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 .
This is a Final Office Action.
Election/Restrictions
Applicant's election without traverse (July 21, 2025) of the following species (August 30, 2025):
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The elections are acknowledged. Applicant has not pointed to any errors in the Examiner’s analysis of the different inventions. The requirement is deemed proper and is therefore made FINAL.
Based on species #1, 2, 3 and 4, claims 1-4, 8, 9 and 12-14 read on the elected invention.
Claims 1, 9, 12-14, 37-39, 46 and 56-62 are pending and claims 1, 9 and 60-62 are under examination. Claims 59-62 are new claims. Claims 12-14, 37-39, 46 and 56-59 are withdrawn based on the species election.
Claim 1 has been amended to embrace paclitaxel. Therefore, claims 12-14 are withdrawn based on the species election.
Newly submitted claim 59 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: claim 59 further comprises administering to the subject radiation therapy, thermotherapy or both, which was not previously presented for the species election.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 59 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Rejections - 35 USC § 112
Claim 4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the word “derivative” is withdrawn based on the amendments.
Claim 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the term “patches/cream” is withdrawn based on the amendments.
The rejection of claim 4 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for pharmaceutically acceptable salts, does not reasonably provide enablement for prodrugs, is withdrawn based on the amendments.
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.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 1-4, 8 and 9 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Tanabe et al. (WO 2007081060) as evidenced by Fong et al. (Plastic Reconstructive Surgery, 2014, 134(4 Suppl 2), 8S-14S), is withdrawn based on the amendments.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 9 and 60-62 under AIA 35 U.S.C. 103(a) as being unpatentable over Tanabe et al. (WO 2007081060) in view of Fong et al. (Plastic Reconstructive Surgery, 2014, 134(4 Suppl 2), 8S-14S), is withdrawn based on the amendments.
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1, 9 and 60-62 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Tanabe et al. (WO 2007081060) in view of Fong et al. (Plastic Reconstructive Surgery, 2014, 134(4 Suppl 2), 8S-14S), Huang et al. (Molecular Medicine Reports, 2012, 6, 1013-1017), and Reeves et al. (Cancer, October 15, 2012, 5171-5178) and O’Flaherty et al. (PLOS One, April 10, 2019, 1-17).
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The present application claims a method of treating pathologic pain comprising administering to a subject having pathological pain associated with cancer kenpaullone:
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, or a pharmaceutically acceptable salt there of such that K+/Cl- cotransporter (KCC2) gene expression is enhanced in neurons in the subject and administering paclitaxel. The K+/Cl- cotransporter (KCC2) gene expression enhanced in neurons and claim 62, drawn to the enhanced KCC2 gene expression, are a characteristic of the treatment.
Tanabe et al. teach the elected species as a therapeutic agent for the treatment of neuropathic pain, see page 3, first paragraph, see also the WIPO translation, page 5-17, section (2), subsection (1).
Fong et al. teach neuropathic pain as a species of pathologic pain, see page 9S, Table 1.
Tanabe further teaches the treatment of cancer pain, see claim 4 on page 7 in the newly provided translation of the reference. The reference further teaches parental administration, see page 5 of the translated document, first full paragraph.
Huang et al. teaches that paclitaxel may be used to treat osteosarcoma, a bone cancer, see page 1014, Figure 1(A).
Reeves et al. teaches paclitaxel causes paclitaxel-associated acute pain syndrome, which is associated with development of peripheral neuropathy, see title and abstract.
Moreover, O’Flaherty et al. teaches the combination of a GSK inhibitor (CHIR99021) and paclitaxel for the treatment of NSCLC, see the abstract, although the GSK inhibitor is not the elected species of formula (IV) or bone cancer.
Thus, it would have been obvious at the time of filing to co-administer a pain medication with paclitaxel since Reese teaches paclitaxel causes paclitaxel-associated acute pain syndrome and Tanabe teaches kenapaullone can be used to treat pain associated with cancer.
Thus, said claims are rendered obvious.
Claims 1, 9 and 60-62 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Tanabe et al. (WO 2007081060) in view of Fong et al. (Plastic Reconstructive Surgery, 2014, 134(4 Suppl 2), 8S-14S), Huang et al. (Molecular Medicine Reports, 2012, 6, 1013-1017) and O’Flaherty et al. (PLOS One, April 10, 2019, 1-17).
The present application claims a method of treating pathologic pain comprising administering to a subject having pathological pain associated with cancer kenpaullone:
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, or a pharmaceutically acceptable salt there of such that K+/Cl- cotransporter (KCC2) gene expression is enhanced in neurons in the subject and administering paclitaxel. The K+/Cl- cotransporter (KCC2) gene expression enhanced in neurons and claim 62, drawn to the enhanced KCC2 gene expression, are a characteristic of the treatment.
Tanabe et al. teach the elected species as a therapeutic agent for the treatment of neuropathic pain, see page 3, first paragraph, see also the WIPO translation, page 5-17, section (2), subsection (1).
Fong et al. teach neuropathic pain as a species of pathologic pain, see page 9S, Table 1, wherein neuropathic pain is due to disease.
Huang et al. teaches the paclitaxel may be used to treat osteosarcoma, a bone cancer, see page 1014, Figure 1(A).
Moreover, O’Flaherty et al. teaches the combination of a GSK inhibitor (CHIR99021) and paclitaxel for the treatment of NSCLC, see the abstract, although the GSK inhibitor is not the elected species of formula (IV) or bone cancer.
However, it would be obvious to combine the elected species with paclitaxel to treat pain derived from bone cancer since the elected species is known to treat neuropathic pain and paclitaxel is known to treat bone cancer. Moreover, O’Flaherty teaches the combination of GSK inhibitor with paclitaxel.
Therefore, claims 1, 9 and 60-62 are rendered obvious.
Applicant traverses the above 103 rejections by stating, “The rejections based on these combinations of references fail to satisfy the 3 requirements of prima facie obviousness. These references fail to teach or disclose each of the limitations of currently pending independent Claim 1. In the absence of such teachings, these references fail to suggest to the skilled person how to combine and/or modify the references to arrive at the currently claimed subject matter. Consequently, the cited references cannot provide the skilled person with any reasonable expectation of successfully arriving at the claimed subject matter by combining and/or modifying these teachings.”
This is not persuasive.
Applicant further argues each reference separately as noted below.
Applicant notes, “Tanabe fails to teach or suggest (i) that kenpaullone enhances KCC expression, (ii) enhanced KCC expression in neurons, (iii) paclitaxel, administering paclitaxel, or administering paclitaxel in combination with kenpaullone, (iv) reducing intracellular chloride ion levels in those neurons with enhanced KCC expression, or (v) increasing chloride ion efflux in those neurons with enhanced KCC expression.”
Indeed, Tanabe does not teach the combination of kenpaullone and paclitaxel, which is the reason for the obviousness versus the anticipatory rejection. The combination of the references provides the motivation to combine kenpaullone and paclitaxel. Points (i), (ii), (iv) and (v) from Applicant’s remarks are characteristics of the administration of kenpaullone. If, arguendo, these characteristics are only seen at specific concentrations, optimizing the concentration is considered obvious as result-effective variable, unless there is evidence to the contrary. However, there is nothing the specification that states otherwise.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "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." In re Aller, 220 F.2d 454, 105 USPQ 233, 235 (CCPA 1955). The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the solvents taught by the cited references), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
Applicant further notes, “Fong, which the Office Action relied upon for teaching "neuropathic pain as a species of pathologic pain", fails to cure Tanabe's numerous deficiencies.”
The Fong reference was used as evidence to define neuropathic pain as a species of pathologic pain; nothing more.
Applicant addresses the next reference by stating, “Huang, which the Office Action relied upon for teaching that "paclitaxel may be used to treat osteosarcoma, a bone cancer", similarly fails to cure the deficiencies of the combination of Tanabe and Fong. For instance, Huang evaluated the "cytotoxic effects of a combination of paclitaxel and etoposide on an osteosarcoma cell line in the presence of hyperthermia". Huang does not teach or suggest, however, (i) kenpaullone, (ii) that kenpaullone enhances KCC expression, (iii) enhanced KCC expression in neurons, (iv) administering paclitaxel in combination with kenpaullone, (v) reducing intracellular chloride ion levels in those neurons with enhanced KCC expression, or (vi) increasing chloride ion efflux in those neurons with enhanced KCC expression.”
