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 Pursuant to the preliminary amendment dated 7/19/2023, claims 12-16, 18, 19, 24, 26, 29-38, 40 and 41 are cancelled and claims 17, 23, 27 and 39 are amended. No claims are newly added. Claims 1-11, 17, 20-23, 25, 27 , 28 and 39 are pen ding in the instant application and are examined on the merits herein. Priority The application is a National Stage entry of PCT/US2022/012993 filed on 1/19/2022 , which claims priority to provisional application 63/139057 filed on 1/19/2021. Information Disclosure Statement The information disclosure statement (IDS) dated 2/5/2024 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609, except where noted. Accordingly, the I DS ha s been placed in the application file and the information therein has been considered as to the merits. Claim Objection s Claims 2, 9, 20 , 25 , 27 and 28 are objected to for grammatical or formatting errors . Claim 2 recites, “…GD3 as administered…”, which should read, “…GD3 is administered…”. Claim 9 recites, “…administered alone or in the absence of GM1.”, which should read, “…administered alone and in the absence of GM1.” . Claim 20 recites, “…the subject comprises a disease…”, which should read, “…the subject suffers from a disease…”. Claim 25 recites, “…formation of or existing…”, which should read, “…formation of existing…”. Claim 27 recites “A method of claim 11…”, which is of improper form because “A method” indicates an independent claim, but “of claim 11”, indicates a dependent claim. Appropriate correction is required. Claim 28 is objected to for depending from claim 27 . C laim Rejections - 35 USC § 112 (b) 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. Claim s 5-7 and 39 are rejected 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. Claim 5 recites the acronym “NSCs”, which is not defined in claim 5 or any base claim. While some acronyms are known to those or ordinary skill in the art, even those well-known acronyms may have multiple meanings. Furthermore, practitioners routinely define their own acronyms, which are not commonly known to those of ordinary skill in the art. Therefore, an acronym absent a definition renders a claim indefinite. Claims 6 and 7 are indefinite for depending from claim 5. Claim 39 recites the preamble “A dosage unit” which indicates that the claim is directed to a composition of matter, but the claim further recites “according to the method of claim 1 ” , which indicates that the claim is directed to a method of treatment. The metes and bounds of claim 39 are unclear because a claim can only be directed to a single statutory category of invention. Claim Rejections - 35 USC § 112 (d) 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. Claim s 7, 27 and 28 are rejected under 35 U.S.C. 112(d) , a s 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. Claim 7 recites that administration of GD3 and GM1 may be concurrent. However, claim 7 depends ultimately from claim 4, which requires that GD3 is administered prior to GM1. Claim 4 does not allow for concurrent administration, thus claim 7 does not properly further limit claim 4. FILLIN "Insert an explanation of what is in the claim and why the claim does not contain a further limitation or identify which limitation of the claim upon which it depends is missing." \* MERGEFORMAT Claim 27 recites that the mode of administration is to the eye of the subject. However, claim 27 depends ultimately from claim 1, which requires that the administration is intranasal. Thus, claim 27 does not further limit claim 1. Claim 28 is rejected for depending from claim 27. 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. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim s 1, 3, 8, 10, 11 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schneider et al. (WO 2011/028799 A1, PTO-892) . Schneider et al. discloses a method for treating or preventing the neurodegenerative condition, Parkinson’s disease, by intranasally administering ganglioside GM-1. (¶ 0011, 0029; Claim 30) Schneider also teaches that i n addition to Parkinson's disease therapy as disclosed herein the c omposition and method may be used to treat a variety of neurodegenerative disorders including, without limitation: any disease amenable to treatment by administration of GM 1 ; Parkinson's-like dementia, Huntington's Disease; Huntington's-type dementia; and Alzheimer's disease. (ibid) Schneider further discloses that the administration may be performed using a single dose nasal dispenser. (Claim 31) With respect to claim 3 and the recitation, “to increase neuronal differentiation”, this limitation is not accorded patentable weight because of the inseparable connection between an administered composition and the mechanism of action within the subject to which the composition is administered. The active method step in the instant claim is administering GM1 to a subject with a neurodegenerative condition, whereas “to increase neuronal differentiation” is an effect which will necessarily occur and does not delineate a manipulative difference between the instant method and the method of the prior art. Therefore, because the combined prior art teaches the same active step to administer the same composition, the properties applicant discloses and/or claims are necessarily present. Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) . See also MPEP § 2112.02. Accordingly, the instant claims are anticipated by the prior art. 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. 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. 