DETAILED ACTION
Response to Amendment
Applicant’s amendment and response, submitted January 29, 2025, has been reviewed by the examiner and entered of record in the file. Claims 1, 3-15, 19, 25, 27, 46 and 47 are amended. Claims 2, 26, 29-31, 42, and 43 are canceled. Claims 51-53 are newly added.
Applicant previously made the following species elections: (a) ketamine hydrochloride; (b) Gelucire 44/14; (c) a gum comprising a repeating unit of the tetrasaccharide polymer which consists of two residues of D-glucose and one of each residues of L-rhamnose and D-glucoronic acid; and (d) butylated hydroxytoluene (BHT).
Claims 32 and 33, drawn to a method of use, remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The non-elected species of component (i) also remain withdrawn from consideration, i.e., agents comprising ketamine compounds other than ketamine HCl, racemic ketamine HCl, (R)-ketamine HCl, or (S)-ketamine HCl.
Claims 1, 3-25, 27, 28, 44-53 are under examination with the elected species and are the subject of this office action.
Previous Claim Rejections - 35 USC § 112(a)
6. Claims 1-19 and 42-50 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
7. In view of Applicant’s amendatory changes to claim 1 to limit the components (i)-(iii) of claim 1 and delete the recitation of enantiomers, derivatives or metabolites thereof, the previous 35 U.S.C. 112(a) rejection for lack of written description is withdrawn.
Previous Claim Rejections - 35 USC § 112(b)
8. Claims 1-31 and 42-50 were previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite regarding the recitation of plurals.
9. In view of Applicant’s amendatory changes to claim 1 to replace the recitation of “salts, enantiomers, derivatives or metabolites thereof,” with the clause “a pharmaceutically acceptable salt or an enantiomer thereof,” the previous 35 U.S.C. 112(b) rejection for indefiniteness is withdrawn.
10. Claim 5 was previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for reciting a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim).
11. In view of Applicant’s amendment to delete “(viii) poloxamer 124,” “(ix) polysorbate 80,” “(x) polysorbate 20,” “(xiii) Polyethylene glycol 1000,” “(xiv) Polyethylene glycol 1500,” “(xv) Polyethylene glycol 2000,” “(xvi) Polyethylene glycol 6000,” “(xvii) Polyethylene glycol 8000,” “(xviii) Kolliphor HS15,” “(xix) Gelucire 44/14,” “(xx) Gelucire 48/16,” and “(xxi) Gelucire 50/13” from the claim, the previous indefiniteness rejection is withdrawn.
Previous Claim Rejections - 35 USC § 102
12. Claims 1-5, 42, 44, 46, 48 and 50 were previously rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Mittur et al., WO 2015/051259.
13. In view of Applicant’s amendatory changes to limit the viscosity modifier (iii) of claim 1, the previous anticipatory rejection is overcome and is withdrawn.
14. Claim 19 was previously rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ford, Peter, U.S. 6,461,600 B1.
15. In view of Applicant’s amendment to change the dependency of claim 19 to claim 1, the previous anticipation rejection is withdrawn.
Previous Claim Rejections - 35 USC § 103
16. Claims 6-31, 43, 45, 47 and 49 were previously rejected under 35 U.S.C. 103 as being obvious over Mittur et al., WO 2015/051259, and further in view of Strickley, Robert, Pharmaceutical Research 2004.
17. In view of Applicant’s amendatory changes, the previous obviousness rejections are withdrawn. However, in consideration of said amendments, a new ground of rejection is made (see below).
New Claim Rejections - 35 USC § 112
18. 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.
19. 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.
20. Claim 19 is drawn to claim 1, and further limits the composition: “comprising ketamine hydrochloride and one or more excipients, carriers or diluents, selected from the group consisting of:,” wherein several carriers, viscosity modifiers and antioxidants are recited, [emphasis added], which is confusing. Independent claim 1 recites an encapsulated composition requiring (i) the active agent (ketamine HCl); (ii) one or more carrier compound(s); and (iii) a viscosity modifier. Therefore, there is insufficient antecedent basis for the recitation of “ketamine hydrochloride and one… excipient(s), carrier(s) or diluent(s)”.
In view of a broadest reasonable interpretation, the recitation of “[t]he composition of claim 1, comprising ketamine hydrochloride and one or more excipients, carriers or diluents,” is construed to mean, “the composition of claim 1 comprising ketamine hydrochloride, and wherein the excipients, carriers, and/or diluents are selected from the group consisting of:”.
21. Claims 20-25, 27, 28, 45, 47 are 49 are dependent upon claim 19 and thus include the limitation that is rejected as being indefinite, above. Therefore claims 20-25, 27, 28, 45, 47 and 49 are also rejected as being indefinite.
