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 the First Office Action on the Merits of US 18/264,542 filed on 08/07/2023 which is a 371 of PCT/US2022/015818 filed on 02/09/2022 which claim US priority benefit of US Provisional 63/147,509 filed on 02/09/2021. The Filing Receipt filed on 10/31/2023 is controlling.
Claims 1-19 and 27 are pending.
Election/Restrictions
Applicant’s election without traverse of invention Group II (e.g., claims 15-19) in the reply filed on May 11, 2026 is acknowledged.
Applicant’s election without traverse of Species of SEQ ID NO: 1 (i.e., from among SEQ ID Nos 1,and 3-8) in the reply filed on May 11, 2026 is acknowledged.
Claims 1-14 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 11, 2026.
Claims 15-19 are under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/147,509 filed on 02/09/2021, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Regarding claim 17, the ‘509 does not disclose the concept that the patient has decreased synaptic transmission or decreased physiological level of SYN1 (aka Synapsin 1), PSD95, VGLUT1, Gephyrin, or VGAT. The ‘509 recites Synapsin 1, PSD95, and VGLUT but does not recite VGLUT1, Gephyrin, or VGAT.
Claim 17 receives an effective filing date of 02/09/2022.
Claims 15-16 and 18-19 receive an effective filing date of 02/09/2021.
Information Disclosure Statement
The IDS statements filed on 03/13/2025 and 08/07/2023 have been considered by the examiner.
Drawings
The drawings are objected to because the text of FIG 24A, D, F, H, and J is unclear. 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 Objections
Claim 17 is objected to because of the following informalities: The abbreviated terms SYN1, PSD95, VGLUT1, Gephyrin, and VGAT should be written in full-length terms the first time they appear in the claims.
Appropriate correction is required.
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 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Stein et al (US2011/0306579, published 12/15/2011), in view of Dolotov et al “Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotropic factor protein in rat basal forebrain” (J Neurochem, 01/30/2006), in view of Castaigne et al (US 2015/0174267 published June 25, 2015), in view of Aragao et al in “Early defects in mucopolysaccharidosis type IIIC disrupt excitatory synaptic transmission” (biRXiv 07/06/2020; IDS REF), in view of Villani et al “Cytokines, neurotrophins, and oxidative stress in brain disease from mucopolysaccaridosis IIIB” (J Neurosci Res, 11/30/2006, Vol 85, pages 612-622; IDS ref).
Regarding claim 15, Stein et al discloses a method for treating a neuropathophysiological condition in a patient in need thereof by administering to the patient an effective amount of a combination of neuroprotective agents which include neuroprotective hormones, BDNF and Semax. (See para 0432; 0451; 0455; 0457-0459). As evidenced by Dolotov et al, the neuroprotective agent Semax is the therapeutic heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) which is identical to instant SEQ ID NO:1. (See Dolotov et al: Abstract, page 82, left col., first para, entire article.) Dolotov et al teaches that the Semax is an analogue of the peptide hormone adrenocorticotropin (4-10) which is also known as the corticotropin hormone ACTH. Dolotov et al teaches the heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) exerts marked neuroprotective effects and specifically that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF), which is a potent modulator of synaptic plasticity. (See Abstract, entire article). In addition, regarding claim 15, Stein et al disclose administration of neuroprotective agents may be nasally. (See para 0486; 0535; 0557; ref claim 18) Also, Dolotov et al explicitly disclose intranasal application of Semax. (Abstract, lines 1-5).
Stein et al differs from claim 15 in that they do not teach administration of the neuroprotective agents for treating a neurological mucopolysaccharidosis (MPS).
Castaigne et al discloses a method for treating a neurological mucopolysaccharidosis (MPS) including MPS-IIIA (Sanfilippo syndrome A), MPS-IIIB (Sanfilippo syndrome B), and MPS-IIIC (Sanfilippo syndrome C), in a patient in need thereof. (See para 0007; 0028; 0287 Table 2.) Castaigne et al disclose intranasal administration to the MPS patient an effective amount of BDNF by administering a polypeptide-transport vector conjugate to the subject in a therapeutically effective amount. (See para 0007; 0270-0271) Castaigne et al disclose that in certain embodiments, the disorder or disease is amenable to treatment with brain-derived neurotrophic factor (BDNF)). (See Table 2; para 0287; ref claim 21 & 26.)
