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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 11, 2026 has been reviewed by the examiner and entered of record in the file.
Claims 1, 6, 10-12, 19, 46 and 48 are amended. Claims 5, 7-9, 13, 14, 20-25, 27, 28, 45, 47 and 49-53 are newly canceled.
Claims 32 and 33, drawn to a method of use, remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, without traverse, there being no allowable generic or linking claim.
Applicant previously made the following species elections: (i) ketamine hydrochloride; and (v) the oxidant butylated hydroxytoluene (BHT). The non-elected species of component (i) remain withdrawn from consideration
Claims 1, 3, 4, 6, 10-12, 15-19, 44, 46 and 48 are under examination with the elected species and are the subject of this office action.
Specification
The disclosure is objected to for the following reasons: The specification recites, “The disclosure provides novel formulations… [language omitted]” in line 1 of the first paragraph, and under “Summary of the Invention” at page 4, line 33, and at page 5, line 16. It is suggested that the term novel be deleted from the language of the specification. Once the determination of the novelty of a claimed invention has been established and the disclosure of the invention made public and/or patented, the claimed invention is no longer novel, since the scope of the invention no longer embraces what is considered “novel.” Thus, the incorporation of “novel” into the language of the specification is not appropriate.
The title of the invention states, “Novel Formulations Comprising Ketamine”, and is therefore objected to for containing “novel,” for the reasons set forth above. Thus, the incorporation of “novel” into the title is not appropriate.
Previous Claim Rejections - 35 USC § 112(b)
9. Claims 19-25, 27, 28, 45, 47, and 49 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
10. Claim 19 was previously rejected as depending from claim 1, and reciting the limitation of “ketamine hydrochloride and one… excipient(s), carrier(s) or diluent(s)”.
In view of Applicant’s amendment to claim 19, in which the limitation of “one or more excipients, carriers, diluents…” is deleted, the previous indefiniteness rejection is withdrawn.
New Claim Rejections - 35 USC § 112(b)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
11. Claims 1, 3, 4, 6, 10-12, 15-19, 44, 46 and 48 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
12. Claims 1 and 10 contain the trademark/trade name Gelucire® 44/14; and claims 16, 17, and 19 contain the trademark/trade name Kelcogel®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name Gelucire® 44/14 is used to identify/describe Lauroyl Polyoxyl-32 glycerides (also known as Lauroyl macrogol-32 glycerides) and the trade name Kelcogel ® is used to identify/describe gellan gum. Accordingly, the identification(s)/description(s) using trademarks are indefinite.
13. Claims 3, 4, 6, 10-12, 15-19, 44, 46 and 48 are rejected as being depending upon and including all of the limitations of rejected claim 1.
Previous Claim Rejections - 35 USC § 103
14. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
15. Claims 1, 3-5, 8, 15-17, 19, 44-48, and 50-52 were previously rejected under 35 U.S.C. 103 as being unpatentable over Mittur et al., WO 2015/051259, in view of Daniely et al., U.S. Pat. No. 9,931,303 B1 (published April 3, 2018), as evidenced by Miyazaki et al., (Journal of Controlled Release 1999).
16. Claims 6, 10, and 18 were previously rejected under 35 U.S.C. 103 as being unpatentable over Mittur et al., WO 2015/051259, in view of Daniely et al., U.S. Pat. No. 9,931,303 B1 (published April 3, 2018), as evidenced by Miyazaki et al., (Journal of Controlled Release 1999), and further in view of Strickley, Robert, Pharmaceutical Research (2004).
17. In view of Applicant’s amendatory changes and cancellations, the previous obviousness rejections have been withdrawn and the following rejections are newly applied, below.
New Claim Rejections - 35 USC § 103
18. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
19. Claims 1, 3, 4, 6, 10-12, 15-19, 44, 46 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Mittur et al., WO 2015/051259, in view of Friedrich et al., WO 2015/173195 A1 (published November 19, 2015),
as evidenced by Miyazaki et al., (Journal of Controlled Release 1999), and further in view of Strickley, Robert, Pharmaceutical Research (2004).