New Claim Rejections - 35 USC § 103
22. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
23. Claims 1, 3-5, 8, 15-17, 19, 44-48, and 50-52 are 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).
Claim 1, as amended, is drawn to an encapsulated composition formulated for oral administration, comprising:
(i) an active agent comprising ketamine and/or pharmaceutically acceptable salts, enantiomers, derivatives or metabolites thereof (more specifically, 20% (S)-ketamine HCl, (embraced by claims 3-4 and 50));
(ii) one or more carrier compound(s) (more specifically, a co-polymer, and/or or a poloxamer, and/or a polysorbate, and/or Gelucire 48/16 (embraced by claims 5, 8, 51, and 52));
(iii) a viscosity modifier, 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;
(iv) 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 active agent (46).
Claim 15 is drawn to claim 1, and limits the viscosity modifier to a gum material (more specifically, Kelcogel CGHA at varying concentrations from 20%-50% (claims 16 and 17)).
Claim 19 is drawn to claim 1, comprising ketamine HCl, and one or more excipients, carriers or diluents selected from the group consisting of:
(i) PEG 1500;
(ii) PEG 6000;
(iii) Gelucire 44/14;
(iv) Polysorbate 80;
(v) Gelucire 48/16;
(vi) the viscosity modifier Kelcogel CGHA; and
(vii) the antioxidant BHT, and
wherein the composition is resistant to misuse and/or abuse (claim 45), and wherein the composition exhibits an immediate release of the active agent (claim 47).
In view of a broadest reasonable interpretation of claim 19, the recitation of “[t]he composition of claim 1, comprising ketamine hydrochloride and one or more excipients, carriers or diluents,” is construed to mean, “the composition of claim 1 comprising ketamine hydrochloride, and wherein the excipients, carriers, and/or diluents are selected from the group consisting of:”.
24. Mittur et al. disclose an oral abuse-deterrent composition in the form of a capsule comprising S-ketamine, 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
(iii) the viscosity modifier CARBOPOL® 974P,
(see Example 8, page 32).
25. 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. suggest the use of additional 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), but 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.
26. Yet, Daniely et al. teach an immediate release formulation for oral delivery in the form of a capsule, i.e., “ADAIR,” an immediate release (IR) abuse deterrent formulation (ADF), comprising 10 mg of active agent (dextroamphetamine), Poloxamer 124, Gelucire 48/16, and the viscosity modifier Kelcogel CGHA (gellan gum). Daniely et al. teach that the ADAIR capsule demonstrates superior abuse deterrent properties as compared to a comparator immediate release tablet (column 60, lines 10-44). 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 (iii) of claim 1 (page 287, left column, last sentence- right column, first sentence).
27. Thus one of skill in the art would have been motivated to modify the abuse deterrent composition of Example 8 of Mittur et al. by substituting Carbopol® 974P for the gellan gum viscosity modifier Kelcogel CGHA™ (aka gellan gum, comprising a tetrasaccharide repeating unit of one α-L-rhamnose, one β-D-glucuronic acid and two β-D-glucose residues), with a reasonable expectation of success. And, as noted by the court in In re Font, 675 F.2d 297 (CCPA 1982), an express suggestion to substitute one equivalent component (i.e., an equivalent gelling viscosity modifier) for another is not necessary to render such substitution obvious. In the instant case, (1) the prior art element of Example 8 performs the function specified in the claim with only insubstantial differences; (2) the claimed component (i.e., a gum viscosity modifier) and its function was known in the art; (3) a person of ordinary skill in the art would have recognized the interchangeability of the elements and could have substituted one known element for another; and (4) the results of the substitution would have been predictable, i.e., a gel material that swells when placed in an aqueous environment, thereby forming a viscous substance that significantly reduces and/or inhibits the ability of the active drug to be extracted from the dosage form.
28. Mittur et al. teach that “the material that gels” (i.e., corresponding to Applicant’s 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 claims 16 and 17.
As such, claims 1, 3-5, 8, 15-17, 19, 44-47 and 50 are prima facie obvious.
Claim 11 is drawn to claim 1, and limits the one or more carrier compound(s) to 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). Claim 13 is drawn to claim 1 and limits the one or more carrier compounds to Gelucire 48/16 at between 10% and 70% (v/v%), (more specifically, 50.55% (v/v%) Gelucire 48/16 (claim 14)).
29. 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 overlaps the range of carrier compound(s) of from 1%-70%, as required by instant claims 11-14. Regarding the weight % of components (ii) and (iii) in claims 11-14, 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.
30. 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 11-14 are prima facie obvious.
Claim 48 is drawn to the composition of claim 1 and limits wherein the dissolution of the active agent from the composition equates to an 80% recovery of the active agent after 30-45 minutes. Claim 49 is drawn to the composition of claim 19 and limits wherein the dissolution of the active agent from the composition equates to an 80% recovery of the active agent after 30-45 minutes.