Regarding claim 16, Stein et al discloses a method for treating neuropathophysiological condition in a patient in need thereof by administering to the patient an effective amount of an agent that increases the biological activity of brain-derived neurotrophic factor (BDNF) but does not explicitly disclose that the patient has decreased biological activity or physiological level of brain-derived neurotrophic factor (BDNF) as compared to a healthy subject. Villani et al is in the art of neurological MPS (Abstract) and teaches a subject with decreased biological activity or physiological level of brain-derived neurotrophic factor (BDNF) as compared to a healthy subject (Pg. 615, right-hand column, last paragraph-Pg. 616, left-hand column, first paragraph, The brains were collected from 7-month-old MPS IIIB and age-matched normal mice, and RNA was isolated for the microarray analysis Among the expressed genes, only those with a -fold change > 1.5 were considered significantly altered and reported in Table 1; wherein Table 1 includes gene symbol/name BDNF/Brain-derived neurotrophic factor, -Fold change 0.51).
Regarding claim 17, Stein et al does not explicitly disclose that the patient has decreased synaptic transmission or decreased physiological level of SYN1, PSD95, VGLUT1, Gephyrin, or VGAT. Aragao et al disclose that early defects in lysosomal storage diseases such as MPSIII disrupt synaptic transmission. Aragao et al disclose the study of synaptic spines of mouse models for MPS IIIC and also studied postsynaptic densities in post-mortem corticies of human neurological MPS patients. Aragao et al disclose a subject with decreased synaptic transmission or decreased physiological level of SYN1, PSD95, VGLUT1, Gephyrin, or VGAT (Pg. 26, first paragraph.) Aragao et al disclose that they performed proteomic analyses of mouse brain synaptosomes. Synaptosomes were isolated from three MPS IIIC and three WT mice at 3 and 6 months of age, and their protein content analyzed; Pg. 27, first paragraph, Syn1 was 29.8% lower at 3 months (WT=22.3±7.2; MPS IIIC=15.7±5.5) and reached 41.5% reduction by the age of 6 months (WT=39.3±0.6; MPS IIIC=23±1.7).
Regarding claim 18, Castaigne et al discloses monitoring the treatment of MPS by checking the level of BDNF in the patient. Dolotov et al teaches the heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) exerts marked neuroprotective effects and specifically that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF), which is a potent modulator of synaptic plasticity. (See Abstract, entire article). Dolotov et al teaches monitoring BDNF levels after administration of Semax (i.e., the peptide of instant SEQ ID NO:1).
Regarding claim 19, Castaigne et al discloses wherein the patient suffers from MPS III (See para 0287). Aragao et al disclose the study of synaptic spines of mouse models for MPS IIIC.
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art having the cited references before the effective filing date would have been motivated to combine the elements of the cited references for the rationale of treating MPS III in a patient. First, Stein et al disclose Semax as a neuroprotective agent for treating a patient in need. Dolotov et al teach that Semax is the therapeutic heptapeptide of instant SEQ ID NO: 1. and exerts marked neuroprotective effects and specifically that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF) which is a potent modulator of synaptic plasticity. (See Abstract, entire article). Dolotov et al teaches monitoring BDNF levels after administration of Semax for the rationale that stimulation of BDNF is a cause for the neuroprotective effects caused by administering Semax (i.e., the peptide of instant SEQ ID NO:1). Further, regarding claim 17, one of ordinary skill in the art would have been motivated to select a subject with decreased synaptic transmission or decreased physiological level of SYN1, PSD95, VGLUT1, Gephyrin, or VGAT for the rationale of Aragao et al to select a patient with neurological MPS prior to treatment and then to follow effects of such treatment.
It would have been obvious to one of ordinary skill in the art at the time of the invention to do such because the references are in the field of treating neurodegenerative diseases related to adding/increasing BDNF, including MPS III, by administering therapeutic agents, specifically agents related to adding/increasing BDNF in a patient.
In view of the high skill level in the art before the effective filing date of the presently claimed invention it is considered that one of ordinary skill in the art having the cited references would have had a reasonable expectation of success to administer by intranasal route, the known therapeutic peptide Semax (i.e., instant SEQ ID NO:1) to an MPS III patient for the purpose of increasing BDNF in such patient to specifically provide neuroprotection to the patient to arrive at the presently claimed invention.
Thus, the claims as a whole are rendered obvious over the combination of cited references.
Conclusion
No claim is allowed.
Related art which may be applied in a future office action if appropriate:
Beard et al in “Axonal dystrophy in the brain of mice with Sanfilippo syndrome”, Exp Neurol 08/06/2017, Vol 295, pages 243-255; IDS ref). Beard et al teach a patient suffering from a neurodegenerative lysosomal storage disorders including Mucopolysaccharidosis type IIIA which is also called MPS IIIA or Sanfilippo syndrome. (See Abstract; pg. 243, left col, first para.) Beard et al disclose that MPS IIIA results in degenerative changes including progressive accumulation of ubiquitin-positive lesions/axonal dystrophy.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
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