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 .
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/US2022/073548, filed
08 July 2022. Acknowledgment is made of Applicants’ claim for benefit under 35 USC 119(e) to US Provisional Application No. 63/313842, filed 25 February 2022, and US Provisional Application No. 63/219705, filed 08 July 2021.
Election/Restrictions
Applicants’ election of Group I, encompassing claims 1-2, 9-10, 12, 14-15, 68, 71-73, and 78 in the reply filed on 18 May 2026 is acknowledged. In addition, Applicants’ election of the pluripotent cell population species as having an overexpressed RFX4 transcription factor encoded by SEQ ID NOs: 106 and 280-282, as well as the election of the stem cell species expressing a combination of RFX4 (TFORF0190) and RFX4 (TFORT0192) is acknowledged. The requirement is still deemed proper and is therefore made FINAL. However, because Applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Accordingly, claims 17, 29, 33, 37, 41, 57, 65-66, 72 and 76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claim.
Therefore, claims 1-2, 9-10, 12, 14-15, 17, 29, 33, 37, 41, 57, 65-66, 68, 71-73, 76, and 78, of record 18 May 2026, are pending. Claims 17, 29, 33, 37, 41, 57, 65-66, 72 and 76 are withdrawn for
reading on the non-elected inventions and species. Prosecution on the merits commences for claims
1-2, 9-10, 12, 14-15, 68, 71, 73, and 78.
Drawings
The drawings filed 05 January 2024 are objected to because the lack of clarity of the images within Figures 4-7, 14A, 15B, 18C, 18E, 21C, 22B, 23, 27G, 30, 32D, 33A, 33G, 33J, 33K, 35C, 35E, 37E, 38A, 38D, 38E, 39A-E, 40E-J, 41E, 42C, 42D, 43D, 44B, 46C, 59B, 61E, 63C, 64A-D, 65C, 65F, 65I, 65J, 68A-E, 69K, 70A, 70D-G, 71K, and 73G does not allow for examination. See MPEP § 1825 and 1.84.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the Specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). More specifically, the PAM sequences in Table 15 (Paragraph [0359]) that are greater than four defined amino acids in length require sequence identifiers.
Required response – Applicant must provide:
A substitute Specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted Specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended Specification without markings (clean version); and
• A statement that the substitute Specification contains no new matter.
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. More specifically, sequence identifiers are required for those within the graphics of Figures 26A, 39F, and 68F.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute Specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted Specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended Specification without markings (clean version); and
• A statement that the substitute Specification contains no new matter.
Specification
The substitute Specification filed 18 May 2026 is acknowledged and entered into the application file.
The lengthy Specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicants’ cooperation is requested in correcting any errors of which Applicants may become aware in the Specification.
However, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in at least Paragraphs [0343], [0360], [0633], [0674], [0678], and [0682]. Applicants are required to delete the embedded hyperlink 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 instant Specification is also objected to for referencing colors within the figures, when colored drawings have not submitted in the application. More specifically, the Specification references colors at least within Paragraphs [0057], [0062], [0072], [0075], [0083], [0084], [0104], 0109], 0112] in reference to Figures 21, 26, 36, 39, 47-48, 68, 73, and 76. Applicants are requested to review the Specification to identify any additional references to colors within the drawings and delete as appropriate since black and white drawings are submitted. The Specification must be amended to delete reference to specific colors within the text of the Specification.
Appropriate correction is required.
Information Disclosure Statement
The listing of references in the Specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the Specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 2 and 73 are objected to because of the following informalities:
Regarding claim 2: The instant claim is objected to for reciting “wherein the one or more… are chosen from: …” instead of “wherein the one or more… are selected from the group consisting of: …” in Lines 4 and 11.
Appropriate correction is required.
Regarding claim 73: The instant claim is objected to for reciting “further comprising differentiation of a neural progenitor into a neuron, an astrocyte, and/or an oligodendrocyte” instead of “further comprising differentiation of [[a]]the neural progenitor into a neuron, an astrocyte, and/or an oligodendrocyte”.
Appropriate correction is required.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all “optional” limitations are not
required.
Furthermore, instant claims 9-10 and 14-15 are directed to products which utilizes product-by-process language. The limitations of the process of production are considered only in so far as the process of production imparts distinct structural or chemical characteristics or properties to the claimed product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP § 2113.
Instant claim 9 is directed to an isolated neural progenitor cell produced by the method of claim 2. With that, instant claim 10 is directed to a therapeutic composition or ex vivo system comprising the isolated neural progenitor cell of claim 9. In the instant case, the method of production does not impart a structural or chemical distinction to the neural progenitor cell, other than the expression of radial glial cell markers. Therefore, the claims will be interpreted as if a transcription factor-expressing neural progenitor cell produced by any method fulfills the limitations detailed in the instant claims.
