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 .
This action is in response to the papers filed August 04, 2026.
Claims 1-41 are pending in the application as per claims filed on 06/07/2024.
Applicant's election with traverse of Claims 1-17 and 30-41 in the reply filed on August 04, 2026 is acknowledged.
The traversal is on the ground(s) that claims 18 and 30 comprise overlapping subject matter and therefore the claims should be rejoined. Moreover, Applicant states that there are only categorical grounds explained for serious search burden and not specific explanation of the grounds.
This is not found persuasive because the basis of the restriction is the groups of invention are distinct. The scopes of the invention do not necessarily overlap as claim 18’s steps are not necessarily the steps within claim 30. Claim 18 comprises culturing to form an explant of any tissue, healthy or not, and selecting specifically for c-kit positive cells and isolating those cells. Claim 30 comprises a step of extracting neural stem cells from healthy neural tissue which is then cultured and expanded, the cells are c-kit positive and then administering a dose of the cultured and expanded cells to an area of tissue repair. Regarding search burden, methods of isolation and cell culture are not necessarily in the same field of search as methods of treatment for specific disease and disorders additionally, as mentioned before, they have different classification categories which would need to be searched.
Claims 18-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. The examiner appreciates Applicants’ correction in relation to inadvertently unassigned claim 19-29 in the restriction requirement filed on 06/04/2026. Applicant timely traversed the restriction (election) requirement in the reply filed on August 04, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 1-17 and 30-41 are examined on the merits. Claims 1 and 30 are independent claims.
Priority
The present application is a DIV of US Application 16/083,011 (ABN) filed September 07, 2018.
Thus, the earliest possible priority for the instant application is September 07, 2018.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-17 and 30-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1 and 30 recite a method of treating or preventing a neurological disease or disorder, or repairing and/or regenerating damaged neural tissue, in a subject in need thereof comprising administering isolated neural stem cells expressing c-kit.
The breadth of the claims are extremely broad encompassing any dosage, any neurological disease, any route of administration at any site, any amount of time interval before or after the onset of symptoms or diagnosis.
The specification provides no working examples of the claimed invention where cells are administered. Instead, the invention is directed towards harvesting and culturing mouse NSCs (para. 0256, Example 1 and Example 2).
The only mention of treatment is that in certain embodiments the composition comprising the NSCs can be formulated for catheter or direct injection (para, 0054) or in an embodiment saying that it is a method of treatment or prevention of neurodegenerative disease such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Batten disease and/or ataxia telangiectasia (para. 019).
In the current state of the art, there is no means of preventing any and all neurological diseases and disorders. NSCs are known in the art to prevent the further progression of the disease and treat symptoms, but not disease prevention. Even known NSC therapies have a level of unpredictability without further guidance.
Frawley (Biomedicines, 2025, 13(1), 35) teaches many challenges to apply NSCs to therapies for neurodegenerative disorders such as ALS. “Common delivery procedures such as intraspinal injections and transplantation are technically demanding and raise concerns about patient safety, long-term efficacy, and the moral implications of using fetal tissue. These issues are further complicated by the fact that fetal-derived tissues are limited in availability, making large-scale or routine clinical applications unfeasible. Furthermore, the genetic modification of fetal or embryonic NSCs, which might be necessary to enhance their therapeutic potential, is often seen as non-compliant with ethical standards due to fears of unintended genetic consequences and potential misuse. Adult-derived NSCs can circumvent many of these ethical concerns and allow for personalized therapies that reduce risks of immune rejection and align more closely with regulatory and societal expectations. Multiple animal model trials [Table 2] have used SOD1G93A rodents as the main subjects to model disease progression and efficacy of human NSCs (hNSCs) with ALS [61]. These trials indicate a beneficial effect of intraspinal hNSC injection primarily in L1–L4 in pre/early symptomatic animal models. However, they face comparison issues related to the genetic background variability in mix-strained mice colonies and encounter mixed results concerning hNSC migration in surrounding tissue.” (Table 4).