Claim 1, as amended, is drawn to an encapsulated composition formulated for oral administration, comprising:
(i) ketamine or a pharmaceutically acceptable salt or enantiomer thereof, in an amount between 1% and 50% (v/v) (more specifically, 20% (S)-ketamine HCl, (claims 3-4));
(ii) Gelucire 44/14 in an amount between 5% and 70% (v/v);
(iii) PEG1500 in an amount between 1% and 50% (v/v);
(iv) a viscosity modifier in an amount between 20% and 50%, wherein the viscosity modifier is a gum comprising a repeating unit of a tetrasaccharide polymer which consists of two residues of D-glucose and one of each residues of L-rhamnose and D-glucuronic acid;
(v) optionally, an antioxidant; and
wherein the composition is resistant to misuse and/or abuse (claim 44), and
wherein the composition exhibits an immediate release of the ketamine or pharmaceutically acceptable salt or enantiomer thereof (claim 46).
Claim 6 is drawn to claim 1, and limits the PEG1500 to varying concentrations from 1%-50% (v/v %).
Claim 10 is drawn to claim 1, and limits the Gellucire 44/14 concentration to 20.68% (v/v%), 50.55% (v/v%), 55.14% (v/v%) or 59.74% (v/v%).
Claim 15 is drawn to claim 1, and limits the viscosity modifier to a gum material (more specifically, Kelcogel CGHA at a concentration of between 20% and 50% (claims 16 and 17)).
Claim 18 is drawn to claim 1 and limits the antioxidant to BHT.
Claim 19 is drawn to claim 1, and limits the ketamine or pharmaceutically acceptable salt or enantiomer thereof to ketamine HCl, and the viscosity modifier is Kelcogel CGHA.
19. Mittur et al. disclose an oral abuse-deterrent composition in the form of a capsule comprising S-ketamine in Example 8, wherein the ingredients are as follows:
(i) the active agent S-ketamine HCl at a dose of 20% w/w;
(ii) the carrier compounds sorbitan monooleate (SPAN 80), copolymer Copovidone (Kollidon® VA64) and the PEG derivative LABRAFIL M2125CS; and
(iv) the viscosity modifier CARBOPOL® 974P,
(see Example 8, page 32).
19. Mittur et al. teach the advantages of employing viscosity modifiers in composition, (in this case, carbomer), because carbomer is known to gel/ swell when placed in an aqueous environment, thereby forming a viscous substance that significantly reduces and/or inhibits the ability of the drug to be extracted from the dosage form, i.e., acts as an abuse deterrent, (page 8, lines 1-5, and page 9, lines 29-32). Mittur et al. teach that “the material that gels” (i.e., the recited viscosity modifier) should comprise about 1% to about 60% of the abuse deterrent composition (page 10, lines 7-11), which fully embraces the range of from 20% to 50% required by instant claim 1.
20. Mittur et al. disclose additional excipients including non-ionic surfactants, specifically naming the polysorbate Polysorbate 80 (page 14, lines 15-20) as well as poloxamers, copolymers, polyethylene glycols (PEG), triglycerides, and polyglycerides (page 13, lines 5-14, and page 14, lines 4-24. See also page 15, lines 9-11 (solvents including PEG)).
21. Mittur et al. go on to suggest the use of additional gum materials that gel when placed in an aqueous environment and modify viscosity including: guar gum, locust bean gum, and xanthum gum (page 9, lines 32-34 through page 10, lines 1-6), however Mittur et al. do not disclose that the viscosity modifier is a gellan gum comprising a repeating unit of a tetrasaccharide polymer which consists of two residues of D-glucose and one of each residues of L-rhamnose and D-glucuronic acid.
22. As such, Mittur et al. teach an oral abuse-deterrent composition comprising
S-ketamine HCl at a dose of 20% w/w; carrier compounds, the viscosity modifier CARBOPOL® 974P, and suggest polyethylene glycol(s), but do not teach gellan gum or the carrier Gelucire® 44/14.
23. Yet, Friedrich et al. teach a tamper resistant immediate-release formulation for oral delivery in the form of a capsule (page 6, second- sixth paragraphs), comprising the active agent as well as the preferred carrier macrogol-32-glycerol-laurate (i.e., Gelucire® 44/14, page 14, last paragraph-page 15, first line), the preferred viscosity modifier gellan gum (page 15, third and fourth paragraphs), and polyethylene glycol (page 13, seventh paragraph).