Instant claim 14 is directed to an isolated neuron, astrocyte, or oligodendrocyte produced by the method of claim 12. With that, instant claim 15 is directed to a therapeutic composition or ex vivo system comprising the neuron, astrocyte, or oligodendrocyte of claim 14. In the instant case, the method of production does not impart a structural or chemical distinction to the neuron, astrocyte, or oligodendrocyte, as the forced expression of the transcription factor allows the neural progenitor cells to differentiate into a neuron, an astrocyte, or an oligodendrocyte. Therefore, the claims will be interpreted as if a transcription factor-expressing neuron, astrocyte, or oligodendrocyte produced by any method fulfills the limitations detailed in the instant claims.
Improper Markush
Claims 1-2, 9-10, 12, 14-15, 68, and 73 are rejected on the basis that they contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the Specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of instant claims 1-2 and 12 are improper because the alternatives defined by the Markush groupings do not share both a single structural similarity and a common use for the following reasons:
Independent claim 1 recites, in relevant part, “overexpressing one or more transcription factors encoded by one or more nucleotide sequences chosen from SEQ ID Nos: 1-3638 in a pluripotent cell population...”.
Instant claim 2 depends from parent claim 1 and further recites, in relevant part, optional transcription factors chosen from a broad set including RFX4, NFIB, ASCL1, PAX6, EOMES, FOS, OTX1, NFIC, LHX2, RCOR2, GLI3, NOTCH2, HELLS, BCL11A, HES1, FANCD2, SOX9, FEZF2, and TCF7L2.
Independent claim 12 similarly recites, in relevant part, expression of “one or more transcription factors encoded by one or more nucleotide sequences chosen from SEQ ID Nos: 1-3638...”.
The instant Specification as filed 18 May 2026 does not describe the recited alternatives as members of a single recognized structural class. Rather, the Specification describes a broad screening platform for identifying transcription factors capable of differentiating pluripotent cells into multiple different target cell types. For example:
Paragraph [0008] states that the invention provides screening platforms for identifying transcription factors (TFs) that drive differentiation of pluripotent stem cells into target cell types, and provides examples including neural progenitors/radial glia and cardiomyocytes.
Paragraph [0009] lists a heterogeneous set of TFs associated with neural progenitor/radial glia differentiation, including RFX4, NFIB, ASCL1, PAX6, EOMES, FOS, OTX1, NFIC, LHX2, FANCD2, NOTCH1, SMARCC1, ESR2, ESR1, MESP1, RCOR2, GLI3, NOTCH2, HELLS, BCL11A, HES1, SOX9, FEZF2, and TCF7L2.
Paragraph [0028] separately identifies MESP1, EOMES, and ESR1 for cardiomyocyte differentiation.
Paragraph [0126] describes a library of all annotated human TF splice isoforms.
Paragraphs [0128]-[0130] identify four TFs – RFX4, NFIB, PAX6, and ASCL1 – as candidates for induced neural progenitor differentiation, and indicate differing differentiation outcomes.
The figures and examples within the instant disclosure further show that different TFs and TF isoforms yield distinct expression signatures and distinct downstream differentiated populations. See, for example, Paragraphs [0049]-[0050], [0057]-[0058], [0065]-[0068], [0078]-[0081], and [0097]-[0099] respectively corresponding to Figures 13-14, 21-22, 29-32, 42-45, and 61-63, as well as Examples 1, 5, 6, 7, 12, 15, and 16 of the instant Specification filed 18 May 2026.
It is also of note that the claims encompass an extraordinarily large number of distinct combinations. More specifically, because claims 1 and 12 recite “one or more” transcription factors chosen from SEQ ID Nos: 1-3638, the claims cover not only 3,638 individual alternatives, but every possible non-empty combination thereof (i.e., 2^3638 - 1 combinations). Even restricting the analysis to only 2-member and 3-member combinations yields more than 6.6 million pairs and more than 8 billion triplets. Such combinatorial breadth is inconsistent with a proper Markush grouping and reinforces that the claims sweep together a vast, heterogeneous collection of screened TF candidates rather than a single recognized class. The instant Specification likewise teaches that different TFs and TF combinations produce different gene programs and differentiated outcomes. See, for example, Paragraphs [0033]-[0034], [0243]-[0244], [0572]-[0578], and Figures 48, 74, 75, and 76 of the instant Specification filed 18 May 2026.
Thus, the Specification supports that the recited alternatives are a screened collection of distinct transcription factors and isoforms associated with different differentiation programs, rather than a proper Markush genus united by a single shared structural feature and common utility.
Moreover, for the elected neural progenitor invention, the Specification filed 18 May 2026 repeatedly identifies RFX4 as a preferred transcription factor:
Paragraph [0009] states: “In preferred embodiments, RFX4 is overexpressed to produce the neural progenitors.”
Paragraph [0012] states: “In preferred embodiments, the neural progenitor cell was produced by overexpression of RFX4.”
Paragraph [0128] states that RFX4, NFIB, PAX6, and ASCL1 were identified, and further indicates that RFX4-derived iNPs gave rise to the highest proportion of CNS cell types.
Accordingly, the broad recitation of alternatives extending well beyond the elected RFX4 species constitutes an improper Markush grouping.
