CTNF 18/605,320 CTNF 100710 DETAILED ACTION 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Status of the Claims Claims 1-3, 5-11, 13-19, 22, 26, and 28 are pending. Claims 4, 12, 20, 21, 23-25, 27, and 29-49 are cancelled. Status of Priority The present application is a continuation of U.S. Application No. 17/342,117, which was filed on June 8, 2021, which is a continuation of U.S. Application No. 16/557,028, which was filed on August 30, 2019, which claims the benefit of the filing date of U.S. Provisional Application No. 62/725,484, which was filed on August 31, 2018, and Indian Application No. 201821021206, which was filed on September 6, 2018. It is noted here that Examiner could not locate a certified copy of the foreign priority document. Specification - Abstract Applicant is reminded of the proper content of an abstract of the disclosure. In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class . 06-16 AIA Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length . The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. Specification - Disclosure The specification is objected to for the following informalities: On pg. 21, line 7, “tween-80” (i.e., a trademarked good) is listed as one of the alternatives for a pharmaceutically acceptable excipient and carrier. For clarity, “tween-80” should be referred to by its generic name. Please ensure that all trademarked goods listed in the specification are referred to by their generic name. Appropriate correction is required. 06-31 AIA The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. Drawings 06-22 AIA The drawings are objected to because of the following reasons: The instant specification indicates that in Fig. 3A, “[g]reen lines represent initial scratch front, yellow is scratch front after respective treatment time” (pg. 3, lines 18-19). However, the figures as submitted are not in color, and the referenced green and yellow lines are not discernible in grayscale. Accordingly, the Examiner notes that the figures should be revised such that all elements, including those originally depicted in color, are clearly distinguishable when reproduced in grayscale. In Fig. 3B, the text is not clearly legible due to its low resolution and size. Accordingly, the Examiner requests that the figure be revised to improve clarity such as by increasing the size or resolution of the image. Applicant is requested to review all figures and revise them as necessary to ensure that all features are clear and readily legible. Appropriate correction is required . Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Rejections - 35 USC § 112(a) – Written Description 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. 07-31-01 Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph , as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 14 recites, “wherein the amount of SCNE is about 50 mg to 75 mg.” According to the instant specification: “In some aspects, the composition can comprise SNCO 2 extract: 75 mg;” Pg. 11, line 19 “In some aspects, the composition can comprise SNCO 2 extract: 50 mg;” Pg. 11, line 22 In other words, the instant specification only states that the amount of SCNE is either 50 mg or 75 mg, not a range from 50 mg to 75 mg. Thus, claim 14 is rejected for failing to comply with the written description requirement. Claim Rejections - 35 USC § 112(b) 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 2, 3, and 14 are rejected 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. 07-34-10 Regarding claim 2, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). 07-34-10 In claim 2, the phrase "such as" further renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). 07-35-01 AIA Claim 2 contains the trademark/trade name “tween-80.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a pharmaceutically acceptable excipient and, accordingly, the identification/description is indefinite. 07-34-03 The term “about” in claims 3 and 14 is a relative term which renders the claims indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Although the specification provides a general discussion of the term “about” (see pg. 6, lines 28-34 and pg. 7, lines 5-8), it fails to indicate what range of values outside the explicitly recited endpoints would be included. As such, a POSITA would not be able to determine, with reasonable certainty, the metes and bounds of the claimed subject matter. Claim Rejections - 35 USC § 112(d) 07-36 AIA The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. 