DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Status of the Claims
The response filed 04/16/2026 is acknowledged.
Claims 14-32 are pending.
Applicant’s election without traverse of the species sodium vanadate (Na3VO4) in the reply filed on 10/22/2025 is acknowledged.
Applicant has indicated the claims 14-17, 19, 21-22, and 27-32 read on the elected species.
Claims 18, 20, and 23-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/22/2025.
Note: US 12383562 may be relevant for double patenting if withdrawn species are rejoined.
Claims 14-17, 19, 21-22, and 27-32 are treated on the merits in this action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Withdrawn
The rejection of claims 14-17, 19, 21-22, and 27-32 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subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention has been withdrawn because of Applicant’s amendment.
The rejection of claim 30 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subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention has been withdrawn because of Applicant’s amendment.
The rejection of claim 31 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 pre-AIA the applicant regards as the invention has been withdrawn because of Applicant’s amendment.
The rejection of claims 14-17, 19, 21-22, 27-29, and 32 under 35 U.S.C. 102(a)(1) as being anticipated by Li, Chinese Pharmacological Bulletin, 2011 (cited on Applicant’s IDS dated 10/22/2025) has been withdrawn because of Applicant’s amendment.
Response to Arguments
Applicant's arguments filed 04/16/2026 have been fully considered but they are not persuasive.
Applicant argues Li only discloses intrathecal administration of PTP inhibitor to study the effect of PTP on inflammatory pain. In the study of Li, sodium orthovanadate was used as a PTP inhibitor. Spinal protein tyrosine phosphatase is a receptor-type protein complex phosphatase, which has tissue-specific expression and mainly exists in the spinal cord, but usually there is no detectable level in blood circulation. Thus, the intrathecal administration in Li is critical.
This argument is unpersuasive. Applicant acknowledges that Li teaches sodium vanadate is a PTP inhibitor, but argues protein tyrosine phosphatase (PTP) is only present in the spinal cord. However, PTPs are not only present in the spinal cord. For example, Stanford, Arthritis Rheumatol, 2016 teaches protein tyrosine phosphatase is present in the synovial lining of the joints, and further its activation promotes arthritic disease progression. See Stanford, e.g., pp. 1-2, Abstract, Results and Conclusions. Since pain is a symptom of arthritis as evidenced by Cruz, PTP plays a critical role in promoting pain associated with arthritis. Since sodium vanadate was a known inhibitor of PTP as evidenced by Li, administering sodium vanadate topically (transdermal), intravenously, subcutaneously as suggested by Cruz would result in inhibiting PTP present in the synovial lining of arthritic joints, thereby inhibiting arthritis progression and pain resulting therefrom.
Applicant argues Li does not teach any other route of administration other than intrathecal administration. Applicant argues Li teaches PTP inhibitor sodium orthovanadate controls pain by inhibiting protein tyrosine phosphatase in the spinal cord. Applicant argues those skilled in the art would not have motivation to administer sodium orthovanadate using subcutaneous, intramuscular, intravenous or oral administration with a reasonable expectation of successfully reaching PTP in the spinal cord as needed to treat pain.
This argument is unpersuasive.
Cruz teaches administering sodium orthovanadate (Cruz, e.g., claims 5 and 8), to subjects suffering from arthropathy (Cruz, e.g., claim 1). Cruz teaches methods of administering vanadate compounds for treating cancer or arthritis, wherein the vanadate compounds are administered topically (transdermal), intravenously, subcutaneously (Cruz, e.g., c8:14-29). Cruz teaches arthropathy includes multiple inflammatory diseases such as arthritis. Cruz teaches arthropathy is considered to be reduced if at least one symptom of arthropathy is beneficially altered. Cruz teaches pain was a known symptom of arthropathic diseases. See Cruz, e.g., c13, ¶ 1. Cruz teaches the dose may by optimized to provide an effective concentration of the orthovanadate in body fluids including serum, synovial fluid, or cerebral spinal fluid (Cruz, e.g., c9:15-26).
It is clear then, that the skilled artisan would have understood that Cruz suggests topical, intravenous, or subcutaneous administration of vanadate compounds to subjects suffering from pain. The skilled artisan also understood that Cruz suggests that topical, intravenous, or subcutaneous were known routes of administration effective to provide vanadate compounds to cerebrospinal fluid, and more generally, routes of administration for sodium vanadate effective for treating subjects suffering from pain. Based on Li and Cruz, the skilled artisan would have had a reasonable expectation of successfully administering sodium vanadate using routes of administration including topical (transdermal), intravenous, or subcutaneous to achieve spinal fluid concentrations of vanadate, and that this the dose could be optimized to achieve effective amounts of vanadate compounds in the spinal fluid to ameliorate inflammatory pain associated with arthritis.
Further, arguendo, even if there was some doubt that topical (transdermal), intravenous, or subcutaneous routes of administration would be able to provide effective doses to the cerebral spinal fluid, the skilled artisan still had motivation to administer sodium vanadate topically (transdermal), intravenously, subcutaneously to subjects suffering from pain symptoms as reported in Cruz, to treat localized or somatic pain, e.g., as found in arthritis, and for sustained release and lowered toxicity risk.
Regression of arthritis as reported in Cruz, e.g., Example 16, would have led the skilled artisan to conclude that the symptoms of arthritis including pain are alleviated as well since Cruz notes that regression means symptoms of arthropathy, e.g., pain, are alleviated (Cruz, e.g., c13:1-15).
Applicant argues Cruz does not cure the deficiencies of Li. In particular, Applicant argues treating a mammal having an arthropathy, comprising administering to the mammal an amount of a vanadate or a vanadyl compound and an antioxidant effective to reduce or inhibit the arthropathy (Cruz, claim 1). Although Cruz discloses pain as a symptom of arthropathy, the symptoms of arthropathy include not only pain, but also redness, swelling, stiffness, decreased mobility, joint changes, etc.
This argument is unpersuasive. As acknowledged by Applicant, Cruz teaches administering sodium vanadate for treating symptoms of arthropathy, including pain. Thus, Cruz teaches topically (transdermal), intravenously, or subcutaneously administering sodium vanadate to subjects suffering from pain symptoms. Li also teaches sodium vanadate is effective to treat inflammatory pain. Therefore, Cruz is not the only reference of record which teaches treating subjects suffering from inflammatory pain. Cruz teaches arthropathy includes multiple inflammatory diseases such as arthritis, and Cruz teaches arthropathy is considered to be reduced if at least one symptom of arthropathy is beneficially altered. Cruz teaches pain was a known symptom of arthropathic diseases. See Cruz, e.g., c13, ¶ 1.
Applicant argues Cruz does no test of analgesic effects in arthritis. Thus, Applicant argues that although Cruz lists pain as one of the symptoms of arthritis, it is not a characteristic symptom of arthritis, and Cruz has not shown any analgesic effect of its treatment. Therefore, Applicant argues it cannot be reasonably considered that Cruz teaches or suggests that vanadium compounds can alleviate pain caused by arthropathy, much less pain in general.
This argument is unpersuasive. The claimed invention, incorporating the elected species, requires administering sodium orthovanadate to a subject suffering from pain. Li teaches administering sodium orthovanadate to subjects for treating inflammatory pain. Cruz teaches administering sodium orthovanadate to subjects suffering from pain, i.e., because pain is a symptom of inflammatory arthropathic conditions, e.g., arthritis.
