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 .
Claims 1-9, 13, 14 and 17-25 are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-9 and New Claims 21-25) in the reply filed on 06/11/2026 is acknowledged. Claims 13, 14 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/11/2026.
Claims 1-9 and 21-25 were examined on their merits.
Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other form of browser-executable code at Pg. 56, Paragraph [0095] and Pg. 87, Paragraph [0151] and Pg. 88, Paragraph [0153] and Pg. 90, Paragraph [0155] and Pg. 94, Paragraph 0167] and Pg. 95, Paragraph [0172] and Pg. 96, Paragraph [0174] Applicant is required to delete the embedded hyperlinks and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms CULTURESURE™, ONESHOT™, NANOSIGHT™, SIMPLIAMP™, STEPONEPLUS™, EASY-SPRAY™, NEXTSEQ™, GENEGLOBE™, GLUTAMAX™, STERICUP™ and ZETAVIEW™ which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 5 is objected to because of the following informalities: The words “small molecule” should be inserted between “the” and “inhibitor” . Appropriate correction is required.
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.
Claim 23 is rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of producing highly proliferating cells, comprising preparing normal human astrocytes, culturing for 28 days and then contacting the normal human astrocytes with ROCK inhibitor Y (Y-27632) and TGF-β inhibitor A (A-83-01) and culturing for 14 days with one passage (see published Specification at Pg. 13, Paragraph [0208] and Pg. 15, Paragraph [0230]),
wherein the cells have an NG2 expression level higher than control normal human astrocytes (published Specification, Tables 5-6), does not reasonably provide enablement for a method of producing highly proliferating cells, comprising preparing any ectodermal cells, and then contacting the ectodermal cells with any small molecule signaling pathway inhibitor and culturing for any amount of time, wherein the cells have an NG2 expression level higher than control ectodermal cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art,
(7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
(1) the quantity of experimentation necessary
The ordinary artisan would be faced with an undue amount of experimentation in having to obtain/prepare all possible ectodermal cells, which include but would not be limited to: all cells of the spinal cord, nerves, brain, skin, mucosa, hair, nails, tooth enamel and exocrine glands. Then once obtained, the ordinary artisan would have to identify all possible cell signaling pathways, which include but are not limited to: Akt/PKB signaling pathway, AMPK signaling pathway, cAMP-dependent pathway, Eph/ephrin signaling pathway, Hedgehog signaling pathway, Hippo signaling pathway, Insulin signal transduction pathway, JAK-STAT signaling pathway, MAPK/ERK signaling pathway, mTOR signaling pathway, Nodal signaling pathway, Notch signaling pathway, PI3K/AKT/mTOR signaling pathway, TGF-β signaling pathway, TLR signaling pathway, VEGF signaling pathway and the Wnt signaling pathway and contact those cells with all possible signaling pathway inhibitors before testing those cells for; 1) high proliferation and 2) an NG2 expression level higher than control ectodermal cells.
(2) the amount or direction or guidance presented
While the Specification discusses “ectodermal” cells as cells of the central nervous system in an exemplary manner (see the Specification as filed at Pg. 11, Paragraph 0013] and Pg. 12, Paragraph [0015]), the disclosure is not limited to those cells. The Specification also indicates that any small-molecule pathway inhibitor can be used, exemplifying TGF-β, ROCK and GSK3 (see Specification as filed, Pg. 15, Paragraph [0021]). The disclosure however, does not guide or direct the ordinary artisan to what other non-exemplary ectodermal cells, signaling pathways thereof or signaling pathway inhibitors can be used to obtain the claimed results.
(3) the presence or absence of working examples
As discussed above, the working examples are drawn to a limited method of producing highly proliferating cells, comprising preparing normal human astrocytes, culturing for 28 days and then contacting the normal human astrocytes with ROCK inhibitor Y (Y-27632) and TGF-β inhibitor A (A-83-01) and culturing for 14 days with one passage (see published Specification at Pg. 13, Paragraph [0208] and Pg. 15, Paragraph [0230]), wherein the cells have an NG2 expression level higher than control normal human astrocytes (see published Specification, Tables 5-6).
(4) the nature of the invention and breadth of the claims
The invention would necessitate the ordinary artisan obtain/prepare all possible ectodermal cells. Then once obtained, the ordinary artisan would have to identify all possible cell signaling pathways, and contact those cells with all possible signaling pathway inhibitors before testing those cells for; 1) high proliferation and 2) an NG2 expression level higher than control ectodermal cells.