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. Claim s 1, 3, 8, 10, 11, 17, 23 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Sipione et al. (US 2012/0283199, IDS) . Sipione et al. discloses a method for treating a subject suffering from, or susceptible to, or delaying the onset of, or treating a symptom of, Huntington’s disease, by administering ganglioside GM1. (Claims 123, 131) Sipione discloses that Huntington’s disease symptoms include schizophrenia. (¶0055) Sipione teaches that neurons are dysfunctional in Huntington’s and that treatment with GM1 improves neuron performance. (Abstract; ¶0004, 0186, 0192) Sipione also teaches that administration may be pulmonary administration , by use of an inhaler or nebulizer, and formulation with an aerosolizing agent, by inhalation or insufflation of powders or aerosols, including by nebulizer (intratracheal, intranasal, epidermal and transdermal). (¶0066) Sipione et al. does not exemplify or claim intranasal administration of GM1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that intranasal administration of GM1 would be a functionally equivalent means of active agent delivery because Sipione specifically suggests that intranasal administration is among the envisioned routes of GM1 delivery. With respect to claim 3 and the recitation, “ to increase neuronal differentiation ”, this limitation is not accorded patentable weight because of the inseparable connection between an administered composition and the mechanism of action within the subject to which the composition is administered. The active method step in the instant claim is administering GM1 to a subject with a neurodegenerative condition, whereas “to increase neuronal differentiation” is an effect which will necessarily occur and does not delineate a manipulative difference between the instant method and the method of the prior art. Therefore, because the combined prior art teaches the same active step to administer the same composition, the properties applicant discloses and/or claims are necessarily present. Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) . See also MPEP § 2112.02. With respect to claim 17, Sipione teaches that among the symptoms of Huntington’s disease envisioned to be treated is schizophrenia, thereby meeting the claimed limitation. With respect to claim 39, the suggestion of Sipione of the use of an inhaler for intranasal administration meets the limitation of a “dosage unit”. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim s 1-3, 10, 11 , 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892), in view of Itokazu et al. (ASN Neuro., 2019, IDS) . The disclosure of Schneider is referenced as discussed above. Schneider does not teach administering ganglioside GD3. Itokazu et al. discloses that administration of gangliosides GD3 and GM1 simultaneously could enhance neurogenesis in adult mouse brain. For promoting adult hippocampal neurogenesis, GD3 restored neural stem cell ( NSC ) pools and that GM1 enhanced neuronal differentiation at DG of AD model mouse brain. We have reported that the GD3 containing microdomains initiate and facilitate the EGF signaling in cultured NSCs. We have also reported that GM1 promotes neuronal differentiation by an epigenetic regulatory mechanism. Further studies are in progress to determine whether injection of specific gangliosides, such as GD3, GM1, and their analogs, could represent a novel and effective adjuvant strategy for the treatment of AD, Parkinson’s disease, and related neurodegenerative diseases by promoting adult neurogenesis. (p. 6, Col. 1-2) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Schneider to intranasally administer a combination of GM1 and GD3, to treat Parkinson’s disease via restor ation of NSC pools and enhanc ing neuronal differentiation , thereby arriving at the instant invention. One would be motivated to modify Schneider in this manner because Itokazu teaches that the combination of GM1 and GD3 is effective to restor e NSC pools and enhanc e neuronal differentiation , in a mouse model of neurodegeneration. Itokazu also suggests that the administration of GM1 and GD3 in combination could be effective to treat Parkinson’s disease, which is directly in line with the goal of Schneider. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim s 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892), in view of Itokazu et al. (ASN Neuro., 2019, IDS), further in view of Wilkinson (Pharmacokinetics, 2001, PTO-892 ) . The disclosure of Schneider /Itokazu is referenced as discussed above. The combined prior art does not teach administering GD3 prior to GM1 . Wilkinson teaches that following administration of a dose of a drug, its effects usually show a characteristic temporal pattern (p. 24, column 2, last paragraph). The intensity of a drug’s effect is related to its concentration above a minimum effective concentration, whereas the duration of this effect is a reflection of the length of time the drug level is above this value (p. 25, column 1). These considerations, in general, apply to both desired and undesired drug effects and, as a result, a therapeutic window exists reflecting a concentration range that provides efficacy without unacceptable toxicity (p. 25, bridging paragraph). Wilkinson further teaches that similar considerations apply after multiple dosing associated with long-term therapy; therefore they determine the amount and frequency of drug administration to achieve an optimal therapeutic effect (p. 25, column 2). It is noted that Wilkinson does not teach whether drugs in a combined treatment should be administe red separately, admixed, at the same time or at different times . However, the same principles of a therapeutic window reflective of the effective concentration of the drug still apply. I t would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Schneider/Itokazu with the teachings of Wilkinson, regarding a drug’s effect and therapeutic window. It would have been prima facie obvious for one of ordinary skill in the art to use the information taught by Wilkinson, regarding a drug's therapeutic window, to determine whether a combined treatment using multiple drugs should be administered separately, admixed, at the same time or at different times . Furthermore, one of ordinary skill in the art would know that in order to attain the benefits of a combined drug treatment, both drugs must be present together at some point in the body, particularly if a synergistic effect is desired. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892), in view of Itokazu et al. (ASN Neuro., 2019, IDS), further in view of Wang et al. (PNAS, 2013, IDS) . The disclosure of Schneider/Itokazu is referenced as discussed above. The combined prior art does not teach administering GD3 alone . Wang discloses that GD3 plays an important role in maintenance of neural stem cells (NSCs) self-renewal capability by preserving the EGFRs from degradation and by facilitating their recycling to the membrane surface. (p. 19138, ¶1) I t would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of Schneider/Itokazu could be modified to administer GD3, in the absence of GM1, thereby arriving at the instant invention. Modifying the combined prior art in this manner would reasonably be expected to treat a neurodegenerative condition because Wang teaches that GD3 by itself is effective to increase the proliferation of NSCs and Itokazu teaches that increasing the proliferation of NSCs is correlated with promoting adult neurogenesis in damaged brain for disease treatment . Thus, the combined teachings of Schneider/Itokazu/Wang reasonably suggest that exogenous administration of either GM1, GD3 or a combination of GM1+GD3, would reasonably be expected to treat a neurodegenerative disease or condition. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892), in view of Frey et al. (US 2006/0030542 A1, PTO-892) . The disclosure of Schneider is referenced as discussed above. Schneider does not teach treating a disease or injury of the eye. Frey discloses methods of treating diseases, including Parkinson’s, by intranasally administering GM1. (Claim 104, 113) Frey also discloses that the treatment method is effective for treating dry eye syndrome. (¶0044, 0087, 0091) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of Schneider could also be used to treat dry eye disease , thereby arriving at the instant invention . One would be motivated to modify Schneider in this manner because Frey suggests that intranasal administration of Gm1 can be used to treat Parkinson’s or dry eye disease. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim s 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892). The disclosure of Schneider is referenced as discussed above. Schneider further discloses that GM1 administration may be effective to treat traumatic brain injury. (¶0010) Schneider also discloses that the administration of GM1 acts as a neuroprotective agent. (¶0029, 0039) With respect to claim 21, i t would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that one could use GM1 intranasal administration to treat TBI because Schneider specifically suggests that GM1 would be effective to treat TBI. With respect tot claim 23, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the intent of a neuroprotective agent is to pre-emptively treat a subject that is susceptible to a neurodegenerative condition, prior to actual damage being done. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892), in view of Stamford et al. (US 2011/0110957, PTO-892) . The disclosure of Schneider is referenced as discussed above. Schneider does not teach olfactory impairment. Stamford discloses that olfactory impairment is known to be associated with Parkinson’s disease. (¶0003) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of Schneider would be effective to treat olfactory impairment associated with Parkinson’s disease, thereby arriving at the instant invention . One would find this obvious because Schneider is directed to treating Parkinson’s disease and by successfully treating the condition underlying the associated condition of olfactory impairment, one would reasonably expect the olfactory impairment to be treated as well. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2011/028799 A1, PTO-892), in view of Ledeen et al. (Prog. Mol. Bio. Trans. Sci., 2018, PTO-892) . The disclosure of Schneider is referenced as discussed above. Schneider does not teach reducing formation of amyloid or alpha-synuc l ein aggregates. Ledeen et al. discloses the treatment with exogenous GM1 in a Parkinson’s disease model resulted in improvement in motor function and reduction in formation of alpha-synuclein aggregates. (Abstract) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of Schneider would result in reduction in formation of alpha-synuclein aggregates, thereby arriving at the instant invention . One would find this obvious because both Schneider and Ledeen are using GM1 administration to treat the same disease. Accordingly, the instant claims are prima facie obvious over the teachings of the prior art. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DALE R MILLER whose telephone number is (571) 272-6146. The examiner can normally be reached on M-F 7:00 AM – 3:30 PM EST. 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, Scarlett Goon can be reached on (571) 270-5341 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from Patent Center and the Private Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from Patent Center or Private PAIR. Status information for unpublished applications is available through Patent Center and Private PAIR to authorized users only. Should you have questions about access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /DALE R MILLER/ Primary Examiner, Art Unit 1693