07-36-01 AIA Claim s 6 and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph , as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. A dependent claim must further limit the subject matter of the claim from which it depends. Claim 1 requires that the supercritical CO 2 neem extract comprises nimbolide, nimbin, and salanin, whereas claims 6 and 16 recite that the SCNE comprises one or more limonoids. Since “one or more limonoids” encompasses embodiments having fewer than the three specific limonoids recited in claim 1, claim 6 does not further limit and instead broadens the scope of claim 1. Therefore, claims 6 and 16 are rejected as being of improper dependent form. According to the following references, nimbolide, nimbin, and salannin are all limonoids: Simmonds et al. (Simmonds, M. S. J. et al. Pest Manag Sci 2004 , 60, 459-464.; see abstract) Patel et al. (Patel) (Patel, M. J. et al. Molecular Carcinogenesis 2018 , 57, 1156-1165.; published April 26, 2018.; abstract) Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Note on 35 USC § 102 and § 103 Rejections 07-06 AIA 15-10-15 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. Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. Rejection Part 1: 07-21-aia AIA Claim s 1, 6, 13, 16, 22, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over : Patel et al. (Patel) (Patel, M. J. et al. Molecular Carcinogenesis 2018 , 57, 1156-1165.; published April 26, 2018.) in view of Johnson et al. (Johnson) (Johnson, S. et al. Phytochemical Analysis 1997 , 8, 228-232.) Patel teaches the following (see pg. 1160, section 3.6): A xenografted mouse model bearing a tumor derived from HCT116 cell line HCT116 cell line is made up of human colon cancer cells (see Patel, abstract) The xenografted mouse models were fed either a control diet or one of two diets comprising 200 or 400 mg/kg of supercritical CO 2 neem extract (SCNE). It was found that the SCNE diet significantly reduced HCT116 tumor volume. “To understand the role of dietary SCNE [Patel] measured circulating cytokines in the serum after the respective SCNE treatment. In the HCT116 tumor bearing animals, the pro-inflammatory cytokine levels (TNFα, IL-1a, IL-1b, IL-6) were markedly reduced by SCNE. [Patel] also showed strong reduction in several chemokines (MCP-1, MIP-1a), immunomodulatory cytokines (GCSF, GMCSF, IFNγ, IL-2, IL-3, IL-10), and the pro-angiogenic IL-17” (pg. 1160, left col., section 3.6, last three sentences). Patel also teaches: Both SCNE and nimbolide treatment in HCT116 and HT29 cells resulted in decreased expression of anti-apoptotic marker Bcl-2 protein and upregulation of pro-apoptotic marker Bax protein in both types of cells lines (pg. 1159, section 3.2, 1 st paragraph, last sentence.) “…treatment of CRC [i.e., colorectal cancer] cell lines with SCNE and nimbolide remarkably decreased the expression of IL-6 and TNF-α protein from total cell lysate” and that “treatment of SCNE and nimbolide decreased the protein expression of COX1 in CRC cell lines” (pg. 1159, section 3.4, 2 nd and 3 rd paragraphs). The above two points show that SCNE and nimbolide have an anti-inflammatory effect on CRC cell lines Patel does not disclose the contents of SCNE. Johnson is relied upon for this disclosure. Johnson discloses that supercritical CO 2 can extract all nimbin and salannin from neem seeds and some azadirachtin (abstract). Therefore, Johnson teaches that a supercritical CO 2 neem extract comprises at least nimbin, salannin, and azadirachtin. Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention, to utilize a supercritical CO 2 neem extract comprising known neem limonoids, including nimbin and salanin, in combination with nimbolide (also a limonoid found in neem) for the treatment of colon cancer. Patel provides motivation by demonstrating that both SCNE and nimbolide independently exhibit anticancer and anti-inflammatory activity in relevant in vitro and in vivo models , including reduction of tumor growth and suppression of inflammatory cytokines. A POSITA would have reasonably expected that SCNE, known to contain limonoids, would include such compounds and that their combined presence would also contribute to the observed therapeutic effects as discussed above. Furthermore, Patel’s demonstration of efficacy in xenograft mouse models, which are commonly used as predictive preclinical models for human cancer therapy (see abstract of: Jung, J. Toxicol. Res. 