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 .
DETAILED ACTION
Status of 17/912,918
Claims 15, 17-20, 22-30, 32-34, and 36 are currently pending.
Priority
Instant application 17/912,918, filed 9/20/2022, claims priority as follows:
PNG
media_image1.png
112
359
media_image1.png
Greyscale
The foreign applications were not submitted as certified, translated documents in English, and therefore priority cannot be granted for claims 15, 17-20, and 22-36. Thus, the effective filing date of claims 15, 17-20, and 22-36 is the PCT filing date, 3/19/2021.
Applicant has not submitted the translated foreign priority documents as of 10/8/2025 and has presented arguments against doing so. However, determining the effective filing date of the invention requires a claim-by-claim analysis, which the Examiner is unable to complete because the foreign applications are not translated to English. See MPEP § 2152.01. Thus, if Applicant would like to the Examiner to perform this claim-by-claim analysis and potentially grant the earlier effective filing date based on the contents of the documents, the Examiner is requiring certified translations of the foreign applications to English. Additionally, the Examiner is requiring certified translations of the foreign applications to English as per 37 C.F.R. 1.55(g)(3)(iii). The Examiner recognizes the references relied upon below are from 2013, before the submission of the foreign documents; however, the fact remains that if Applicant would like the Examiner to go on record and grant the earlier effective filing date, the Examiner is requiring a certified English translation and for the foreign priority documents to contain support for the instant claims.
Information Disclosure Statement
All references from the IDS’s submitted on 12/02/2022, 10/10/2023, and 4/11/2024 have been considered unless marked with a strikethrough.
Response to Applicants Arguments/Amendments
The amendment entered 8/18/2025 has been entered. Claims 15, 19, 22, 24-27, 29-30, 32, 34, and 36 have been amended. Claims 31 and 35 have been cancelled.
In the Non-Final dated 5/20/2025, the specification was objected to because it contained an embedded hyperlink and/or other form of browser-executable code. Upon amendment to the specification to omit the prefix of the hyperlink, the objection has been overcome and withdrawn.
Claims 15, 17-20, 22-23, 26, 31, and 34-36 were rejected under 35 U.S.C. 112(a) in the Non-Final dated 5/20/2025. In response, Applicant has amended the claims to omit the limitation, “prodrug”, and to explicitly define the limitation of “metabolite” by the addition of structures in claim 15. Thus, the rejection is overcome and withdrawn.
In the Non-Final dated 5/20/2025, claims 15, 19-20, 22-23, and 31 were rejected under 35 U.S.C. 102(a)(1). Applicants arguments were considered, but were unpersuasive. However, upon amendment to claim 15 to recite the limitation of “where the chemotherapeutic drug is selected from a taxane drug or a protease inhibitor drug”, the 102 rejection is overcome. Doxorubicin, the chemotherapeutic drug of the reference Liao, is not a taxane or a protease inhibitor; it is an anthracycline and acts via DNA interference. Thus, the 102 rejection is withdrawn.
Claims 15, 17-20, 22-23, 26, 31, and 34-36 were rejected under 35 U.S.C. 103 in the Non-Final dated 5/20/2025. In response, Applicant argues that chemotherapeutic drug-induced peripheral neuropathy has a different pathogenesis than the metabolic neuropathy of diabetic peripheral neuropathy, and states that they develop and progress by different mechanisms and processes (page 14, 1st paragraph). However, Applicant has not provided any clarity as to the different mechanisms and processes, and has not provided evidence to refute evidentiary reference Mayo Clinic (https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/symptoms-causes/syc-20352061), which describes peripheral neuropathy as a disease of the same symptoms, regardless of pathogenesis.
Additionally, Applicant argues that because butylphthalide and duloxetine are structurally different, one of ordinary skill in the art would not expect butylphthalide to have the same properties. However, because duloxetine and butylphthalide are known to treat peripheral neuropathies, and symptoms thereof without a known mechanism of action, this argument is not considered persuasive and it would be obvious to a skilled artisan to treat peripheral neuropathies of a different pathogenesis with the same compounds. The 103 rejection is maintained. The claims were updated to reflect claim cancellations by Applicant.
