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 1-23 are pending and under examination in the instant application.
Priority
The instant application, filed 03/15/2024 is a national stage entry under 35 USC 371 of
PCT/EP2022/076103 (filed 09/20/2022). Also, acknowledgment is made of applicant’s claim for foreign priority
under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP21197737.6, filed
on 09/20/2021. Therefore, the earliest possible priority for the instant Application is 09/20/2021.
Claim Objections
Claims 4-5, 9, 11-15 and 19-23 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only and cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). In this case, claims 4-5, 11-15 recite “in vitro cell culture according to any one of claims…” and claims 19-23 recite “The method according to any one of claims…”. Accordingly, the claims 4-5, 11-15 and 19-23 have not been further treated on the merits.
Also, claim 9 recites “The in vitro cell culture according to claim 1 or 9”. A claim cannot depend on itself.
Appropriate correction of the claims is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 15 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory
subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter
because “use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to
comply with 35 U.S.C. 101.
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 9 and 15 are is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 claim 9, it recites “The in vitro cell culture according to claim 1 or 9”. This recitation introduces ambiguity and renders the claim indefinite since a claim cannot depend on itself and there is no way of knowing what in vitro cell culture is actually being claimed. In view of the substantial issues of indefiniteness because the claim does not set forth a complete claimed product, the metes and bounds of this claim cannot be determined.
Regarding claim 15, it recites “Use of the in vitro cell culture..”. It is a “use” claim. The meets and bound of the claims are indefinite wherein the conjugate is claimed “for use”. MPEP 2173.05(q) states attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness. Recitation of a use without any active, positive steps delimiting how this use is actually practiced is indefinite.
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.
(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.
Claim(s) 1-3, 6-10 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Wicks et al. (WO2018027112, filed 08/04/2017, and published on 02/08/2014), as evidenced by Fernandopulle et al. (Fernandopulle et al., “Transcription Factor-Mediated Differentiation of Human iPSCs into Neurons”. Curr Protoc Cell Biol. 2018 Jun;79(1):e51. doi: 10.1002/cpcb.51. Epub 2018 May 18.), Neyrinck et al. (Neyrinck et al., “SOX9-induced Generation of Functional Astrocytes Supporting Neuronal Maturation in an All-human System”. Stem Cell Rev and Rep 17, 1855–1873 (2021)), and García-León et al. (García-León et al., “SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells”. Stem Cell Reports. 2018 Feb 13;10(2):655-672).
Regarding claim 1, Wicks et al. teaches an in vitro cell culture comprising neuronal cells derived from iPSC, astrocytes derived from iPSC, and oligodendrocytes derived from iPSC (Abstract, claim 1, page 2, lines 9-15, and page 6, lines 24-29).
Wicks et al. does not specifically mention that neuronal cells are derived from iPSC with an NGN2 transgene; however, Fernandopulle et al. provides evidence that rapid and robust differentiation of cortical neurons from hiPSCs is done via induced expression of the neurogenin-2 (NGN2) transcription factor (page 26, section BASIC PROTOCOL 5: DIFFERENTIATION OF i3NEURONS). Therefore, transfecting iPSCs specifically with an NGN2 transgene to generate iPSC-derived neuronal cells is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Also, Wicks et al. does not specifically mention that astrocytes are derived from iPSC with an SOX9 transgene; however, Neyrinck et al. provides evidence that functionally mature human astrocytes can be generated by SOX9 overexpression for 6 days in pluripotent stem cell (PSC)-derived neural progenitor cells (Abstract). Therefore, transfecting iPSCs specifically with an SOX9 transgene to generate iPSC-derived astrocytes is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Moreover, Wicks et al. does not specifically mention that oligodendrocytes are derived from iPSC with a SOX10 transgene; however, García-León et al. provides evidence that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive oligodendrocytes (Ols) from hPSCs in only 22 days (Abstract). Therefore, transfecting iPSCs specifically with an SOX10 transgene to generate iPSC-derived oligodendrocytes is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Regarding claim 2: Following discussion of claim 1 above, although Wicks et al. does not specifically mention that neuronal cells are derived from iPSC with an NGN2 transgene, Fernandopulle et al. provides evidence that rapid and robust differentiation of cortical neurons from hiPSCs is done via induced expression of the neurogenin-2 (NGN2) transcription factor (page 26, section BASIC PROTOCOL 5: DIFFERENTIATION OF i3NEURONS). Therefore, transfecting iPSCs specifically with an NGN2 transgene to generate iPSC-derived neuronal cells is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Regarding claim 3: Following discussion of claim 1 above, although Wicks et al. does not specifically mention that neuronal cells express NGN2, Fernandopulle et al. provides evidence that neuronal cells express NGN2 (page 43, paragraph 1). Therefore, expressing NGN2 by neuronal cells is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Regarding claims 6-7: Following discussion of claim 1 above, although Wicks et al. does not specifically mention that astrocytes express SOX9, Neyrinck et al. provides evidence that astrocytes express SOX9 (page 1861, column 2, Results). Therefore, expressing SOX9 by the astrocytes is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Regarding claims 8, 9, and 10: Following discussion of claim 1 above, although Wicks et al. does not specifically mention that oligodendrocytes express SOX10, García-León et al. provides evidence that oligodendrocytes express SOX10 (page 657, column 1, Results). Therefore, expressing SOX10 by the oligodendrocytes is inherently and necessarily present in Wicks et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
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.
