DETAILED ACTION
Claim Status
As of the Non-Final Office Action mailed 4/21/2026, claims 1-12 were pending.
In Applicant's Response filed on 7/21/2026, claim 12 was amended, claims 1-11 were canceled, and claims 13-21 are newly added.
As such, claims 12-21 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 1-11 under 35 U.S.C. 112(a) for lack of enablement is moot in view of the cancelation of these claims.
The rejection of claim 11 under 35 U.S.C. 101 for being directed to non-statutory subject matter is moot in view of its cancelation.
The rejection of claims 1-10 under 35 U.S.C. 101 for being directed to a product of nature is moot in view of its cancelation.
The rejection of record of claims 1-2 and 5-11 under 35 USC § 102(a)(1) as being anticipated by Rodrigues et al (Stem Cell Rev and Rep 10, 13 Nov 2013) is moot in view of its cancelation.
The rejection of record of claims 1-12 under 35 USC § 102(a)(1) and (a)(2) as being anticipated by Goldman et al (US 10,279,051 B2, 2/10/2017; published 5/7/2019) is moot in view of its cancelation.
Claim Objections
Claims 18-19 are objected to because of the following informalities:
Claim 18 contains improper spacing between the chemical names of the PKC-β inhibitors.
Claim 19 contains improper spacing between the names of the BMP inhibitors claimed in the Markush groups.
Appropriate correction is required.
Claim 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.
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.
Claim 14 and 19 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.
Claim 14 recites, inter alia, “wherein the degenerative brain disease is a disease selected from . . . mild cognitive impairment.” Mild cognitive impairment is not a degenerative brain disease (i.e., progressive passive breakdown of tissue and leading to worsening neurological function over time). There is no nexus between the scope of degenerative brain diseases embraced by the claim and this specific syndrome as claimed. The examiner notes that mild cognitive impairment embraces a range of conditions such as drug/alcohol impairment, stroke, etc. Thus, the claim is indefinite.
Claim 19 contains “6-[4-[2-(1-piperinyl)ethoxy]phenyl]-3-(4-pyridinyl)-pyrazolo [1,5-a]pyrimidine)”, “4-[6-[4-(1-nethylethoxy)phenyl]pyrazolo[1,5-a]pyrinidine-3-yl]-quinoline”, “3-[(6-amino-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenol”, and “5-(6-(4-(1-piperazinyl)phenyl)pyrazolo[1,5-a]pyrimidine-3-yl)quinolone” in parentheses. The use of the parentheses renders the claim indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention or are merely exemplary. Since the claim contains the name of the BMP inhibitors, the examiner suggests removing these.
Claim Rejections - 35 USC § 102
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 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.
Rejection 1
Claim(s) 12-15 is/are rejected under 102(a)(1) and (a)(2) as anticipated by Goldman (US 10,279,051 B2, 2/10/2017; published 5/7/2019; of record). Please note that this rejection has been modified to include newly added claims 13-15.
Regarding claim 12 and 14, Goldman teaches a method of treating frontotemporal dementia, said method comprising selecting a subject having frontotemporal dementia; and administering to the selected subject a preparation of CD44+ astrocyte-biased glial progenitor cells at a dosage effective to treat the frontotemporal dementia in the subject (see claim 1 of Goldman).
Regarding claim 13, he glial progenitor cells are derived from fetal tissue, embryonic stem cells, or induced pluripotent stem cells (see claim 8 of Goldman).
Regarding claim 15, Goldman teaches that the cells can be administered via any standard route of administration known in the art, including, but not limited to, parenteral (e.g., intravenous, intraarterial, intramuscular, subcutaneous injection, intrathecal), oral (e.g., dietary), topical, transmucosal, or by inhalation (e.g., intrabronchial, intranasal or oral inhalation, intranasal drops).
Accordingly, Goldman anticipates the invention of instant claims 12-15.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive.
On p. 9 of Remarks, Applicant argues that Goldman does not disclose “neural precursor cells” as claimed. Applicant states that the NPCs as in para 10 of the instant specification are “self-renewing cells capable of differentiating into neurons, astrocytes, or oligodendrocytes. Applicant argues that the cells of Goldman are already biased toward astrocyte lineage and are different from the instantly claimed cells.