In response to Applicant’s argument that pain is not a characteristic symptom of arthritis, it is noted that the Villa-Forte, Merck Manual, 2019, clearly indicates pain is characteristic to subjects having arthritis, e.g., arthritis is characterized by the combination of joint inflammation and pain (Villa-Forte, e.g., pg. 1: joints may simply be painful (arthralgia) or also inflamed (arthritis)). Cruz, example 17, reports subcutaneous administration of a vanadate compound (Cruz, e.g., ¶ spanning c21-c22) resulted in significant regression of established collagen induced arthritis (CIA) compared to control (Cruz, e.g., c24:36-55). The skilled artisan can only conclude that regression of arthritis means the symptoms of arthritis are reduced including the pain associated with arthritis even if Cruz did not test for analgesic effect.
Applicant’s argument that the skilled artisan would not have combined Li and Cruz because they concern different targets located in different tissues is unpersuasive. The skilled artisan would have considered the teachings of both references in combination at least because Li and Cruz both teach methods which comprise administering sodium orthovanadate to treat subjects suffering from pain.
Further in this regard, Stanford notes protein tyrosine phosphatases are present in joints and contribute to arthritis disease progression with pro-inflammatory signaling. Knockout of PTP protected mice from arthritis development (Stanford, e.g., Abstract, Results). As evident from Stanford, both Li and Cruz teach treating subjects having pain using sodium orthovanadate, and wherein at each target tissue site pain symptoms are mediated by the same target, i.e., protein tyrosine phosphatase.
Applicant has argued advantageous effects shown in the application could not have been reasonably expected based on Li and Cruz. Applicant argues the application shows analgesic effect of injections containing tetravalent vanadium compounds or pentavalent vanadium compounds. See examples 1-20. The remarks present data for oral administration.
The data has been considered but is unpersuasive.
The data in the specification is shown for a single route of administration at particular doses of specific vanadium compounds. The scope of claim 14 reads on any positive-tetravalent vanadium compound or a positive-pentavalent vanadium compound comprising a vanadium-oxygen bond. The scope of claim 14 reads on any dose. The scope of claim 14 excludes the route of administration by which the proffered data was obtained (intraperitoneal). Therefore, the data proffered refers only to the specific examples in the application rather than the individual claims of the application. As such the objective evidence of nonobviousness is not commensurate in scope with the claims. See MPEP § 716.
Applicant has not explained which doses of the specific vanadium compounds show unexpected results, therefore the amounts of claim 31 do not appear to be commensurate in scope with the claimed invention.
For the case of the elected species, Applicant has not explained which combination of route of administration and dose of sodium orthovanadate show unexpected results. Applicant has the burden of explaining proffered data. See MPEP 716.02(b). Thus, the scope of the presently claimed invention cannot be meaningfully compared with the proffered data.
The data for oral administration is not found in the specification. Arguments by Applicant cannot take the place of evidence. See MPEP 716.01(c), II.
Claim Rejections - 35 USC § 103
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 of this title, 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.
Claims 14-17, 19, 21-22, 27-29, 30-31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Chinese Pharmacological Bulletin, 2011 (cited on Applicant’s IDS dated 10/22/2025) and Cruz, US 5871779.
Li teaches administering sodium orthovanadate to a subject suffering from pain by injection (intrathecal) and reports a significant analgesic effect (Li, entire document, e.g., Abstract and conclusion). Li teaches sodium orthovanadate was a known protein tyrosine phosphatase inhibitor (Li, entire document, e.g., Abstract).
Li teaches administration by injection but does not expressly teach administering subcutaneously, intramuscularly, intravenously, or orally.
Cruz teaches methods of administering vanadate compounds for treating cancer or arthritis, wherein the vanadate compounds are administered topically (transdermal), intravenously, subcutaneously (Cruz, e.g., c8:14-29). The skilled artisan may select these administration options for slow, continuous release (Cruz, e.g., c8:14-29). Slow administration reduces toxicity of vanadate administration (Cruz, e.g. Example 9). Cruz provided the skilled artisan a suggestion to administer vanadate compounds, like sodium orthovanadate, to subject by transdermal, intravenous or subcutaneous administration to reduce toxicity and to treat localized sources of pain, e.g., arthritis.