31. Claims 48 and 49 are drafted in terms of an intended outcome which is an inherent property of the composition of claims 1, respectively: “…wherein dissolution of the active agent from the composition equates to an 80% recovery of the active agent after 30-45 minutes.” However, claims 48 and 49 are 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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32. 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, claims 48 and 49 are prima facie obvious.
33. Claims 6, 7, 9, 10, 18, 20-25, 27, 28, and 53 are 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), as applied to claims 1, 3-5, 8, 15-17, 19, 44-48, and 50-52, and further in view of Strickley, Robert, Pharmaceutical Research (2004).
Claims 1 and 5 are addressed in detail, above.
Claims 6 and 7 are drawn to claim 1, and limit the one or more carriers to PEG at varying concentrations from 1%-50% (v/v %).
Claim 9 is drawn to claim 1, and limits the one or more carrier compound(s) to Gellucire 44/14 at between 5% and 70% (v/v%) (more specifically, 20.68% (v/v%), 50.55% (v/v%), 55.14% (v/v%) or 59.74% (v/v%) (claim 10).
Claim 18 is drawn to claim 1 and limits the antioxidant to BHT.
Claim 20 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, Gelucire 44/14, and BHT. Claim 21 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, PEG 6000, Gelucire 44/14, Polysorbate 80 and BHT. Claim 22 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, PEG 6000, Gelucire 44/14, and BHT. Claim 23 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, PEG 1500, Gelucire 48/16, and BHT. Claim 25 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, PEG 1500, Polysorbate 80, Gelucire 44/14, and BHT. Claim 27 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, Gelucire 44/14, Polysorbate 80, and BHT. Claim 28 is drawn to claim 19, comprising the combinations of ketamine HCl, Kelcogel CGHA, PEG1500, Gelucire 44/14, and BHT
Claim 53 is drawn to claim 5, and limits wherein the PEGs are selected from the group consisting of (i) PEG 1000, (ii) PEG 1500, (iii) PEG 2000, (iv) PEG 6000, and (v) PEG 8000.
34. Mittur et al. in view of Daniely et al. suggest 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
(iii) the viscosity modifier Kelcogel CHGA, but do not teach the specific excipients, carriers or diluents recited.
35. However, Mittur et al. additionally disclose 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)). The immediate release abuse deterrent composition of Daniely et al. comprises Poloxamer 124, Gelucire 48/16, and Kelcogel CGHA.
36. Strickely teaches the advantages of employing solubilizing excipients in oral pharmaceutical formulations, i.e., to enhance solubility and stability, and specifically name common solubilizing excipients Polysorbate 80 (Table III, page 210), Gelucire 44/14 (Table III, page 211), and the antioxidant butylated hydroxy toluene (BHT) (Table 1, paged 205 and 206). Strickley teaches a subgenus of commonly employed solubilized oral formulations including polysorbate 80, Labrafil M2125CS, Gellucire 44/14, and SPAN 80 (page 209, left column under “Surfactants (Micelles) in Oral Formulations”).
37. Thus, one skilled in the art would have been motivated to choose Polysorbate 80, Gelucire 44/14, Poloxamer 124, Gelucire 48/16 and/or PEGs from the small genus of commonly employed carriers/ diluents/ excipients specifically named by Mittur et al., Daniely et al. and Strickley, to substitute for Labrafil M2125CS and SPAN 80 in the composition comprising S-ketamine of Example 8 of Mittur et al. One of skill in the art would also have been motivated to select the antioxidant BHT to employ in an oral capsule composition comprising S-ketamine HCl to enhance solubility and stability of said composition.
38. 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 overlaps the range of carrier compound(s) of from 1%-70%, as required by instant claims 6, 7, 9 and 10. Regarding the weight % of components (ii) and (iii) in claims 6, 7, 9 and 10, 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.
39. 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.
40. Regarding the additional components present in the composition taught by Mittur et al., Applicant employs the transitional term “comprising” in claim 1, which is synonymous with “including,” “containing,” or “characterized by,” i.e., is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) (“like the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended.”). Invitrogen Corp. v. Biocrest Manufacturing, L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003) (“The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps.”); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) (“Comprising” is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.); Moleculon Research Corp.v.CBS, Inc., 793 F.2d 1261, 229 USPQ 805 (Fed. Cir. 1986); In re Baxter, 656 F.2d 679, 686, 210 USPQ 795, 803 (CCPA 1981); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) (“comprising” leaves “the claim open for the inclusion of unspecified ingredients even in major amounts”). In Gillette Co. v. Energizer Holdings Inc., 405 F.3d 1367, 1371-73, 74 USPQ2d 1586, 1589-91 (Fed. Cir. 2005), the court held that a claim to “a safety razor blade unit comprising a guard, a cap, and a group of first, second, and third blades” encompasses razors with more than three blades because the transitional phrase “comprising” in the preamble and the phrase “group of” are presumptively open-ended. “The word ‘comprising’ transitioning from the preamble to the body signals that the entire claim is presumptively open-ended.” Id. In contrast, the court noted the phrase “group consisting of” is a closed term, which is often used in claim drafting to signal a “Markush group” that is by its nature closed. Id. The court also emphasized that reference to “first,” “second,” and “third” blades in the claim was not used to show a serial or numerical limitation but instead was used to distinguish or identify the various members of the group. Id. See MPEP 2111.03.