While Applicant’s arguments have been fully considered, they have not been found persuasive. "A generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus." In re Slayter, 276 F.2d 408, 411, 125 USPQ 345, 347 (CCPA 1960); In re Gosteli, 872 F.2d 1008, 10 USPQ2d 1614 (Fed. Cir. 1989) (see MPEP 2131.02). Specifically, the examiner notes that “neural progenitor cells” can include any precursor cells that can divide and differentiate into neural lineage cells. “Neural progenitor cells” as broadly claimed encompass a variety of cells, including subtypes of neural progenitor cells such as glial progenitor cells, especially since the claims do not require the cells to “retain capacity to differentiate into neurons, astrocytes, or oligodendrocytes” as argued. As per MPEP 2131.02(I), “[a] species will anticipate a claim to a genus.” As such, Applicant’s arguments are not persuasive.
Rejection 2
Claim(s) 12-15 is/are rejected under 102(a)(1) and (a)(2) as anticipated by Lee et al (WO2012068170A2, 11/15/2011; published 5/24/2012).
Regarding claim 12, Lee teaches methods for treatment of neurodegenerative diseases using neural stem cells (abstract and see claim 1 of Lee).
Regarding claim 12 and 13, Lee teaches that the stem cells are induced to differentiate into a cell with neuronal characteristics (para 28).
Lee continues to teach that the stem cell is a mammalian embryonic stem cell or a mammalian induced pluripotent stem cell (para 29).
Regarding claim 14, Lee teaches that the neurological disorder is Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, Friedreich's ataxia, Lewy body disease, spinal muscular atrophy, multiple system atrophy, dementia (see claim 56 of Lee).
Regarding claim 15, Lee teaches that the administering comprises injecting (see claim 62 of Lee).
Accordingly, Lee anticipates the invention of instant claims 12-15.
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.
Claim(s) 16-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (WO2012068170A2, 11/15/2011; published 5/24/2012) as applied to claims 12-15 above, and further in view of Hwang (WO2020091292A1, 10/23/2019; published 5/7/2020).
The teachings of Lee were recited in the above 35 U.S.C. 102 rejection as applied to claim 12 of which claims 16-21 ultimately depend. The teachings will not be repeated here.
Lee does not teach:
The neural precursor cells are differentiated by two-dimensionally culturing an embryonic body (EB) obtained by three-dimensionally culturing the pluripotent stem cells in a culture medium including a protein kinase C-β (PKC-β) inhibitor and a bone morphogenetic protein (BMP) inhibitor,
the pluripotent stem cells are obtained by culturing under feeder cell-free conditions,
the PKC-β inhibitor is selected from: 2-[1-(3-dimethylaminopropyl)-5-methoxy indol-3-yl]-3-(1H-indol-3-yl) maleimide; 3-(1-(3-imidazol-l-yl propyl)-1 H-indol-3-yl)-4-anilino-1 H-pyrrole-2,5 -dione; 3-(1 H-indol-3-yl)-4- [2-(4-methylpiperazin- 1 -yl)quinazolin-4-yl]pyrrole-2,5-dione; (3- {1-[3-(amidinothio)propyl]-1H-indol-3-yl}-3-(1-methyl-1 H-indol-3-yl)maleimide methane sulfonate; 13-hydroxyoctadecadienoic acid; bisindolylmaleimide; 2,6-diamino-N-([ 1-oxotridecyl)-2-piperidinyl]methyl)hexanamide; 4'-demethylamino-4'-hydroxystaurosporine; and 3-(13-methyl-5-oxo-6,7-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c] carbazol-12(13H)-yl)propanenitrile,
the BMP inhibitor is selected from: dorsomorphin, dorsornorphin hornolog 1 (DMH1); K02288, LDN 212854, and Noggin polypeptide,
the three-dimensionally culturing is performed for 1 day to 10 days, and
the two-dimensionally culturing is performed for 1 day to 15 days.
Regarding i)-vi), Hwang teaches differentiating stem cells into neural progenitor cells (NPCs), including protein kinase C (PKC) inhibitors and bone morphogenetic protein (BMP) inhibitors (claim 1 of Hwang).
