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 . Claims included in prosecution are claims 1 and 3-13.
Previous Rejections
Applicants' arguments, filed 8/15/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103 (Maintained)
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.
1. Claims 1, 3-6 and 8-13 are rejected under 35 U.S.C. 103 as being unpatentable over Kandula (WO 2019/186357, Oct. 3, 2019) (hereinafter Kandula).
Kandula teaches pharmaceutical compositions comprising compounds of formula I or intermediates thereof and one or more of pharmaceutically acceptable excipients and/or pharmaceutically acceptable carriers, wherein formula I represents ketamine and RH comprises acids such as pamoic acid (¶ [0008]).
PNG
media_image1.png
297
280
media_image1.png
Greyscale
In the compound of formula I, the ketamine moiety can exist as R enantiomer, S enantiomer or a mixture thereof in equal proportions and one of the enantiomer could be selected for the salt preparation process (satisfies active of claim 1) (¶ [0010]). The pharmaceutical composition comprising the compound of formula I is formulated as a dosage form such as intramuscular and sustained release (satisfies forms of claim 1 & 12) (¶ [0018]). Suitable pharmaceutically acceptable excipients include wetting agents and buffering agents (satisfies claim 9) (¶ [0030]). Suitable pharmaceutically acceptable carriers include sodium carboxymethyl cellulose, propylene glycol, glycerin (satisfies carrier of claim 1, 3, 5, & 8) (¶ [0031]). The composition may utilize nanoparticles in drug delivery (¶ [0055]). The pharmaceutical compositions can be formulated by combining the compositions and the pharmaceutically acceptable excipient and/or carriers in the form of injectable solutions (satisfies form of claim 7) (¶ [0056]). The active ingredient can be presented in the pharmaceutical compositions for parenteral use in a concentration of from about 0.05 to about 50% w/v (satisfies claim 10-11) (¶ [0062]). Suitable carriers include lubricants such as steric acid (satisfies carrier of claim 6) and antioxidants such as lactic acid (¶ [0065, 0067, &, 0069]).
The prior art is not anticipatory insofar as this combination must be selected from different lists/locations in the reference. It would have been obvious, however, to have made a sustained release pharmaceutical composition comprising a ketamine pamoate salt along with pharmaceutically acceptable carrier and excipients, as instantly claimed, since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP § 2143 (I)(A).
Regarding the particle size recited in instant claim (i.e., (d50) of less than 20 microns), as discussed above, Kandula discloses wherein the composition may utilize nanoparticles in its drug delivery mechanism. As such, since Kandula discloses the use of nanoparticles and nanoparticles have a particle size of less than 100 nm (i.e., 0.1 micron), it would reasonable for one of ordinary skill in the art to conclude that Kandula’s particles would have average particle sizes that encompass the d(50) values recited in the instant claim.
Regarding the specific surface area recited in instant claim 4 (i.e., 300 m2/g) and resistance to heat recited in instant claim 13, specific surface area and heat resistance are descriptive and thus would be properties of the claimed product. Kandula discloses substantially the same composition comprising substantially the same actives, pharmaceutically acceptable carriers, and pharmaceutically acceptable excipients. Kandula further discloses a particle size encompassed by the instant claims and substantially the same administration methods. Therefore, it would reasonable for one of ordinary skill in the art to conclude that the particles/product of Kandula would have substantially the same specific surface area and heat resistance as the particle/product of the instant claims.
Response to Arguments
Regarding allegations of unexpected results, an affidavit or declaration must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. See MPEP § 716.02(e).
Applicant does not appear to have compared their compositions to the closest prior art. As such, one of ordinary skill in the art cannot appreciate the significance of the data presented. Absent a direct comparison with a comparative formulation, it is unclear if the alleged improvement is indeed a surprising and unexpected change or if these results fall within the range of expected outcomes in the art, and a meaningful assessment cannot be made.
Furthermore, Applicant has the burden of explaining the data in any declaration they proffer as evidence of non-obviousness. MPEP § 716.02(b)(II).