2014 , 30, 1-5.), would have provided a reasonable expectation of success in applying such treatment methods to human subjects. Accordingly, it would have been obvious to administer a composition comprising SCNE containing limonoids such as nimbin and salanin, together with nimbolide, to a human subject for: the treatment of colon cancer, the reduction of at least one inflammatory cytokine in serum of a human subject with colon cancer, and the reduction of inflammation in a human subject with colon cancer. Thus, claims 1, 6, 13, 16, 22, 26, and 28 are rendered obvious. Rejection Part 2: 07-21-aia AIA Claim s 2, 7-10, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over : Patel et al. (Patel) (Patel, M. J. et al. Molecular Carcinogenesis 2018 , 57, 1156-1165.; published April 26, 2018.) in view of Rowe ( Handbook of Pharmaceutical Excipients , 5 th ed.; Rowe, R. C.; Sheskey, P. J.; Owen, S. C.; Pharmaceutical Press, 2006.) and Gibson ( Pharmaceutical Preformulation and Formulation , 2 nd ed.; Gibson, M.; Informa Healthcare, 2009.) The teachings of Patel as they apply to claims 1, 6, 13, 16, 22, 26, and 28 are as discussed in “ Rejection – Part 1 ” of this section (“ Claim Rejections - 35 USC § 103 ”) and incorporated herein. Patel does not disclose a composition comprising nimbolide, nimbin, salannin, and any of the pharmaceutically acceptable excipients listed in claim 2, one or more tocopherols (such as those listed in claims 8 and 17), sesame oil, and/or aerated or fumed silica. Rowe and Gibson are relied upon for the disclosure of the properties of pharmaceutical excipients. Rowe discloses the properties of alpha-tocopherol (pg. 32-35), vitamin E (pg. 33, right col., section “17 Related Substances”, subsection “ d- Alpha tocopherol”), gamma-tocopherol (pg. 34, right col.), and sesame oil (pg. 646-648) along with other compounds for use as pharmaceutical excipients. Gibson discloses fumed silicon dioxides as “the most effective glidants” (pg. 390, line 3). Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to formulate the SCNE composition with pharmaceutically acceptable excipients such as one or more tocopherols, sesame oil, and fumed silica. As set forth by Rowe: “the beta, delta, and gamma tocopherols are considered to be more effective as antioxidants” (pg. 32, right col., lines 1-2) and “tocopherols are of value in oil- or fat-based pharmaceutical products and are normally used in the concentration range 0.001-0.05% v/v” (pg. 32, right col., lines 5-7). Sesame oil is commonly used as a solvent in the preparation of oil-soluble drug substances and may be used as a solvent in the preparation of oral capsules (pg. 646, section 7 “Applications in Pharmaceutical Formulation or Technology”). As stated above, Gibson discloses fumed silicon dioxides as “the most effective glidants” (pg. 390, line 3). The selection of such excipients for their known functions would have been a matter of routine formulation optimization to improve stability, solubility, and delivery of the active ingredient, SCNE. Thus, claims 2, 7-10, 17, and 18 are rendered obvious . Allowable Subject Matter 12-151-08 AIA 07-43 12-51-08 Claim s 5, 11, 15, and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion Claims 1-3, 6-10, 13, 14, 16-18, 22, 26, and 28 are rejected. Claims 5, 11, 15, and 19 are objected to. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM 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, JEFFREY H. 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. 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. /KRISTEN W ROMERO/Examiner, Art Unit 1624 /JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624 Application/Control Number: 18/605,320 Page 2 Art Unit: 1624 Application/Control Number: 18/605,320 Page 3 Art Unit: 1624 Application/Control Number: 18/605,320 Page 4 Art Unit: 1624 Application/Control Number: 18/605,320 Page 5 Art Unit: 1624 Application/Control Number: 18/605,320 Page 6 Art Unit: 1624 Application/Control Number: 18/605,320 Page 7 Art Unit: 1624 Application/Control Number: 18/605,320 Page 8 Art Unit: 1624 Application/Control Number: 18/605,320 Page 9 Art Unit: 1624 Application/Control Number: 18/605,320 Page 10 Art Unit: 1624 Application/Control Number: 18/605,320 Page 11 Art Unit: 1624 Application/Control Number: 18/605,320 Page 12 Art Unit: 1624 Application/Control Number: 18/605,320 Page 13 Art Unit: 1624 Application/Control Number: 18/605,320 Page 14 Art Unit: 1624
Prosecution Insights