Election/Restriction
Applicant’s election of the butylphthalide formulation including:
An oral formulation comprising about 1 mg to 300 mg of butylphthalide
Daily dose of about 400 mg to 800 mg as the species of dose of butylphthalide
Twice per day as the species of administration frequency
Oral formulation as the species of administration route
Duloxetine or a salt thereof as the species of other drug for treating peripheral neuropathy
Paclitaxel as the species of chemotherapeutic drug inducing the neuropathy.
with traverse in the reply filed 3/7/2025 is acknowledged. The traversal is on the grounds that the primary reference used to break unity, Wang, teaches the use of butylphthalide to treat diabetic peripheral neuropathy, a metabolic neuropathy, which has a different pathogenesis from that of the chemotherapeutic drug-induced peripheral neuropathy recited in the instant claims. Further, the secondary reference used to break unity, Lavoie Smith, teaches the use of duloxetine, an effective treatment for diabetic neuropathy, to treat chemotherapy-induced peripheral neuropathy has a different structure than that of butylphthalide. However, though diabetic peripheral neuropathy and chemotherapeutic drug-induced peripheral neuropathy may have different pathogeneses, both diabetes and chemotherapy cause nerve damage that result in the same disease: peripheral neuropathy. Evidentiary reference Mayo Clinic (https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/symptoms-causes/syc-20352061) describes peripheral neuropathy as a disease of the same symptoms, regardless of pathogenesis. Because the treatment of peripheral neuropathy in the instant specification and the prior art is merely treatment of symptoms without elucidation of the physiopathology, one of ordinary skill would readily predict that butylphthalide would treat chemotherapeutic-induced peripheral neuropathy because it treats diabetic peripheral neuropathy, and there is no recognized clinical difference between the two. See the 103 rejection below. Thus, the election of species requirement is deemed proper and FINAL.
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
In the Non-Final dated 5/20/2025, the elected species was searched and no prior art was identified that encompassed all elements (i)-(vi) of the elected species. Thus, the species was expanded to include additional administration frequencies and no additional drug for treating peripheral neuropathy. The full scope of the claims has not yet been searched in accordance with Markush search practice. Claims 15, 17-20, 22-23, 26, 34, and 36 read on the expanded species. Claims 24-25, 27-30, and 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species and/or group, there being no allowable generic or linking claim. Because the 103 rejection has been maintained, the scope of the search was not expanded in this office action.
Claim Interpretation
Claims 15 and 34 recite the phrase, “therapeutically effective”, in reference to the amount of butylphthalide administered to a subject in need thereof. According to the specification, the therapeutically effective amount refers to a daily dose from about 1 mg to 10,000 mgs orally, and 1 mg to 1,000 mgs by injection, with narrower ranges listed as preferred (paras [0028] and [0029]). The examples of administration of butylphthalide to subjects fall within the range of 1mg to 10,0000 mgs orally and 1 mg to 1,000 mgs by injection, and thus, this phrase is currently being interpreted as within the given ranges.
Claim 19 recites the term, “clinically acceptable formulation”. The definition provided in paragraph [0017] of the specification does not define the term, but does give the examples of an oral formulation, an injectable formulation, a topical formulation, or an external formulation, and preferably an oral formulation and an injectable formulation. Thus, the term is currently being interpretated as the examples provided in paragraph [0017] of the specification.
Claims 22-23 and 26 recite the term, “about”, in reference to the dosage value of butylphthalide administered to the subject. The specification defines the term in paragraph [0061] as ±10% of the numerical value, and preferably ±5% of the numerical value. The ± percentage integers from 1-10% are provided as examples. Thus, the term is currently being interpreted as the largest value ±10% to ensure the broadest reasonable interpretation of the term “about” of the instant claims.
Claims 22-23 and 26 also recite broad and narrow dosage range limitations, which according to MPEP § 2173.05(c), may render the claim indefinite when the boundaries of the claim are not discernible. However, since each range is distinctly separated by “or” logic, one of ordinary skill can identify boundary of the claim and a teaching inside any one of those ranges would meet the limitations of the claim. Currently, the broad and narrow dosage range limitations are being interpreted as alternative ranges and there is no question as to whether one is required or not since the logic is that meeting anyone of the alternatives would meet the claim limitation. Stated differently, though the instant claims recite broad and narrow dosage range limitations, the limitations do not meet the bar for a 35 U.S.C. 112(b) rejection because they are currently being interpreted as alternative ranges and any one of the alternatives would meet the claim limitation.