Therefore, an undue burden for experimentation is placed on the artisan to be able to utilize NSCs expressing c-kit to treat or prevent any neurological disorder or disease in any subject by any means.
Claim Rejections - 35 USC § 112
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.
Claims 5, 8-9, 12, 13, 15-17, 25, 28, 29, and 30-41 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.
Regarding claims 12, 13, 15-17, 25, 28, 29, 30, 36, 37, and 38 recite “and/or.” It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only one option, or all options, or, “or” would imply that the options are in the alternative. For example, Claim 12 recites and/or in regard to growth factors in a culture of NSCs, which could mean only one growth factor, all growth factors, or particular growth factors in the alternative.
Claims dependent on independent claim 30 are additionally rejected for being indefinite.
Claim 5 is indefinite in its recitation of “lineage-negative cells” . The term“lineage-negative cells” is not defined by the claim, the specification does not provide a definition, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention as the phrase not does it have a universally accepted meaning in the context of neural stem cells.. Appropriate action is required. Claim 8 is indefinite in its recitation of “lineage-positive cells” . The term “lineage-positive cells” is not defined by the claim, the specification does not provide a definition, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention as the phrase not does it have a universally accepted meaning in the context of neural stem cells.. Appropriate action is required. Claim 9 is rejected as dependent on claim 8.
Appropriate correction is required.
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.
Claims 1, 5, 8-11 and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bantubungi (Mol. Cell. Neurosci. 37 (2008) 454–470).
Regarding claim 1, Bantubungi teaches a method of transplantation to treat neurological disease and disorders in rat models with striatal lesions comprising administering rat neural stem cells from rat embryos neural tissue which express c-kit (p. 456, 1st column; Fig 5A; p. 459, 1st column).
Regarding claim 5, Bantubungi teaches that almost all of the cells obtained coexpress GFAP and nestin (Fig 1.) Therefore, it is interpreted that the composition comprising neural stem cells is heterogenous and has lineage negative cells.
Regarding claims 8-9, Bantubungi teaches the cells express GFAP (i.e. lineage-positive cells) (Fig. 1; p. 456, 1st column).
Regarding claim 10-11, Bantubungi teaches neural stem cells are expanded in culture prior to administration to the subject in the presence of EGF (i.e. growth factors) (p. 465, 2nd column).
Regarding claim 14-15, Bantubungi teaches administering the neural stem cells are injected directly to the tissue at the site of the brain lesion (p. 466, 1st column).
Regarding claim 16-17, Bantubungi teaches the rat models with lesions model Huntington’s Disease (i.e. neurodegenerative disease) (Abstract, Title).
Therefore, Bantubungi anticipates the invention.
Claim Rejections - 35 USC § 103
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.
Claims 1-4, 6-7, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Bantubungi (Mol. Cell. Neurosci. 37 (2008) 454–470) in view of Guo (nature protocols VOL.7 NO.11 (2012) 2005-2009)
As discussed in the above 102 rejection, regarding claim 1, Bantubungi teaches a method of transplantation to treat neurological disease and disorders in rat models with striatal lesions comprising administering rat neural stem cells from rat embryos neural tissue which express c-kit (p. 456, 1st column; Fig 5A; p. 459, 1st column).
However, regarding claim 2, the neural stem cells are adult neural stem cells.
Guo teaches that adult neural stem cells can be isolated from an adult tissue from the brain’s dentate gyrus (DG) and subventricular zone (SVZ) (Abstract; Figure 1; p. 2011, para 3).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to isolate the NSCs of Bantubungi from adult tissues such as the dentate gyrus and SVZ as taught by Guo in addition to the embryos NSCs which express c-kit in order to obtain adult neural stem cells with a reasonable expectation of success. An artisan would have been motivated to do so as Guo teaches that NSCs are readily isolated from those regions.
