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 .
Priority
Examiner acknowledges that, according to the Filing receipt received 05/08/2025, that the instant application 19/053,009 filed 02/13/2025 claims domestic benefit of U.S. provisional application 63/553,739 filed 02/15/2024. All of the instant claims have been awarded the effective filing date of 02/15/2024.
Information Disclosure Statement
The Information Disclosure Statement filed on 06/10/2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
Specification
The disclosure is objected to because of the following informalities: on page 20, all instances of "betonite" (at least lines 9 and 14) should read "bentonite".
Appropriate correction is required.
Claim Objections
Claim 17 is objected to because of the following informalities: "proteosome" should read "proteasome". Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 5, and 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Luo et al. (Journal of Medicinal Chemistry; 2022) as evidenced by Capdevila et al. (Neuroendocrinology; 2022).
Luo et al. discloses a method of treating streptozotocin-induced diabetic peripheral neuropathic pain in rats, comprising orally administering the below compound 34 (LX9211) following administration of streptozotocin (p. 4463, col. 2).
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Luo et al. discloses that administration of compound 34 significantly reduced mechanical allodynia without significant motor impairment (p. 4463, col. 2; p. 4464, col. 1). Compound 34 (LX9211) is identical to the compound set forth in instant claim 2.
As evidenced by Capdevila et al., streptozotocin is a chemotherapeutic agent used for the treatment of pancreatic neuroendocrine tumors (Abstract; p. 1157, col. 2). The method of Luo et al. therefore inherently discloses a method of treating chemotherapy-induced peripheral neuropathy.
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.
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.
Claim(s) 3-4, 6-7, 9, and 15-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Luo et al. (Journal of Medicinal Chemistry; 2022) as evidenced by Capdevila et al. (Neuroendocrinology; 2022) as applied to claims 1-2, 5, and 8 above, and further in view of Yang et al. (Journal of Experimental & Clinical Cancer Research; 2021; IDS filed 06/10/2025) and Kostich et al. (The Journal of Pharmacology and Experimental Therapeutics; 2016).
Luo et al., as evidenced by Capdevila et al., teaches as above. Luo et al. further discloses that AAK1 is widely expressed in the dorsal root ganglia (p. 4458, col. 2). Luo et al. additionally teaches that compound 34 showed inhibitory activity at Na and Ca channels (Table 6; p. 4462-4463 bridging paragraph).
Luo et al. does not teach a method of treating, managing, or preventing chronic or acute chemotherapy-induced peripheral neuropathy (CIPN), or that the AAK1 inhibitor and chemotherapeutic agent are administered concurrently, that the AAK1 inhibitor is administered before the chemotherapeutic agent, that the chemotherapeutic agent and AAK1 inhibitor are administered by the same route of administration, that the patient is undergoing chemotherapy for the treatment of colorectal cancer, or that the chemotherapeutic agent is chelated platinum. These limitations are obvious in view of Yang et al. and Kostich et al.
Yang et al. teaches that CIPN is a condition caused by cytotoxic drugs such as platinum, taxanes, proteasome inhibitors, vinca alkaloids, and immunomodulatory drugs that cause impairments to the peripheral and central nerve symptoms (p. 1, col. 1). Yang et al. teaches that oxaliplatin is a prominent neurotoxic chemotherapy agent, wherein the most common dose-limiting side effect is peripheral neuropathy (p. 1, col. 2 – p. 2, col. 2) which can be divided into acute and chronic forms (p. 3, col. 1). Yang et al. additionally teaches that the side effects of oxaliplatin contribute to reduction in treatment compliance of colorectal cancer patients (p. 1-2, bridging paragraph). Yang et al. teaches that an important mechanism of acute oxaliplatin-induced peripheral neuropathy (OIPN) is impairment of Nav channel activation in sensory neurons and nerve hyperexcitability, wherein the degree of acute neuropathy seems to predict development of chronic neuropathy (p. 3, cols. 1-2; p. 5, col. 2). Yang et al. further discloses that drug candidates for treatment of OIPN include combinations of Nav and Cav channel inhibitors, which have indicated synergistic effects (p. 17, col. 2). Yang et al. additionally teaches that the SNRI duloxetine is currently the only therapy recommended for treatment of CIPN (Table 6; p. 10, col. 2). Yang et al. also teaches that different modes of administration impact the analgesic effect and tolerability of certain medicaments when administered to treat OIPN (p. 13, Table 7, col. 3) and discusses the importance of optimizing a treatment schedule (p. 15, col. 1).
Kostich et al. teaches that AAK1 inhibition is linked to α2 adrenergic pathways, wherein administration of an α2 adrenergic receptor inhibitor blocked the antinociceptive effects of an AAK1 inhibitor in both thermal hyperalgesia and mechanical allodynia models (p. 382, col. 2 – p. 383, col. 2). Kostich et al. discloses that AAK1 inhibition is linked to major inhibitory pain pathways of the most commonly prescribed medications for neuropathic pain, including SNRIs, which act at least in part through α2 adrenergic pathways (p. 383, col. 2 – p. 384, col. 1 bridging paragraph).
It would be prima facie obvious for one of ordinary skill in the art to administer compound 34 (LX9211) for the treatment of oxaliplatin-induced peripheral neuropathy in a patient undergoing treatment for colorectal cancer. One would have been motivated to do so, with reasonable expectation of success, as LX9211 is effective in treating peripheral neuropathy. Moreover, LX9211 exhibits activity that has been shown to be beneficial for the treatment of oxaliplatin-induced peripheral neuropathy, both in its ability to inhibit Na and Ca ion channels and its inhibition of AAK1, which is linked to α2 adrenergic pathways shared by SNRIs currently used to treat OIPN such as duloxetine. As such, one would be apprised that the effects of LX9211 would be applicable to OIPN and further in patients commonly treated with oxaliplatin that are likely to suffer from OIPN, such as those with colorectal cancer.
Moreover, absent evidence of criticality or unexpected results, it would be prima facie obvious for one of ordinary skill in the art to adjust the dosing schedule and route of administration of LX9211 and the chemotherapeutic agent. One would have been motivated to do so, with reasonable expectation of success, in order to optimize the treatment of chemotherapy-induced peripheral neuropathy. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results). Moreover, as suggested by Yang et al., optimization of scheduling and mode of administration is important in order to determine methods by which patients will best respond to treatment.
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.
Claims 1-9 and 15-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 8-11 of U.S. Patent No. 12344596 in view of Luo et al. (Journal of Medicinal Chemistry; 2022) as evidenced by Capdevila et al. (Neuroendocrinology; 2022), Yang et al. (Journal of Experimental & Clinical Cancer Research; 2021; IDS filed 06/10/2025), and Kostich et al. (The Journal of Pharmacology and Experimental Therapeutics; 2016).
The claims of the ‘596 patent are directed toward a method of treating or managing neuropathic pain in a subject, comprising administering to a patient a therapeutically effective amount of a crystalline form of the compound shown below or a composition thereof.
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While the claims do not recite that the neuropathic pain is chemotherapy-induced peripheral neuropathy, chronic or acute chemotherapy-induced peripheral neuropathy (CIPN), or that the AAK1 inhibitor and chemotherapeutic agent are administered concurrently, that the AAK1 inhibitor is administered before the chemotherapeutic agent, that the chemotherapeutic agent and AAK1 inhibitor are administered by the same route of administration, that the patient is undergoing chemotherapy for the treatment of colorectal cancer, or that the chemotherapeutic agent is chelated platinum, these limitations are obvious in view of Luo et al. (as evidenced by Capdevila et al.), Yang et al., and Kostich et al.
Luo et al., as evidenced by Capdevila et al., teaches as in the above rejections under 35 U.S.C. 102 and 103. Yang et al. and Kostich et al. teach as in the above rejection under 35 U.S.C. 103.
It would be prima facie obvious for one of ordinary skill in the art to administer compound K, which is identical to LX9211 as in Luo et al., for the treatment of oxaliplatin-induced peripheral neuropathy in a patient undergoing treatment for colorectal cancer. One would have been motivated to do so, with reasonable expectation of success, as Luo et al. shows LX9211 is effective in treating peripheral neuropathy. Moreover, LX9211 exhibits activity that has been shown to be beneficial for the treatment of oxaliplatin-induced peripheral neuropathy, both in its ability to inhibit Na and Ca ion channels and its inhibition of AAK1, which is linked to α2 adrenergic pathways shared by SNRIs currently used to treat OIPN such as duloxetine. As such, one would be apprised that the effects of LX9211 would be applicable to OIPN and further in patients commonly treated with oxaliplatin that are likely to suffer from OIPN, such as those with colorectal cancer.
Moreover, absent evidence of criticality or unexpected results, it would be prima facie obvious for one of ordinary skill in the art to adjust the dosing schedule and route of administration of Compound K and the chemotherapeutic agent. One would have been motivated to do so, with reasonable expectation of success, in order to optimize the treatment of chemotherapy-induced peripheral neuropathy. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results) MPEP 2144.04(IV)(C). Moreover, as suggested by Yang et al., optimization of scheduling and mode of administration is important in order to determine methods by which patients will best respond to treatment.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MADELINE E BRAUN/Examiner, Art Unit 1624 10/14/2026