Applicant is correct that Huang does not teach the combination of kenpaullone and paclitaxel, which is the reason for the obviousness versus the anticipatory rejection. The combination of the references provides the motivation to combine kenpaullone and paclitaxel. Points (i), (ii), (iv) and (v) from Applicant’s remarks are characteristics of the administration of kenpaullone as noted above, which is equally applicable here.
Applicant addresses the next reference as follows, “Reeves, which the Office Action relied upon for teaching that "paclitaxel causes paclitaxel- associated acute pain syndrome, which is associated with development of peripheral neuropathy", cannot cure the deficiencies of the Tanabe, Fong, and Huang. While Reeves teaches that paclitaxel is associated with "paclitaxel-induced arthralgias and myalgias" and "paclitaxel-associated acute pain syndrome", Reeves also teaches that "[t]o date, no therapy has been proven to be beneficial for preventing P-APS or paclitaxel-associated peripheral neuropathy". Therefore, Reeves advises that "[u]ntil effective agents are available, patients should be advised of P-APS and instructed on appropriate use of over-the-counter analgesics and/or opioid pain medications to ameliorate short term toxicities." From this, the Office Action stated that it would have been obvious to administer a pain medicine with paclitaxel. (Office Action, p. 9). However, in view of risks of a subject developing P-APS or paclitaxel-associated peripheral neuropathy, Reeves serves to (i) dissuade the skilled person from using paclitaxel all together, and/or (ii) encourage the skilled person to employ a dosing strategy that can minimize the long term effects of P-APS or paclitaxel-associated peripheral neuropathy. Neither of these suggestions are sufficient to motivate the skilled person to add paclitaxel (an agent that synonymous with "paclitaxel-induced arthralgia and myalgias", "paclitaxel-associated acute pain syndrome", and peripheral neuropathy) to the claimed method of treating pain by administering kenpaullone. There is no suggestion in Reeves (or in the combination of any of the cited references) to treat pain with an agent that induces pain. Simply stated, the skilled person would not be motivated to use an agent known to cause significant and prolonged pain in the claimed method of treating pain.”
This is not persuasive. A skilled person would be motivated to co-administer a drug that would alleviate a side-effect of the primary drug during treatment. The Reeves reference was provided to teach paclitaxel causes paclitaxel- associated acute pain syndrome, which is associated with development of peripheral neuropathy. The fact that Reeves there is no therapy proven to be beneficial for preventing P-APS or paclitaxel-associated peripheral neuropathy does not teach away from the treatment of P-APS. Reeves further teaches to use an analgesic, e.g. over-the-counter analgesics and/or opioid pain medications to ameliorate short term toxicities. This is in support of administering an analgesic with paclitaxel.
Applicant addresses the last reference by contending, “O'Flaherty, which the Office Action relied upon for teaching the "combination of a GSK inhibitor (CHIR99021) and paclitaxel for the treatment of NSCLC". (Office Action, p. 10). This is not unexpected as paclitaxel is a well-known chemotherapeutic agent and O'Flaherty reports that increased GSK3 expression and/or activity has been observed in several cancers including non-small cell lung cancer (NSCLC). Nevertheless, O'Flaherty fails to teach or suggest (i) kenpaullone, (ii) that kenpaullone enhances KCC expression, (iii) enhanced KCC expression in neurons, (iv) administering paclitaxel in combination with kenpaullone, (v) reducing intracellular chloride ion levels in those neurons with enhanced KCC expression, (vi) increasing chloride ion efflux in those neurons with enhanced KCC expression, or (vii) treating pain with kenpaullone as currently claimed.”
This is unpersuasive for the reasons provided above which address points (i), (ii), (iv) and (v) as noted above, which is equally applicable here.
Moreover, one cannot attack references individually, when the rejection is premised on the combination of the references. In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). (Nonobviousness cannot be established by attacking the references individually where the rejection is based upon the teachings of a combination of references.)
Therefore, the rejection is maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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