Cruz teaches arthropathy is considered to be reduced if at least one symptom of arthropathy is beneficially altered. Cruz teaches pain was a known symptom of arthropathic diseases. See Cruz, e.g., c13, ¶ 1. Cruz teaches the dose may by optimized to provide an effective concentration of the orthovanadate in body fluids including serum, synovial fluid, or cerebral spinal fluid (Cruz, e.g., c9:15-26).
It is clear then, that the skilled artisan would have understood that Cruz suggests topical, intravenous, or subcutaneous administration of vanadate compounds to subjects suffering from pain. The skilled artisan also understood that Cruz suggests that topical, intravenous, or subcutaneous were known routes of administration effective to provide vanadate compounds to cerebrospinal fluid, and more generally, routes of administration for sodium orthovanadate effective for treating subjects suffering from pain. Based on Li and Cruz, the skilled artisan would have had a reasonable expectation of successfully administering sodium orthovanadate using routes of administration including topical (transdermal), intravenous, or subcutaneous to achieve spinal fluid concentrations of orhtovanadate, and that this the dose could be optimized to achieve effective amounts of vanadate compounds in the spinal fluid to ameliorate inflammatory pain associated with arthritis.
Further, arguendo, even if there was some doubt that the routes of topical (transdermal), intravenous, subcutaneous routes of administration would be able to provide effective doses to the cerebral spinal fluid, the skilled artisan still had motivation to administer sodium vanadate topically (transdermal), intravenously, or subcutaneously to subjects suffering from tissue specific pain symptoms as reported in Cruz, such as subjects suffering from arthritis for sustained release and lowered toxicity risk.
Regression of arthritis as reported in Cruz, e.g., Example 16, would have led the skilled artisan to conclude that the symptoms of arthritis including pain are alleviated as well since Cruz notes that regression means symptoms of arthropathy, e.g., pain, are alleviated (Cruz, e.g., c13:1-15).
It would have been obvious before the effective filing date of the presently claimed invention to combine the teachings of Li and Cruz with a reasonable expectation of success. It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a method for treating pain, e.g., as understood from Li, by administering sodium orthovanadate, e.g., topically (transdermal), intravenously, or subcutaneously according to the teachings of Cruz with a reasonable expectation of success. The skilled artisan would have been motivated to modify Li’s method by administering sodium orthovanadate intravenously or subcutaneously to enable sustained treatment with lower toxicity. The skilled artisan would have had a reasonable expectation of success because Cruz also teaches therapeutic methods of administering orthovanadates in the context of diseases characterized by pain.
Applicable to claim 31: Li does not expressly teach the dose recited in claim 31.
However, Cruz teaches doses within the range recited in claim 31 were known and used to administer vanadate compounds for a variety of conditions. For example, for treating tumors, arteriosclerosis, and mental syndromes, doses ranging from 0.0043 mg/kg to 0.14 mg/kg were suggested (Cruz, e.g., c2:22-30). Further, Cruz teaches effective doses generally ranging from 0.2 mg/kg to 25 mg/kg (Cruz, entire document, e.g., c8:43-63) for a variety of administration routes. Cruz suggests the doses are effective to reduce symptoms in subjects having arthropathy, e.g., arthritis, wherein the symptom is pain (Cruz, e.g., c13:1-15).
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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious before the effective filing date of the presently claimed invention to optimize Li’s method starting from known safe and effective dosing ranges suggested by the prior art for other vanadate treatments with a reasonable expectation of success. Since vanadate has a known dose dependent toxicity, the skilled artisan would have looked to the prior art, such as Cruz, to determine safe dosing ranges within which to optimize the dose of sodium vanadate for treating pain with a reasonable expectation of success. The skilled artisan would have had a reasonable expectation of success because Cruz suggests doses which may be effective to reduce symptoms such as pain.
Accordingly, the subject matter of claims 14-17, 19, 21-22, 27-29, 30-31 and 32 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
/SUSAN T TRAN/Primary Examiner, Art Unit 1615
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