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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claim 1-19) in the reply filed on 5/22/25 is acknowledged.
Examiner acknowledges Applicants’ remarks that the previous office action inadvertently states that claim 8 is directed to “patient is being administered an analgesic” and claim 9 is directed to “patient is not being administered an analgesic”.
Applicants further elect claim 8, as a species, directed to “the patient is not being administered an analgesic”. The election is without traverse.
Upon further consideration, the requirement for Election of species has been withdrawn.
Claims 1-19 have been considered for examination. Claim 20 has been withdrawn as being non-elected.
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.
Claim(s) 1, 7, 8 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ghoreishi-Haack et al (The Journal of Pharmacology and Experimental Therapeutics, September 2018, 366:485-497), as evidenced by Pain & Spine Specialists 2025.
Instant claim 1 is directed to a method of treating advanced painful diabetic peripheral neuropathy in a patient in need thereof, comprising administering daily to the patient a therapeutically effective amount of (2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide 5 (NYX-2925”), or a pharmaceutically acceptable salt thereof.
Ghoreishi-Haack teaches the claimed NYX-2925 as a novel NMDS receptor modulator that induces rapid and long-lasting analgesia. Ghoreishi-Haack teaches oral, intrathecal and Intravenous administration (abstract). Ghoreishi-Haack teaches oral administration at daily dosing and the effect measured at 1 hr, 24 hrs, 1 week and after 2 weeks of daily dosing (p 488, col. 1). For the claimed doses of NYX-2925 (claims 3-6), Ghoreishi-Haack teaches oral composition comprising NYX-2925 in a range or 0.1-100 mg/kg (page 486, col. 1), and particularly 10 mg/kg (col. 2, p 486).
Instant claim recited “advanced DPN”. Ghoreishi-Haack does not explicitly teach advanced DPN.
However, Pain & Spine Specialists reference teaches different stages of Diabetic Neuropathy, and describes pre diabetic, early stage diabetic, advanced diabetic stage diabetic neuropathy and late-stage diabetic neuropathy. Further the reference teaches that in the advanced stage DPN individuals may experience sensory ataxia, which can lead to impaired coordination and balance, posing challenges in daily activities. Furthermore, large fiber neuropathy resulting in slowing of nerve conduction can significantly affect the quality of life and activities of individuals dealing with this condition. The potential complications of advanced diabetic neuropathy extend to increased susceptibility to foot pain, infections, and even the risk of lower limb amputation if not diligently managed.
Ghoreishi-Haack teaches the efficacy of NYX-2925 in treating chronic, debilitating conditions arising from neuropathic pain in paw withdrawal latency (PWT) and teaches long lasting efficacy. Since Ghoreishi-Haack teaches administration of the same composition for treating the same DPN, the ability to treat advanced DPN is inherent to the method of Ghoreishi-Haack.
With respect to the effect of claim 7, though Ghoreishi-Haack fails to teach the reduced sleep interference for a week. However, the claimed property is inherent to the method of Ghoreishi-Haack because claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
Ghoreishi-Haack does not teach the presence of an analgesic along with NYX-2925, and hence meets claim 8.
For claim 17, Ghoreishi-Haack teaches daily administration of NYX-2925 (Description of Fig.2- on page 489, col. 1 & p 488, col. 1- Results).
Thus, Ghoreishi-Haack anticipates instant claims.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1-8 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Ghoreishi-Haack et al., as evidenced by Pain & Spine Specialists 2025.