Regarding claim 3, Bantubungi and Guo make obvious claim 1. Moreover, Guo teaches the neural stem cells are from the dentate gyrus of the neural tissue specimen (p. 2006).
Regarding claim 4, Bantubungi and Guo make obvious claim 1. Moreover, Guo teaches the neural stem cells are from the subventricular zone of the neural tissue specimen (p. 2006).
Regarding claims 6-7, Bantubungi and Guo make obvious claim 1. Moreover, Guo teaches Sox2 expression within the composition of cultured NSCs (p. 2011, para 2). Therefore, Guo teaches the NSCs comprise progenitor cells.
Regarding claim 12, Bantubungi and Guo make obvious claim 1. Moreover, Guo teaches NSCs are cultured with FGF-2 (bFGF) (p. 2011, para 4).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 13 and 30-41 are rejected under 35 U.S.C. 103 as being unpatentable over Bantubungi (Mol. Cell. Neurosci. 37 (2008) 454–470) in view of Guo (nature protocols VOL.7 NO.11 (2012) 2005-2009) as applied to claim 1 above and in further view of Westerlund (Neurosurgery 57(4):p 779-784, October 2005).
As discussed in the above 103 rejection and incorporated herein in its entirety, Bantubungi teaches a method of transplantation to treat neurological disease and disorders in rat models with striatal lesions comprising administering rat neural stem cells from rat embryos neural tissue which express c-kit and Guo provides teachings on isolating NSCs from SVZ and DG.
However, regarding claim 13 and 40, the neural tissue specimen is obtained from the subject (is autologous).
Westerlund teaches that locations such as the SVZ and ventricular wall can be sources of NSCs for autologous transplant through endoscopic biopsy (Abstract, p. 6). Autologous sources have been proposed due to ethical, political and practical considerations (p. 6, 1st column).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to harvest the tissue from the subject in order to produce autologous NSCs instead of the NSCs of Bantubungi and Guo for transplantation as taught by Westerlund with a reasonable expectation of success. An artisan would have been motivated to do so as autologous sources have been proposed due to ethical, political and practical considerations (p. 6, 1st column).
Regarding independent claim 30, the combination of Guo, Bantubungi and Westerlund teach repairing lesions (i.e. repairing tissue) through administering NSCs which are derived from the patient through harvesting tissue from the subject. These NSCs are c-kit positive when expanded and cultured with a reasonable expectation of success. As there is no dosage determined for the effective dosage, it is determined that the combination of references meet these parameters. Note that Westerlund renders obvious the use of neural tissue specimen that is obtained from the subject (is autologous) (claims 13 and 40).
Regarding claim 31, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Guo teaches the neural stem cells are from the dentate gyrus of the neural tissue specimen (p. 2006).
Regarding claim 32, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Guo teaches the neural stem cells are from the subventricular zone of the neural tissue specimen (p. 2006).
Regarding claims 33-34, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Guo teaches Sox2 expression within the composition of cultured NSCs (p. 2011, para 2). Therefore, Guo teaches the NSCs comprise progenitor cells.
Regarding claims 35-36, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Bantubungi teaches the NSCs express GFAP (i.e. lineage-positive cells) (Fig. 1; p. 456, 1st column).
Regarding claim 37-38, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Guo teaches NSCs are cultured with FGF-2 (bFGF) (p. 2011, para 4) and Bantubungi teaches neural stem cells are expanded in culture prior to administration to the subject (p. 456, 2nd column).
Regarding claim 39, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Moreover, Bantubungi teaches administering the neural stem cells are injected directly to the tissue at the site of the brain lesion (p. 466, 1st column).
Regarding claim 41, Regarding claim 39, Bantubungi, Guo and Westerlund make obvious claim 30. Moreover, Bantubungi teaches allogenic transplantation to lesions (abstract, Fig 5A; p. 459, 1st column)
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Conclusion
No claims are allowed.
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/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