Applicant has not adequately explained the results. For instance, it is entirely unclear what aspect of Applicant’s formulation is critical and how this criticality is reflected in the data. Without Applicant clarifying which feature is critical and why it is critical, it is difficult for one of ordinary skill in the art to understand and evaluate the invention’s contribution over the prior art.
Moreover, any differences between the claimed invention and the prior art may be expected to result in some difference in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. The burden is on applicant to establish that the results are in fact really unexpected and of statistical and practical significance. Ex parte Gelles, 22 USPQ2d 1318 (Bd. Pat. App. & Inter. 1992). See also MPEP § 716.02.
Applicant does not appear to have discussed same with respect to objective data. For example, Applicant pointed to Example 17 demonstrating that utilizing the instant invention’s formulations can lead to increased drug loading. The instant specification makes no mention of any increased drug loading and does not appear to establish that results relating to this are unexpected. Furthermore, when looking to the pharmacokinetic performance of the solutions obtained in Example 17, SL01, an example with less “drug loading”, performed just as well as, if not better than, SL03, an example with higher “drug loading”, in the average plasma concentration in rats as well as ketamine release percentages. SL02, another example with less “drug loading”, outperformed SL03 in the average plasma concentration in rats as well as ketamine release percentages since it had a release time of 14 days instead of 10 days. As such, it is unclear if Applicant’s finding that “using the specific pharmaceutically acceptable carrier as recited in the independent claim 1, and the specific excipient as recited in claim 6” is indeed advantageous or unexpected.
Applicant also points to Example 18 and the particle sizes achieved. It is unclear if said particle sizes are the result of “using the specific pharmaceutically acceptable carrier claimed” or if they are the result of the milling processes the compositions were subjected to.
Regarding Example 24, since Applicant did not also test R,S, R, or S, Ketamine HCL, it is unclear if the alleged improvement in immobility and sedation is due to the use of the enantiomers of ketamine or due to the use of the pamoate salt, and/or if the effect is additive or synergistic.
Finally, assuming purely arguendo that unexpected results have been established, the probative value of the evidence as compared to the invention as claimed must then be determined, i.e., the claims must be “commensurate in scope” with the showing. MPEP § 716.02(d). See also MPEP § 2145. Applicant must explain the “manner in which the specific compositions illustrated are considered to be commensurate in scope with the claimed invention”; see Ex parte Gelles, 22 USPQ2d 1318 (Bd. Pat. App. & Inter. 1992); see also MPEP 716.02, citing same.
For instance, Applicant’s claim 1 requires the presence of any one of 20 carriers. However, the examples tested for pharmacokinetics, releasability, stability, etc. (i.e., SL01-SL04, AS01-AS07, & AS11) only contained 6 of said 20 carriers (i.e., NaCMC/NaCL, DMAc, NMP, & PEG4000/Tween 80). Furthermore, some example contained palmitic acid which is not required by instant claim 1 at all. As such, it is unclear if only using the carriers tested would result in the alleged unexpected results or if using all carriers encompassed by the instant claims would as well. Further, it is not clear if the results would vary if other carriers were used in place of the ones tested. In order for this to be established, the tested carriers must be reasonably representative of pharmaceutical carriers in general. However, no evidence of this has been provided. As such, Applicant’s data is not commensurate in scope with the instant claims.
Regarding Applicant’s argument that Kandula teaches the use of different acids, and provides no motivation for using pamoic acid as the RH group, the Examiner submits that a reference is relied upon for all it teaches and suggests, even non-preferred embodiments. See MPEP § 2141.02 (VI). Although the acids disclosed by Kandula have divergent properties, Kandula specifically teaches pamoic acid as a suitable acid for use as the RH group. Furthermore, Kandula goes on to claim pamoic acid as one of the possible acids for use as the RH group (Ref. Claim 1). Therefore, one would be motivated to use pamoic acid in the composition of Kandula because Kandula discloses the use of this acid and goes on to claim the use of this acid as well. Accordingly, it would have been reasonable for one of ordinary skill in the art to have formulated Kandula’s compounds of formula I to comprise pamoic acid as the RH group since Kandula teaches this acid to be suitable for use with this compound.