MAINTAINED REJECTIONS
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.
Claims 15, 17-20, 22-23, 26, 34, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Wang, M. Hebei Journal of Traditional Chinese Medicine, 2013, 24, 1209-1211, cited at the IDS of 12/2/2022) as evidenced by CSPC (https://www.e-cspc.com/details/details_96_142.html) in view of Lavoie Smith (Lavoie Smith, E. M. et. al. JAMA, 2013, 309, 1359-1367). This rejection applies to the expanded species, where the method for preventing, relieving, or treating a chemotherapeutic drug-induced peripheral neuropathy with butylphthalide can be administered at different frequencies not elected.
Determining the scope and contents of the prior art
The reference Wang teaches a method for relieving or treating diabetic peripheral neuropathy, including administering to a subject in need thereof a therapeutically effective amount of butylphthalide (page 2, section 1.3 and page 3, section 2).
With respect to claims 17-18, Wang teaches that the use of butylphthalide to treat diabetic peripheral neuropathy significantly reduces limb pain and numbness, also known to one of ordinary skill as paresthesia (page 4, last paragraph).
With respect to claims 19-20, Wang teaches a clinically acceptable formulation as an oral formulation of soft capsules (page 2, section 1.3.3).
With respect to claims 22-23 and 26, the capsules taught by Wang are of national medicine standard H20050299, which are 100 mg capsules as evidenced by the CSPC website (https://www.e-cspc.com/details/details_96_142.html). The 100 mg capsules were administered in dosages of two capsules three times per day (page 2, section 1.3.3).
With respect to claim 34, Wang teaches above and at least those teachings are incorporated herein. Additionally, the butylphthalide of Wang was administered in soft capsules, which the materials of qualify as a pharmaceutically acceptable excipient, and therefore meets the limitation of the pharmaceutical composition recited in the claim.
The reference Lavoie Smith teaches a clinical trial of the effect of duloxetine, a compound used for treatment of painful diabetic peripheral neuropathy on pain, function, and quality of life among patients with chemotherapy-induced peripheral neuropathy (title, abstract). Lavoie Smith teaches the hypothesis that because duloxetine is an effective treatment for painful diabetic neuropathy, that it would be effective for chemotherapy-induced peripheral neuropathy as well (page 1360, col 1, para [1]). The conclusion of the clinical trial states that 5 weeks of duloxetine treatment resulted in an improvement in pain in patients with chemotherapy-induced peripheral neuropathy (page 1366, col 1, para [3]). With respect to claim 36, patients in the study included patients with chemotherapy-induced pain after paclitaxel, other taxane, or oxaliplatin treatment (abstract).
Ascertaining the differences between the prior art and the claims at issue
The reference Wang fails to teach the use of butylphthalide to treat peripheral neuropathies with different causes; specifically, chemotherapy-induced peripheral neuropathy.
The reference Lavoie Smith fails to teach butylphthalide as the pharmaceutical to treat chemotherapy-induced peripheral neuropathy.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods of treatment of peripheral neuropathy. An artisan possesses the technical knowledge necessary to make adjustments to the methods of treatment to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to compounds of said methods of treatment of peripheral neuropathy and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (B), it would have been prima facie obvious to substitute the disease of diabetic peripheral neuropathy of Wang with the disease of chemotherapy-induced peripheral neuropathy of Lavoie Smith because Lavoie Smith teaches that chemotherapy-induced peripheral neuropathy is treatable with the same compounds as diabetic peripheral neuropathy, and Wang teaches butylphthalide can successfully treat diabetic peripheral neuropathy. One of ordinary skill in the art would be motivated before the effective filing date to treat chemotherapy-induced peripheral neuropathy with butylphthalide because it is known to treat diabetic peripheral neuropathy. A skilled artisan would have readily predicted that the treatment of chemotherapy-induced peripheral neuropathy with butylphthalide would be successful in light of the teachings of Wang and Lavoie Smith.
Conclusion
Claims 15, 17-20, 22-23, 26, 34, and 36 are rejected. Claims 24-25, 27-30, and 32-33 are withdrawn.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights