover, the artisan would look to what is known in the pharmaceutical arts which shows that physicians routinely increase or decrease variables, such as dosage to meet the particular requirements of the patient (see ANSEL page 48).
Moreover, patent law views differences in concentration (herein, the varying ranges of weight percentages/dosing regimens/masses/ratios [mentioned in the rejected claims] of donepezil, PLGA, and N-methyl-2-pyrrolidone) as not supporting 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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); 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."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A).
Thus, prior art reference AMATERASU in view of ANSEL and in further view of BERGE teaches instant claims 1-11, 19, 21, and 23-29.
Claims 1-2, 6, 10-18, 20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over:
AMATERASU (WO 2020/089942 A2, provided by Applicants-and referenced in IDS of 5 April 2023),
in view of:
ZADBUKE (Zadbuke, Nityanand, et.al. “Recent trends and future of pharmaceutical packaging technology.” J. of Pharmacy and Bioallied Sciences. (Apr-June 2013) Vol. 5 Issue 2, pp. 98-110),
and in further view of:
ANSEL (Ansel, Howard C., et al. “Pharmaceutical Dosage Forms and Drug Delivery Systems.” (1999), 7th ed. Lippincott Williams & Wilkins, pp. 48-53).
Claims 12-18, 20, and 22 are drawn to similar limitations as claim 1 but are drafted as “kit” claims.
Determining the scope and contents of the prior art:
AMATERASU teaches instant 1-2, 6, and 10-11, see, supra.
The reference ZADBUKE teaches that injectable pharmaceutical formulations are commonly packaged in prefilled injectable syringes, ampoule, or vials (this is interpreted as a single “unit dosage form”) (see page 99). Due to claim construction (i.e., claim 16 depending from claim 12 “kit”), the combination of AMATERASU and ZADBUKE teach “kit” of the instant rejected claims (see, below).
The prior art reference ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48).
Ascertaining the differences between the prior art and the claims at issue:
While AMATERASU teaches instant claims 1-2, 6, and 10-11, see, above, it does not explicitly teach “kit”, “prefilled injectable syringe”, “ampoule”, or “vial”.
While the reference ZADBUKE teaches that injectable pharmaceutical formulations are commonly packaged in prefilled injectable syringes, ampoule, or vials (this is interpreted as a single “unit dosage form”) (see page 99), it does not explicitly teach what is claimed within instant claims 1-2, 6, and 10-11 (which is part of the “kit” claims this obviousness rejection is rejecting).
The prior art reference ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48). However, ANSEL does not teach the specific concentrations and dosing regimens of the instant rejected claims.
Resolving the level of ordinary skill in the pertinent art:
The artisan is knowledgeable in assembling and packaging pharmaceutical products into kits comprising separate containers such as pre-filled syringes, ampoules, and vials.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would find prima facie obvious the various kit claims of the instant application in light of the teachings of AMATERASU in view of ZADBUKE and in further view of ANSEL.
The artisan would be expected to package the active pharmaceutical ingredient: donepezil with the solvent N-methyl-2-pyrrolidone and the polymer PLGA, at least since the donepezil 4.2 composition is known in the art (see AMATERASU page 31: Example 4 Table 1). The artisan would be expected to package the donepezil, N-methyl-2-pyrrolidone, and PLGA, since it is a liquid injectable and would have to be packaged in some container(s) to reach the physician/pharmacist and be prescribed to the patient in need thereof.
The artisan would be motivated to arrange the liquid injectable donepezil 4.2 composition from AMATERASU, above, into single unit dosage forms comprising any combination of prefilled injectable syringe, ampoule, or vial, since this is known in the prior art (see ZADBUKE page 99). Moreover, the artisan would be expected to arrange the ingredients of the donepezil 4.2 composition as first and/or second containers, wherein the first container comprises donepezil with one of PLGA or N-methyl-2-pyrrolidone, and the second container comprises the other of PLGA or N-methyl-2-pyrrrolidone. The artisan would be motivated to make this decision based on packaging preferences, shelf-life, and ease of access/administration. Thus, this teaches the “kit” claims (at least due to claim construction, since claim 16 depending from claim 12 “kit”), thereby teaching instant claims 12-16.
The Examiner interprets the speed of administration (claim 17) as equivalent to a concentration that the artisan would be expected to routinely optimize. Moreover, the artisan would be expected to routinely optimize the dosing and mixing of the kit contents in order to maximize therapeutic efficacy. The artisan would be motivated to vary the dosing and mixing regimen (interpreted as “concentrations”) since dosing regimens and mixing speeds are variables routinely optimized in the pharmaceutical arts. This is especially true since neither the claims nor the Specification indicate how the dosing regimens and mixing speeds are critical. Moreover, the artisan would look to what is known in the pharmaceutical arts which shows that physicians routinely increase or decrease variables, such as dosage to meet the particular requirements of the patient (see ANSEL page 48).
Moreover, patent law views differences in concentration (herein, the varying dosing regimens and mixing speeds of claim 17) as not supporting the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); 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."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A).
Thus, AMATERASU, in view of ZADBUKE, and in further view of ANSEL teaches instant claims 12-18, 20, and 22. Furthermore, the same obviousness arguments for routinely optimizing other concentrations, such as mass, weight ratios, and weight percentages of the ingredients comprising the donepezil 4.2 composition (page 31 AMATERASU) from the previous obviousness rejection, would flow to this rejection and render prima facie obvious various weight percentages, ratios, and mass of the rejected “kit” claims and ingredients/components/limitations thereof.
Conclusion
No claims are presently allowable as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew D Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625