Regarding Applicant’s arguments about Kandula’s teaching of “hydrobromic acid”, the Examiner points out that this acid is listed among other suitable acids for use as the RH group. Kandula does not designate hydrobromic acid as a preferred acid nor is it used in an example. Hydrobromic acid is not reasonably representative of all the acids that Kandula discloses. Furthermore, one of ordinary skill in the art would recognize that there are chemical differences between hydrobromic acid and hydrochloric acid. Consequently, one of ordinary skill in the art would appreciate that it is not reasonable for one to draw a generic conclusion that the instant compositions outperform those of Kandula. Nonetheless, Kandula does disclose that suitable acids for use as the RH group include pamoic acid. As such, one of ordinary skill in the art would have had a reasonable expectation of success when formulating Kandula’s ketamine composition to comprise pamoic acid as the RH group since it is suitable for use as taught by Kandula.
In light of the foregoing, the Examiner does not find Applicant’s arguments to be persuasive and the rejection is maintained.
2. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kandula (WO 2019/186357, Oct. 3, 2019) (hereinafter Kandula) in view of Tyler et al. ((Advanced Drug Delivery Rev., 2016) (hereinafter Tyler).
Kandula is discussed above and differs from the instant claims insofar as it does not disclose polylactic acid as a carrier.
Tyler disclose polylactic acid (PLA) and its copolymers a long history of safety in humans and an extensive range of applications. PLA is biocompatible, biodegradable by hydrolysis and enzymatic activity, has a large range of mechanical and physical properties that can be engineered appropriately to suit multiple applications, and has low immunogenicity. Formulations containing PLA have also been Food and Drug Administration (FDA)-approved for multiple applications making PLA suitable for expedited clinical translatability. These biomaterials can be fashioned drug delivery systems. PLA's application as drug-loaded nanoparticles drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities (Abstract).
It would have been obvious to one of ordinary skill in the art prior to filing the instant application to have used polylactic acid as a carrier for the drug delivery systems of Kandula motivated by the desire to use a carrier that is biocompatible, has low immunogenicity and can be used as a drug-loaded nanoparticle drug carrier as disclosed by Tyler.
Response to Arguments
Applicant argues that due to the unpredictability of pharmaceutical compositions one of ordinary skill in the art would not be motivated by to combine Kandula and Tyler to use polylactic acid.
The Examiner does not find these arguments persuasive.
The Examiner submits that obviousness does not require absolute predictability, and conclusive proof of efficacy is not required to show a reasonable expectation of success. . See MPEP § 2143.02. Tyler provides strong motivation where they disclose that PLA is biocompatible, has low immunogenicity and can be used as a drug-loaded nanoparticle drug carrier. Furthermore, Tyler does not teach away from using PLA in ketamine compositions. As such, in light of the Tyler disclosure, one of ordinary skill in the art would have been motivated to formulate Kandula’s composition to comprise PLA as part of routine optimization with a reasonable expectation of success.
In light of the foregoing, the Examiner does not find Applicant’s arguments to be persuasive and the rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
1. Claims 1 and 3-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,981,617 B2 (hereinafter ‘617).
Although the claims at issue are not identical, they are not patentably distinct from each other because they both disclose a ketamine pamoate salt having a stoichiometry of 2:1 of ketamine to pamoate and a pharmaceutical composition comprising the same. The difference between the instant claims and the ‘617 claims lies in the fact that the instant claims recite a “sustained release pharmaceutical composition” comprising the compound of the patented claims. As such, it would have been obvious for one of ordinary skill in the art to have used the ketamine pamoate salt of ‘671 in the sustained release pharmaceutical composition of the instant claim since it is the same active recited in the instant claims.
Response to Arguments
Applicant requested that the double patenting rejections recited above be held in abeyance until otherwise allowable subject matter is identified. Accordingly, the rejections are maintained.
Conclusion
Claims 1 and 3-13 are rejected.
No claims are 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 Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
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, Frederick Krass can be reached on (571) 272-0580. 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.
/A.A./Examiner, Art Unit 1612
/FREDERICK F KRASS/Supervisory Patent Examiner, Art Unit 1612