(5) the state of the prior art
Patthey et al. (2014) teaches that ectodermal cells are subject to multiple signaling pathways during development (Pg. 12, Fig. 1). Presumably, each pathway has putative inhibitors and inhibition of each pathway will have an effect of the fate of the ectodermal cells. Qu et al. teaches that surface ectodermal (SE) cell inhibition of TGF-βR1 with three TGF-βR1 inhibitors resulted in enhanced SE differentiation (Pg. 1, Abstract and Pg. 9, Lines 3-26). The prior art however, does not recognize that any ectodermal cell pathway can be inhibited with resulting increased NG2 expression.
(7) the predictability or unpredictability of the art
The art is inherently unpredictable being based in complex biological systems. For example, each ectodermal cell type would have cell signaling pathways which may or may not be the same as another ectodermal cell and which may or may not be subject to inhibitors which may or may not inhibit that pathway. The only way to ascertain this is the testing of all possible combinations encompassed by the instant claims to determine the effect, if any, on NG2 expression.
For all of the above reasons, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
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 8 is 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 8 recites, “mature cells” and “progenitor cells”. It is unclear what cells are being referred to as “mature” or “progenitor” cells as Claim 8 depends from Claim 1 which only recites “ectodermal cells” and “highly proliferating cells”. Thus, it cannot be determined if the limitations of Claim 8 refer to the cells recited in Claim 1 or to other unrecited cells.
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, 7-9, 21, 22, 24 and 25 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Yu et al. (2012), cited in the IDS, as evidenced by Itoh et al. (2006).
Yu et al. teaches a method wherein ectodermal cells (astrocytes) are prepared from the spinal cord of neonatal rats, cultured, then contacted with a small-molecule signaling pathway inhibitor (the ROCK inhibitor Y27632 at 10 µm) and performing additional culturing in the presence of the inhibitor before isolating the cells for cell counting, wherein Y27632 contact enhanced astrocyte proliferation (e.g. increased cell number and meeting the definition in the Specification as published at Pg. 5, Paragraph [0104] of being “highly proliferating”) greater than 1x over control after 48 days of culture (Pg. 1115, Column 1, Paragraphs 2.1 and 2.2 and Pg. 1116, Fig. 1D), reading on Claims 1, 2, 3, 4, 5, 7, 24 and 25.
With regard to Claim 8, it would be expected that the cells of Yu et al. would express at least one gene specific to mature cells and progenitor cells at the same level as non-treated ectodermal cells because this is a characteristic feature of the claimed cells which are the same as the cells of the prior art.
With regard to Claims 9 and 22, it would be expected that the cultured neonatal rat astrocytes of Yu et al. would also be negative for nestin because Itoh et al. evidences that cultured rat neonatal astrocytes are negative for nestin (Pg. 1382, Column 1, 2nd paragraph and Pg. 1383, Column 2, 2nd paragraph and Pg. 1384, Fig. 1C).
With regard to Claim 21, the ectodermal cells (astrocytes) of Yu et al. would be expected to have characteristics of ectodermal cells, being as they are ectodermal cells.
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.
Claims 1-5, 6, 7, 8, 9, 21, 22, 24 and 25 are rejected under 35 U.S.C. § 103 as being unpatentable over Yu et al. (2012), cited in the IDS, as applied to Claims 1-5, 7, 8, 9, 21, 22, 24 and 25 above, and further in view of Lindholm et al. (1992) and Patel et al. (2021).
The teachings of Yu et al. were discussed above.
Yu et al. did not teach a method wherein the inhibitor comprises a TGF-β receptor inhibitor in a concentration range of 0.001-100 µm, as required by Claim 6.
Lindholm et al. teaches that TGF-β is a strong inhibitor of astrocyte proliferation (Pg. 395, Abstract).
Patel et al. teaches the treatment of cortical neurons with the small molecule TGF-β inhibitor SB431542 at 10 µm (Pg. 6, Column 1, Lines 27-29 and Pg. 5, Fig. 4).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yu et al. of enhancing astrocyte proliferation by culturing the astrocytes in the presence of the small molecule ROCK inhibitor Y27632 at 10 µm to substitute the small molecule TGF-β inhibitor SB431542 at 10 µm taught by Patel et al. because both Y27632 and SB431542 are both known in the art as small molecule inhibitors, and in view of Lindholm, inhibition of TGF-β, would also be expected to increase astrocyte proliferation, similar to ROCK inhibition. Those of ordinary skill in the art would have been motivated to make this substitution based on the availability of compounds and artisan preference for a small molecule inhibitor to stimulate astrocyte proliferation. There would have been a reasonable expectation of success in making this modification because both ROCK inhibition and TGF-β inhibition would be expected to increase astrocyte proliferation and small molecule ROCK and TGF-β inhibitors are known in the art.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 07/02/2026
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