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As such, claims 6, 7, 9, 10, 18, 20-25, 27, 28 and 53 are prima facie obvious.
Response to Arguments
41. Applicant traverses the obviousness rejection, 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. "[W]hen the prior art teaches away from combining certain known elements, discovery of a successful means of combining them is more likely to be nonobvious." KSR International Co. v. Teleflex Inc., et al., 550 U.S. 398, 416 (2007) (emphasis added). Mittur at page 23, lines 9 to 15, describes how using a composition comprising the selected gelling polymer (i.e., Carbopol@) is desirable for buccal or sublingual administration to allow release and absorption through the mucosa of the buccal or sublingual cavity, e.g., prior to a patient swallowing the composition. Specifically, it is written that the mucoadhesive character of the polymer "allows the composition to adhere to the mucosa of the buccal or sublingual cavity of the patient and reduce the patient's tendency to swallow the composition before the [ketamine] has been released and absorbed through the mucosa of the buccal or sublingual cavity." Applicant argues that Mittur shows that the bioavailability of the sublingual formulation (Example 7) is higher than the two oral formulations (Examples 8 and 9, respectively). That is to say, the formulations show more substantial (and rapid) absorption when administered sublingually, compared to when the formulation is administered orally.
Applicant alleges that Mittur teaches away from oral compositions and towards buccal or sublingual administration of ketamine, which favor immediate release and improved absorption. Applicant argues that Mittur directs the skilled person away from oral administration and exemplifies oral compositions having lower rates and extents of release (higher tmax values and lower bioavailability) than when the formulations are administered sublingually.
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 (an example of a gellan gum comprising a repeating unit of the tetrasaccharide as defined in claim 1) in the example formulations not only limited the amount of ketamine recovered in the syringe-ability studies, but also provided a rapid release of ketamine in the gastric dissolution studies. Applicant references Examples 1 to 3, pages 21 to 31 of the instant application, and argue that this is not taught or suggested by Mittur.
42. Applicant's arguments have been fully considered but they are not persuasive. Regarding Applicant’s argument that Strickley 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 et al.’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.
(ii) Regarding the Strickley reference (which teaches common solubilizing excipients such as polysorbate 80 and Gelucire 44/14, named by Strickley. See Office Action, page 17), Applicant respectfully disagrees. Applicant argues that Strickley describes myriad formulations, each with a different specific combination of excipients, and makes no particular recommendation or teaching towards any particular excipients.
Applicant argues that the present application is directed to a novel cohort of compositions comprising excipients specifically selected for their combined abuse-deterrent and immediate release properties (see, for example, page 4, lines 27 to 32, of the application as filed). Applicant notes that Strickley is silent with respect to abuse-deterrent formulations, and makes only a passing mention of immediate release formulations (and in respect only of an intravenous formulation, and not in regard to oral formulations). In contrast, the present inventors have identified excipients that balance these (typically antagonistic) properties in the formulations disclosed.
43. Applicant's arguments have been fully considered but they are not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Mittur is relied upon for disclosing an abuse-deterrent ketamine formulation in the form of a capsule for oral administration, comprising the same active component (i) and carrier component (ii) as instantly claimed, differing only in component (iii). Daniely et al. teach an immediate release (IR) abuse-deterrent formulation (ADF) for oral delivery in the form of a capsule, comprising 10 mg of active agent, (ii) carrier component and (iii) viscosity modifier Kelcogel CGHA (gellan gum). Strickley is relied upon for teaching commonly employed pharmaceutical excipients in oral formulations.
44. Taken together, the combined prior art of record suggest an oral immediate release, abuse-deterrent composition in the form of a capsule comprising S-ketamine, wherein the ingredients facilitate an improved immediate release of the active agent, relative to other immediate release compositions,
Conclusion
45. Claims 1, 3-25, 27, 28, 32, 33, 44-48, and 50-53 are present in the application. Claims 32 and 33 are presently withdrawn from consideration. Claims 1, 3-25, 27, 28, 44-48, and 50-53 are rejected. No claim is presently allowed.
46. 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.
Correspondence
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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