Claim(s) 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wicks et al. (WO2018027112, filed 08/04/2017, and published on 02/08/2014), in view of Fernandopulle et al. (Fernandopulle et al., “Transcription Factor-Mediated Differentiation of Human iPSCs into Neurons”. Curr Protoc Cell Biol. 2018 Jun;79(1):e51. doi: 10.1002/cpcb.51. Epub 2018 May 18.), Neyrinck et al. (Neyrinck et al., “SOX9-induced Generation of Functional Astrocytes Supporting Neuronal Maturation in an All-human System”. Stem Cell Rev and Rep 17, 1855–1873 (2021)), and García-León et al. (García-León et al., “SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells”. Stem Cell Reports. 2018 Feb 13;10(2):655-672).
Regarding claim 16, Wicks et al. teaches a method of preparing an in vitro culture of iPSC derived neuronal cells, iPSC derived astrocytes and iPSC derived oligodendrocytes comprising adding endothelial cells, and optionally pericytes, to an organoid containing one or more of astrocytes, microglia, oligodendrocytes and neurons. (claims 17-18).
However, Wicks et al. fails to teach inducing iPSC, transfected with an inducible NGN2 transgene, into neuronal cells, inducing iPSC, transfected with an inducible SOX9 transgene, into astrocytes, inducing iPSC, transfected with an inducible SOX10 transgene, into oligodendrocytes.
However, Fernandopulle et al. teaches that rapid and robust differentiation of cortical neurons from hiPSCs is done via induced expression of the neurogenin-2 (NGN2) transcription factor (page 26, section BASIC PROTOCOL 5: DIFFERENTIATION OF i3NEURONS).
Also, Neyrinck et al. teaches that functionally mature human astrocytes can be generated by SOX9 overexpression for 6 days in pluripotent stem cell (PSC)-derived neural progenitor cells (Abstract).
Furthermore, García-León et al. teaches that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive oligodendrocytes (Ols) from hPSCs in only 22 days (Abstract).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have modified the method of preparing the in vitro culture of Wicks et al. to include inducing iPSC, transfected with an inducible NGN2 transgene, into neuronal cells, inducing iPSC, transfected with an inducible SOX9 transgene, into astrocytes, inducing iPSC, transfected with an inducible SOX10 transgene, into oligodendrocytes and cultivating them, respectively and combining them with a reasonable expectation of success. One would have been motivated to have done so in order to generate an in vitro culture expressing the desired transgenes since NGN2 promotes neural cells differentiation, SOX9 promotes astrocytes differentiation, and SOX10 promotes oligodendrocytes differentiation as taught by Fernandopulle et al., Neyrinck et al., and García-León et al., respectively.
Regarding claim 17: Following discussion of claim 16 above, Wick et al. teaches that the combined cells are grown as a three-dimensional cell culture (page 14, Example 4).
Regarding claim 18: Following discussion of claim 16 above, Wick et al. teaches detecting a penetration of the compound through the endothelial layer and/or other physiological response (e.g., damage, scar tissue formation, infection, cell proliferation, bum, cell death, marker release such as histamine release, cytokine release, changes in gene expression (page 8, lines 33-34 and page 9, lines 1-4).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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