Ghoreishi-Haack teaches the claimed NYX-2925 as a novel NMDS receptor modulator that induces rapid and long-lasting analgesia. Ghoreishi-Haack teaches oral, intrathecal and Intravenous administration (abstract). Ghoreishi-Haack teaches oral administration at daily dosing and the effect measured at 1 hr, 24 hrs, 1 week and after 2 weeks of daily dosing (p 488, col. 1). For the claimed doses of NYX-2925 (claims 3-6 & 16), Ghoreishi-Haack teaches oral composition comprising NYX-2925 in a range or 0.1-100 mg/kg (page 486, col. 1), and particularly 10 mg/kg (col. 2, p 486), which overlaps with the claimed amounts “about 10 mg to about 200 mg”. However, the reference teaches that the treatment provides long lasting analgesic effects (p 489, col. 2) with increased effect at dose levels of 1, 10 and 30 mg/kg. Therefore, it would have been obvious for one of an ordinary skill before the effective filing date of the instant invention to employ optimum amounts of NYX-2925 to administer to advance DPN patients with an expectation to provide an effective treatment for advance DPN patients because Ghoreishi-Haack teaches overlapping amounts of NYX-2925. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). With respect to claims 2 and 7, Ghoreishi-Haack fails to explicitly teach that the subject has suffered from painful DPN for longer than 1 year, 2 years, 3, years or 4 years, and that the patient has reduced sleep interference after about 1 week, 2, 3, 4, 5 or more weeks. However, one of an ordinary skill in the art would have been able to administer the composition comprising NYX-2925 to subjects who are suffering from DPN for a longer time because Ghoreishi-Haack teaches that NYX-2925 provides a long-lasting effect. Even though Ghoreishi-Haack fails to teach that the DPN is characterized by a MNSI score of greater than or equal to 3 (claim 16), one of an ordinary skill in the art would have been able to treat DPN with a score of equal to greater than 3 because the reference teaches the same composition and for the treatment of the same condition i.e., DPN, that provides a long-lasting effect.
Claim(s) 1, 7, 8 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Ghoreishi-Haack et al., as evidenced by Pain & Spine Specialists 2025, as applied to claims 1, 7, 8 and 17, and further in view of Patel et al.
For claim 18, Ghoreishi-Haack does not teach the claimed monohydrate of NYX-2925.
However, choosing a base compound or a suitable salt form of NYX-2925 with an expectation to provide the same or improved effective treatment of DPN because Patel teaches that converting a drug into a salt through this process can increase its chemical stability, render the complex easier to administer and allow manipulation of the agent’s pharmacokinetic profile, and that salt selection is a common standard operation performed with small ionizable molecules during drug development, and in many cases the drug salts display preferential properties as compared with the parent molecule (abstract).
Claims 1, 7, 8, 9-15, 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ghoreishi-Haack et al., as evidenced by Pain & Spine Specialists 2025 as applied to claims 1, 7, 8 and 17 above, and further in view of US 8945620 to Brockbader et al (Brockbader).
Ghoreishi-Haack fails to teach the oral composition of claim 10-15, and the presence of analgesic of claim 9.
Brockbader teaches solid pharmaceutical composition comprising pregabalin for treating disorders such as diabetic peripheral neuropathy (claim 9 of the reference). Pregabalin reads on the instant analgesic compound. The solid composition includes excipients such as diluents, fillers, for providing enhanced physical properties of the tablets, and includes the claimed microcrystalline cellulose, pregelatinized starch (col. 11, l 30-45) and magnesium stearate as lubricants (col. 11, l 16-29). Brockbader further teaches that the solid composition in the form of tablets, capsules, sachets etc (col. 3, l 36-41 and example 32). Hence, it would have been obvious for one of an ordinary skill before the effective filing date of the instant invention to prepare the composition of Ghoreishi-Haack, comprising NYX-2925, and further modify the composition to include pregabalin because both Ghoreishi-Haack and Brockbader teach analogous art i.e., both references teach compounds for effectively treating diabetic peripheral neuropathy. Therefore, one of an ordinary skill in the art would have expected at least an additive effect with the compounds taught for the same treatment. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." For claim 19, while the claimed composition requires NYX-2925 with the claimed XRDP, it is not required that the composition requires the compound to remain in a crystalline state, and further the claim does not limit the composition to a particular solid or liquid form. Hence, one of an ordinary skill in the art would have been able to prepare the oral composition comprising NYX-2925 in the form of tablets comprising the claimed microcrystalline cellulose, pregelatinized starch (col. 11, l 30-45) and magnesium stearate as suitable excipients in enhancing the property of the tablets or capsules, because one of an ordinary skill in the art would have recognized suitable oral formulations for administering DPN treating compounds NYX-2925 and pregabalin, from the teachings of Brockbader,
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKSHMI SARADA CHANNAVAJJALA whose telephone number is (571)272-0591. The examiner can normally be reached Generally M- F 9 AM to 6 PM.
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/LAKSHMI S CHANNAVAJJALA/Primary Examiner, Art Unit 1611