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 OFFICE ACTION
This Office Action is in response to the papers filed on 10 September 2025. In light of the 13 June 2015 priority date, a second Non-Final Office Action is set forth below.
CLAIMS UNDER EXAMINATION
Claims 42-49 are pending and have been examined on their merits.
PRIORITY
The Applicant claims priority to Provisional Application 62/175239, filed on 13 June 2015. The disclosure states mice are treated with one drop (6µl) of ACCS intranasally ([0133]). The disclosure states one dose, or 2, 3, 4 or more doses can be administered ([0094]). Therefore the Provisional Application provides support for at least 6µl.
WITHDRAWN REJECTIONS
The previous rejections are with withdrawn.
NEW REJECTIONS
New rejections have been made in light of the 13 June 2015 priority date.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 42-49 are rejected under 35 U.S.C. 103 as being unpatentable over Sing et al. (previously cited; Methods For Treating Nervous System Injury And Disease. Patent 8197804 2012) in view of Frey (Methods, Pharmaceutical Compositions and Articles of Manufacture for Administering Therapeutic Cells to the Animal Central Nervous System (US2009/0068155) as evidenced by National Organization of Rare Diseases (previously cited, Neuromyelitis Optica Spectrum Disorder. Pages 1-20, 2018).
Sing et al. teach a method of treating nervous system injury and degenerative disease (Column 4, line 65 through line 2 of column 5). Sing teaches treating a human (column 11, line 19). The compositions and methods can be used to treat neuromyelitis optica (column 18, line 3). Neuromyelitis Optica (Devic's Disease) is an inflammatory disease of the CNS in which there are episodes of inflammation and damage to the myelin that almost exclusively affect the optic nerves and spinal cord (column 17, lines 60-64). Therefore Sing treats an optic nerve disorder.
Sing administers a composition comprising conditioned medium from amnion derived multipotent progenitor cells, referred to as “amnion-derived cellular cytokine solution” or “ACCS” (column 5, lines 8-12). Sing teaches cells are removed from the conditioned medium (column 9, line 11).
Regarding the components of the ACCS:
Sing teaches the TSE cells secrete VEGF, angiogenin, PDGF, TGFβ2, at least one of TIMP-1 and TIMP-2, wherein each secreted factor is secreted physiologically relevant levels in a physiologically relevant temporal manner into the extracellular space or into surrounding culture media (column 7, lines 55-65). Sing teaches each of the factors recited in claim 42, and states each is secreted at physiological levels. Therefore the secreted levels would read on the claimed physiologic concentrations.
Sing discloses the following method of generating conditioned medium:
Example 2 Generation of ACCS
The AMP cells of the invention can be used to generate ACCS. The AMP cells were isolated as described herein and 1×106 cells/mL were seeded into T75 flasks containing 10 ml culture medium. The cells were cultured until confluent, the medium was changed and ACCS was collected 3 days post-confluence. Skilled artisans will recognize that other embodiments for collecting ACCS from confluent cultures, such as using other tissue culture vessels, including but not limited to cell factories, flasks, hollow fibers, or suspension culture apparatus, are also contemplated by the methods of the invention (see above). It is also contemplated by the instant invention that the ACCS be cryopreserved following collection. It is also contemplated that the ACCS be lyophilized or formulated for sustained-release.
The art teaches the use of culture medium comprising human albumin and 10 ng/ml EGF (column 19, line 34, lines 54-55).
Examiner notes the following from the Instant Specification (Example 2):
Example 2: Generation of ST266
The AMP cells of the invention were used to generate ST266 as follows. A placenta was obtained and the amnion was isolated from the placenta, amnion epithelial cells were enzymatically released from the amnion, the released amnion-derived epithelial cells were collected, the collect cells were cultured in IMDM culture medium that was supplemented with 0.5% human serum albumin and 10 ng/mL recombinant human EGF. The culture medium was collected after about 2-3 days and fresh culture medium was applied. The collected of culture medium and application of fresh culture medium was repeated a plurality of times. It is contemplated by the instant invention that the ST266 be cryopreserved, lyophilized, irradiated, diluted, concentrated or formulated for sustained-release following collection.
Because Sing and the Instant Invention both collect conditioned medium from the same type of cells after 3 days of culture in a medium containing EGF and albumin, the conditioned medium of Sing would be expected to inherently have the same secreted cellular factors.
Regarding the dose and administration:
Singh teaches administering 50 µl of conditioned medium (Example 4).
Sing teaches delivery to a “target site” (column 22, line 55) and delivery to a “desired location” (column 22, line 60).
The deficiency of Sing is the disclosure does not teach a device capable of intranasal administration as recited in claim 42.
Frey teaches a method of treating the central nervous system by intranasal application a therapeutic composition to the upper-third of the nasal cavity, thereby bypassing the blood-brain barrier (Abstract; [0003]). Bypassing the blood-brain barrier avoids unwanted systemic exposure as well as invasive delivery methods ([0022]). The composition comprises at least one therapeutic cell and regulatory factors (Abstract) including trophic, growth factors and cytokines ([0015] [0016] [0068] [0070]).
Frey teaches intranasal administration of at least one regulatory agent to the upper third of the nasal cavity, alone and/or in combination with the therapeutic cells (multipotent stem cells [0034]), will regulate development of the therapeutic cell transported to the CNS ([0075]). Therefore Frey teaches regulatory agents can be administered alone.
The composition is dispensed and applied intranasally to the upper third of the nasal cavity as a powdered or liquid nasal spray ([0119]). Instant specification teaches the disclosed targeted administration is performed using a liquid nasal spray ([0008]).
Frey teaches intranasal administration using a liquid nasal spray. Therefore Frey teaches a device capable of targeted intranasal administration.
