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 Acknowledgments are made that this application claims the priority to the following: . Information Disclosure Statement The information disclosure statement s (IDS) comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits. 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 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 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. 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 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 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Chiaretti ( WO2018/087656A1 ; see applicants filed IDS on 09/22/2023 ) in view of Imbimbo (WO 2019/207106 A1) , Lewin (European Journal of Neuroscience, vol.6, pp 1903-1912, 1994) and Liu (Journal of Hainan Medical University, 2017, 23(7), 113-117) . For claim 1 : Chiaretti teaches a method for treating traumatic brain injury by means of intranasal administration of nerve growth factor (NGF) or molecules with NFG-like activity [see A bstract and S ummary of I nvention and Claims ]. Differences between Chiaretti and instant claim(s) are as follows: (i) Chiaretti silent on applicants SEQ ID NO:1. (ii) Chiaretti silent on subjecting the mammalian subject to hypothermia. With regard to (i) of above, Imbimbo teaches mature NGF or therapeutically active mutein, represented by SEQ ID NO:2, wherein proline at 61 is substituted by serine and arginine at position 100 is substituted by glutamic acid [see Fig.15C, pages 7-8 , and claims ] and, so, the SEQ ID NO:2 with these substitutions, is identical to applicants SEQ ID NO:1. The sequence of Imbimbo is interpreted as a peptide with NFG-like activity and so, a skilled person in the art would be motivated to replace NGF in the teachings of Chiaretti and arrive at applicants method with a reasonable expectation of success. A skilled person would prefer sequence of Imbimbo because it does not have undesirable amino acid sequence. With regard to (ii) of above, the reasoning from the teachings of following art cures this deficiency: Lewin teaches that the heat hyperalgesia that follows NGF administration is very rapid, being apparent within 10 min of the injection [see Abstract and Introduction]. So, excess heat is inflammatory in nature and can cause undesirable effects. It is common sense to apply cold pad to lower or relieve the pain. Therefore, a skilled person in the art would be motivated to lower the thermal effect, such as subject to hypothermia. Liu teaches that mouse nerve growth factor combined with early mild hypothermia therapy can protect the brain function and inhibit the systemic inflammatory and stress reaction in patients with severe craniocerebral injury [see Abstract an Discussion] . Therefore, a skilled person in the art would be motivated to combine hypothermia in the teachings of Chiaretti and arrive at applicants method with a reasonable expectation of success. For claim 2 : Chiaretti teaches 0.05 to 0.4 mg of NGF or molecule with NGF-like activity per kg of subject [see claim 5]. Generally, concentrations of components for a given process is considered as result effective variables, and the differences in their amounts will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such differences in result-effective variables are 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). 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. For claim 3 -6 : Chiaretti teaches treating brain ischemic hypoxic lesions by administering NGF to a human patient intranasally [see claim 1 and 9 ] , and wherein said daily doses divided in 1 to 5 aliquots and one or more daily doses are administered for one or more therapeutic cycle [see claims 6-8] . For claim 7 -12 : Chiaretti teaches 0.05 to 0.4 mg of NGF or molecule with NGF-like activity per kg of subject [see claim 5]. For claim 13 : It is common sense to apply a drug to treat a wound or lesion, as soon as possible. This limitation is trivial. For claim 14 : Chiaretti silent on acetate buffer . However, Imbimbo teaches acetate buffer [see page 112, for example]. For claims 15-17 : Chiaretti silent administering hypothermia. As explained above, under For claim 1 , Lewin teaches that the heat hyperalgesia that follows NGF administration is very rapid, being apparent within 10 min of the injection [see Abstract and Introduction]. Therefore, it is desirable to administer hypothermia as quickly as possible after the injury and can be administered for a desirable length of time. For claims 18-19 : Suitable temperature and time can be achieved through a routine experimentation, and so, this limitation is obvious. For claims 20-21 : Chiaretti teaches 0.05 to 0.4 mg of NGF or molecule with NGF-like activity per kg of subject [see claim 5]. Generally, concentrations of components for a given process is considered as result effective variables, and the differences in their amounts will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such differences in result-effective variables are 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). 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. With regard to temperature, s uitable temperature and time can be achieved through a routine experimentation, and so, this limitation is obvious. Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components and their use in treating traumatic brain lesion or brain ischemic hypoxic lesion , were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. The motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success. The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker , 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT SUDHAKAR KATAKAM whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-9929 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 8:30 am to 5 pm . 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, FILLIN "SPE Name?" \* MERGEFORMAT Melissa Fisher can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-7430 . 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. / SUDHAKAR KATAKAM/ Primary Examiner, Art Unit 1658