Regarding claim 18, Hwang teaches that the PKC inhibitor can be selected from 2- [1- (3-dimethylaminopropyl) -5-methoxyindol-3-yl] -3- (1H-indol-3-yl) maleimide (2- [1- (3- Dimethylaminopropyl) -5-methoxy indol-3-yl] -3- (1H-indol-3-yl) maleimide); 3- [1- (3-imidazol-1-yl propyl-1H-indol-3-yl) -4-anilino-1H-pyrrole-2,5-dione (3- (1- (3-Imidazol- 1-yl propyl) -1H-indol-3-yl) -4-anilino-1H-pyrrole-2,5-dione); 3- (1H-indol-3-yl) -4- [2- (4-methylpiperazin-1-yl) quinazolin-4-yl] pyrrole-2,5-dione ((3- (1H-indol -3-yl) -4- [2- (4-methylpiperazin-1-yl) quinazolin-4-yl] pyrrole-2,5-dione); 3- {1- [3- (amidinothio) propyl] -1H-indol-3-yl} -3- (1-methyl-1H-indol-3-yl) maleimide methane sulfonate ((3- {1- [3- (amidinothio) propyl] -1H-indol- 3-yl} -3- (1-methyl-1H-indol-3-yl) maleimide methane sulfonate); 13-hydroxyoctadecadienoic acid; bisindolylmaleimide; 2 , 6-Diamino-N-([1-oxotridecyl) -2-piperidinyl] methyl) hexanamide (2,6-Diamino-N-([1-oxotridecyl) -2-piperidinyl] methyl) hexanamide ); 4'-dimethylamino-4'-hydroxystaurosporine (4'-demethylamino-4'-hydroxystaurosporine); And 3- (13-methyl-5-oxo-6,7-dihydro-5H-indolo [2,3-a] pyrrolo [3,4-c] carbazole-12 (13H) -yl propanenitrile (3- (13-methyl-5-oxo-6,7-dihydro-5H-indolo [2,3-a] pyrrolo [3,4-c] carbazol-12 (13H) -yl) propanenitrile) (see claims of Hwang).
Regarding claim 19, Hwang teaches that the BMP inhibitor is selected from the group consisting of Dorsomorphin, Dorsomorphin homolog 1, K 02288, LDN 212854, and Noggin polypeptides (see claims of Hwang).
Regarding claim 20-21, Hwang teaches that the suspension culture (i.e., three-dimensional culture) is cultured for 1 to 10 days and the adherent culture (i.e., two dimensional culture) is cultured for 1 to 15 days (see claims of Hwang).
Regarding claim 17, Hwang is silent to the presence of feeder cells in the culture. Thus, absent evidence to the contrary, the culture conditions described by Hwang are feeder-free.
The neural progenitor cells may be used for treatment of diseases of the central nervous system. The central nervous system diseases are, for example, stroke, dementia, Parkinson's disease, Huntington's disease, and multiple sclerosis. The central nervous system disease may be a spinal cord injury due to an injury.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to administer neural progenitor cells derived from pluripotent stem cells to treat neurodegenerative diseases as taught by Lee, where the pluripotent stem cells are cultured in PKC inhibitor and BMP inhibitor to produce the neural progenitor cells as taught by Hwang, to arrive at the instantly claimed invention. Hwang shows PKC inhibitor and BMP inhibitor can successfully be used to produce neural progenitor cells. One of ordinary skill would have been motivated to modify the method of Lee to include pluripotent stem cell culture containing PKC inhibitor and BMP inhibitor as taught by Hwang with a reasonable expectation of advantageously maintaining the ability to producing neural progenitor cells capable of being used to treat diseases of the nervous system as taught by the prior art.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Hwang et al (KR20190049178A, 11/1/2017; published 5/9/2019), which describes differentiating stem cells into neural crest stem cells using PKC inhibitor and dorsomorphin.
Neely et al (ACS Chem Neurosci. 2012 Jun 20;3(6):482-91), which describes DMH1 as a highly selective BMP inhibitor to promote neurogenesis of hiPSCs.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN C REGLAS whose telephone number is (571)270-0320. The examiner can normally be reached M-F 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras Jr can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.R./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