Frey teaches the following ([0049] [0050]):
Therapeutic cells and/or pharmaceutical compositions thereof may be administered to the olfactory nerve, for example, through the olfactory epithelium located at the upper third of the nasal cavity. Such administration can employ extracellular or intracellular (e.g., transneuronal) anterograde and retrograde transport of the regulatory agent entering through the olfactory nerves to the brain and its meninges, to the brain stem, or to the spinal cord. Once the therapeutic cells and/or pharmaceutical composition thereof is dispensed into or onto tissue innervated by the olfactory nerve, the therapeutic cells and/or pharmaceutical composition and/or components thereof may be transported through the tissue and travel along olfactory neurons into areas of the CNS including the brain stem, cerebellum, spinal cord, cerebrospinal fluid, olfactory bulb, and cortical and subcortical structures.
The blood-brain barrier is bypassed in the present invention by application of the therapeutic cells and/or pharmaceutical composition(s) comprising therapeutic cells by application to the upper third of the nasal cavity. The therapeutic cells and/or pharmaceutical composition of the invention migrate from the nasal mucosa through foramina in the cribriform plate along the olfactory neural pathway and into the CNS.
It would have been obvious to deliver Sing’s ACCS by targeted intranasal administration. Sing administers a composition comprising cytokines and growth factors and Frey teaches these components can be administered by application to the upper third of the nasal cavity. One would have been motivated to administer ACCS using Frey’s delivery method to avoid unwanted systemic exposure and invasive administration. One would have had a reasonable expectation of success since Frey teaches intranasal administration can deliver regulatory factors. One would have expected similar results since both references are directed to methods of delivering regulatory factors to treat nervous system disorders. Therefore claim 42 is rendered obvious.
It would have been obvious to administer ST66 in combination with another agent since Sing teaches both AMP (hence, the cells) and ACCS may be administered (column 1, lines 20-25). Because Sing teaches both compositions treat neurological disorders, one of ordinary skill would administer both therapeutics to have an enhanced effect. See In re Kerkoven (205 USPQ 1069). Therefore claim 43 is included in this rejection.
Because Sing teaches AMP cells can also be administered to treat disorders, they are interpreted to be “active”. Therefore claim 44 is included in this rejection.
As set forth above, the conditioned medium taught is prepared using the same cells disclosed in the Instant Specification. Therefore the conditioned medium taught by Singh is interpreted to inherently have the same properties as the composition recited in claim 45. Therefore claim 45 is included in this rejection. Claim 46 is rejected on the same grounds.
Sing administers 50 ul of ACCS (supra). Claim 47 is rendered obvious.
Regarding claim 48:
Sing treats neuromyelitis optica (supra). As evidenced by the National Organization of Rare Diseases (NORD), Neuromyelitis optica (NMOSD), also known as Devic disease, is “a chronic disorder of the brain and spinal cord dominated by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis)” (See page 1, first paragraph). Therefore Sing treats optic neuritis.
Claim 48 Examiner notes the claim is not directed to treating multiple sclerosis. Examiner notes Sing also teaches the disease treated may be “Multiple Sclerosis” (column 6, lines 9-10). The claim does not distinguish the optic neuritis taught by Sing from optic neuritis caused by multiple sclerosis. Therefore claim 48 is rendered obvious.
Sing treats optic neuritis (supra). Therefore claim 49 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 42-49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13 and 18 of Steed et al. (Methods For Preventing Or Treating Optic Neuritis US2017/0202919 in view of Sing et al. This is a provisional nonstatutory double patenting rejection.
Claim 13 of the ‘919 Application is directed a method for preventing or treating optic neuritis (hence, an optic nerve disorder) in a patient in need thereof comprising intranasally administering to the patient a therapeutically effective amount of (Amnion-derived Cellular Cytokine Solution (ACCS). As evidenced by the specification, ACCS comprises the cellular factors recited in instant claim 42 (see ([0032] [0039] [0040] of PG Pub). Claim 18 recites the intranasal administration comprises the steps of a) delivering the ACCS or AMP cells onto the nasal mucosa adjacent to the foramina of the cribriform plate located at the superior aspect of the nasal cavity, and b) allowing the ACCS or AMP cells to permeate through the foramina into the cranial cavity at the location of the optic nerve.
The teachings of Sing as set forth above are reiterated. Sing treats a human Sing et al. teach a therapeutic dose of 50 µL. Singh teaches administering 50 µl of conditioned medium . (Example 4). It would have been obvious to administer at least 6 µl. One would have been motivated to do so since Sing teaches 50 µl of conditioned medium can be administered to treat an optic nerve disorder. One would have expected similar results since Steed and Sing both administer the same composition to treat optic nerve disorders. Claim 42 is rendered obvious.
Regarding claim 43: It would have been obvious to administer ST66 in combination with another agent since Sing teaches both AMP (hence, the cells) and ACCS may be administered (column 1, lines 20-25). Because Sing teaches both compositions treat neurological disorders, one of ordinary skill would administer both therapeutics to have an enhanced effect.
Regarding claim 44: Because Sing teaches AMP cells can also be administered to treat disorders, they are interpreted to be “active”.
Regarding claims 45-46: As set forth above, the conditioned medium taught is prepared using the same cells disclosed in the Instant Specification. Therefore the conditioned medium taught by Singh is interpreted to inherently have the same properties as the composition recited in claim 45.
Steed teaches optic neuritis (supra). This reads on instant claims 48-49.
APPLICANT’S ARGUMENTS
The Arguments made in the response filed on 10 September 2025 are acknowledged. Argument 1: The arguments state that because the specification discloses a dose of 6 µl, all doses above 6 µl are supported.
Response to argument 1: New grounds of rejection have been made above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653