24. And, it is clear as evidenced by Miyazaki et al. that gellan gum is commercially available as Gelrite™ or Kelcogel™ and is an anionic deacetylated exocellular polysaccharide secreted by Pseudomonas elodea, with a tetrasaccharide repeating unit of one α-L-rhamnose, one β-D-glucuronic acid and two β-D-glucose residues, which meets the limitation of component (iv) of claim 1 (page 287, left column, last sentence- right column, first sentence).
25. Mittur et al. and Friedrich et al. each teach the use of surfactants, in particular PEGs, but do not explicitly disclose PEG1500.
26. Yet, Palmer et al. teach dosage forms for oral drug delivery in the form of a capsule (paragraph [0044]), wherein the “drug” is any substance that alters the physiology of an animal (paragraph [0045]), wherein the dosage form comprises one or more hydrogel forming excipients in a preferred amount of from 1-50% w/w, specifically naming PEG1500 (paragraph [0102]). Palmer et al. go on to disclose stabilizers including the antioxidant BHT (paragraph [0108]) and disintegrants (viscosity modifiers) including gellan gum (paragraph [0110]).
27. Thus, one skilled in the art would have been motivated to combine the teachings of known tamper resistant immediate-release capsule formulations taught by Mittur et al. and Friedrich et al. and choose gellan gum, Gelucire® 44/14, PEG and optionally Polysorbate 80, from the small genera of commonly employed carriers/ diluents/ excipients in oral drug delivery formulations specifically named, for oral delivery of ketamine, with a reasonable expectation of success. In view of Palmer et al., it would have been obvious to one of skill in the art to additionally select PEG 1500 and the antioxidant BHT to employ in an oral capsule composition comprising S-ketamine HCl to enhance solubility and stability of said composition, with a reasonable expectation of success.
28. And, as stated by the Court in KSR International Co., v. Teleflex Inc., 127 US 1727 (2007), “when a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious” (quoting Sakraida v. AG Pro, Inc., 425 US 273 (1976); see also: Merck v. Biocraft (874 F.2d 804, 807 (Fed. Cir. 1989), indicating that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands; Sundance, Inc. v. DeMonte Fabricated, Ltd., 550 F.3d 1356 (Fed. Cir. 2008): a claimed invention is obvious is it is a combination of known prior art elements that would reasonably have been expected to maintain their respective properties or functions after they had been combined; Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945): indicating that “[r]eading a list and selecting a known component to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle”; Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356 (Fed. Cir. 2012): finding a “strong case of obviousness based on the prior art references of record [wherein the claim] recites a combination of elements that were all known in the prior art, and all that was required to obtain that combination was to substitute one well-known…agent for another”).
As such, claims 1, 3, 4, 15-19, 44, and 46 are prima facie obvious.
Claim 11 is drawn to claim 1, further comprising Polysorbate 80 at between 1% and 30% (v/v%) (more specifically, 4.6% (v/v%), 11.49% (v/v%), or 13.79% (v/v%) (claim 12)).
28. Mittur et al. teach that the amount of non-ionic surfactant is present in an amount of from 0-40 weight percent, based on the total weight of the composition (see page 13, lines 27-31), which fully embraces the concentration range of Polysorbate 80 of from 1%-30%, as required by instant claims 11-12. And, normally it is to be expected that a change in temperature, or in concentration, or both, would be a patentable modification. Under some circumstances, however, changes such as these may impart patentability to a process if the particular changes claimed produce a new and unexpected result which result is different in kind and not merely in degree from the results of the prior art. Such ranges are termed "critical" ranges, and the Applicant has the burden of proving such criticality. However, even if Applicant's modification results in great improvement and utility over the prior art, it may still not be patentable if the modification was within the capabilities of one skilled in the art. More particularly, where 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.
29. Therefore, one of skill in the art would have been motivated to optimize the amount of the carrier compound(s) present (v/v%) in the abuse deterrent immediate release capsule comprising S-ketamine HCl taught by Mittur et al. in view of Daniely et al.
As such, claims 11-12 are prima facie obvious.
Claim 48 is drawn to the composition of claim 1 and limits wherein the dissolution of the ketamine from the composition equates to an 80% recovery of the ketamine after 30-45 minutes.
30. Claim 48 is drafted in terms of an intended outcome which is an inherent property of the composition of claims 1, respectively: “…wherein dissolution of the ketamine or pharmaceutically acceptable salt or enantiomer thereof from the composition equates to an 80% recovery of the active agent after 30-45 minutes.” However, claim 48 is directed to a product (a composition). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). See MPEP 2112.01: Composition, Product, and Apparatus Claims [R-07.2015],
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I. PRODUCT AND APPARATUS CLAIMS — WHEN THE STRUCTURE RECITED IN THE REFERENCE IS SUBSTANTIALLY IDENTICAL TO THAT OF THE CLAIMS, CLAIMED PROPERTIES OR FUNCTIONS ARE PRESUMED TO BE INHERENT.
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31. See also In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971) (Claim 1 was directed to a parachute canopy having concentric circumferential panels radially separated from each other by radially extending tie lines. The panels were separated "such that the critical velocity of each successively larger panel will be less than the critical velocity of the previous panel, whereby said parachute will sequentially open and thus gradually decelerate." The court found that the claim was anticipated by Menget. Menget taught a parachute having three circumferential panels separated by tie lines. The court upheld the rejection finding that applicant had failed to show that Menget did not possess the functional characteristics of the claims.); Northam Warren Corp. v. D. F. Newfield Co., 7 F. Supp. 773, 22 USPQ 313 (E.D.N.Y. 1934) (A patent to a pencil for cleaning fingernails was held invalid because a pencil of the same structure for writing was found in the prior art.).
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As such, claim 48 is prima facie obvious.
Response to Arguments
32. Applicant traverses the obviousness rejection over Mittur et al. in view of Daniely et al., as evidenced by Miyazaki et al. and additionally in view of Strickley et al., and argues the following points:
(i) Applicant argues that while Mittur may be directed to abuse-deterrent and immediate release compositions for various routes of administration, Mittur in fact teaches the skilled person away from oral administration as presently claimed, and instead towards buccal and sublingual administration.
Applicant contends that the inventors have unexpectedly found that the use of gellan gum can provide the desired abuse deterrent properties while also maintaining the rapid release of the ketamine active agent favorable for administration as an oral formulation, in particular, the use of Kelcogel@ CGHA.
33. Applicant's arguments have been fully considered but they are not persuasive. At the outset, it is noted that the Daniely et al. and Strickley et al. references have been dropped from the rejection. Regarding Applicant’s argument that Mittur teaches away from the claimed invention, the examiner refers to MPEP 2141.02 VI, Allied Erecting v. Genesis Attachments, 825 F.3d 1373,1381,119 USPQ2d 1132,1138 (Fed. Cir. 2016) ("Although modification of the movable blades may impede the quick change functionality disclosed by Caterpillar, ‘[a] given course of action often has simultaneous advantages and disadvantages, and this does not necessarily obviate motivation to combine,’" (quoting Medichem, SA. v. Rolabo, S.L., 437 F.3d 1157,1165, 77 USPQ2d 1865,1870 (Fed Cir. 2006) (citation omitted)). Thus, "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed...." In re Fulton, 391 F.3d 1195,1201,73 USPQ2dii4i, 1146 (Fed. Cir. 2004). Mittur’s teaching of allegedly higher bioavailability of the sublingual formulation (Example 7) than the two oral formulations (Examples 8 and 9) does not negate the fact that Mittur specifically discloses an abuse-deterrent capsule formulation for oral administration comprising S-ketamine, at least one carrier and a viscosity modifier.
The newly applied reference Friedrich et al. discloses a tamper resistant immediate-release formulation for oral delivery in the form of a capsule comprising an active agent as well as the preferred carrier macrogol-32-glycerol-laurate (i.e., Gelucire® 44/14, page 14, last paragraph-page 15, first line), and teaches that gums are preferred viscosity modifiers that exhibit tamper resistant properties, specifically naming gellan gum (pages 15 and 16).
As such, nothing unobvious is seen in combining the teachings of Mittur and Friedrich, each directed to tamper resistant immediate release capsule formulations, in order to produce an improved tamper resistant immediate release capsule formulations comprising ketamine, with a reasonable expectation of success.
Conclusion
34. Claims 1, 3, 4, 6, 10-12, 15-19, 32, 33, 44, 46, and 48 are present in the application. Claims 32 and 33 are presently withdrawn from consideration. Claims 1, 3, 4, 6, 10-12, 15-19, 44, 46, and 48 are rejected. No claim is presently allowed.
35. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