NON-ELECTED SPECIES NOT EXAMINED ON THE MERITS
Because Applicant elected only the RFX4 species for examination corresponding to SEQ ID NOs: 106 and 280-282, and because the claims as presented are drawn to an improper Markush grouping encompassing numerous non-elected alternatives, the non-elected species will not be further examined on the merits in this action. Examination on the merits is limited to the elected species only. See MPEP §§ 808.01(a) and 821.01.
To the extent Applicant seeks examination of the elected invention, Applicant may amend the claims to correspond to the elected species, e.g., by limiting the claims to RFX4 and/or the elected RFX4 SEQ ID NOs, rather than continuing to recite the broad alternative grouping.
It is of note that instant claims 9-10, 12, 14-15, 68, and 73 are not separately argued here, but to the extent their scope depends on claims 1-2 and 12, their examination likewise proceeds only insofar as they correspond to the elected species. The recited claims are also included within the rejection because they depend from or fully incorporate the limitations of claims 1, 2, or 12, and thereby inherit the deficiencies of the parent claim.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 2, 12, 14-15, 73, and 78 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 2 and 73: Instant claim 2 recites the limitation “wherein the one or more radial glial cell markers are chosen from: VIM… and PAX6, or NES… and PAX6” in Lines 4-10. The scope of the claim is indefinite, as the ordinary artisan would not be readily apprised to which listings the radial cell markers are selected from. Therefore, the metes and bounds of the claim cannot be determined.
Likewise, the instant claim recites the limitation “wherein the one or more transcription factors are chosen from: RFX4… and TCF7L2, or RFX4… PAX6” in Lines 11-14. The scope of the claim is firstly indefinite, as the ordinary artisan would not be readily apprised to which listings the transcription factors are selected from. The scope of the claim is further indefinite since the second listing of “RFX4, NFIB, ASCL1, PAX6” does not contain a conjunction between the recited transcription factors. Therefore, the metes and bounds of the claim cannot be determined.
Instant claim 73 is dependent upon claim 2 and fails to correct the deficiencies of the parent claim, thus rendering it indefinite as well.
Appropriate correction is required.
Regarding claims 12 and 14-15: Independent claim 12 is directed to a method of producing neurons, astrocytes and/or oligodendrocytes, comprising expressing one or more transcription factors encoded by one or more nucleotide sequences chosen from SEQ ID Nos: 1-3638 in the isolated neural progenitor cell of claim 9 and inducing spontaneous or directed differentiation of the isolated neural progenitor cells. The scope of the claim is indefinite, as it is unclear if the method is requiring the expression of an additional transcription factor within the isolated neural progenitor of instant claim 9, or is instead restating that the isolated neural progenitor is initially required to express the one or more transcription factors. Therefore, the metes and bounds of the claim cannot be determined.
Instant claims 14-15 are fully incorporate the limitations of independent claim 12 and fail to correct the deficiencies of the parent claim, thus rendering them indefinite as well.
Appropriate correction is required.
Regarding claim 78: The instant claim recites the limitation “expressing in the stem cell a double or triple combination of transcription factors selected from the clusters in Table 19C.” Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for Applicants’ convenience." See MPEP § 2173.05(s): Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). Therefore, the metes and bounds of the claim cannot be determined, thus rendering the claim indefinite.
Appropriate correction is required.
For the sake of compact prosecution, the instant claim will be interpreted as if a double or triple combination of the generic transcription factors comprised within a cluster are required, as Table 19C of the instant disclosure only designates the TF ORF label of each transcription factor within a cluster, wherein the TF ORF labels are listed in Table 3 of the instant disclosure as having a RefSeq Gene Name, and RefSeq and Gencode ID – which are separate from the ORF sequence SEQ ID that Applicants asserted within the species election.
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.
Claims 9-10 and 14-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nature-based products without significantly more.
Instant claim 9 is directed to an isolated neural progenitor cell produced by the method of claim 2. With that, instant claim 10 is directed to a therapeutic composition or ex vivo system comprising the isolated neural progenitor cell of claim 9. Instant claim 9 comprises a product-by-process limitation, as can be observed in the Claim Interpretation section above and is incorporated in its entirety herein.
Likewise, instant claim 14 is directed to an isolated neuron, astrocyte, or oligodendrocyte produced by the method of claim 12. With that, instant claim 15 is directed to a therapeutic composition or ex vivo system comprising the neuron, astrocyte, or oligodendrocyte of claim 14. Instant claim 14 comprises a product-by-process limitation, as can be observed in the Claim Interpretation section above and is incorporated in its entirety herein.
The test for 101 eligibility of judicial exceptions can be found at MPEP § 2106:
“First, the claimed invention must be to one of the four statutory categories. 35 U.S.C. 101 defines the four categories of invention that Congress deemed to be the appropriate subject matter of a patent: processes, machines, manufactures and compositions of matter.”
“Second, the claimed invention also must qualify as patent-eligible subject matter, i.e., the claim must not be directed to a judicial exception unless the claim as a whole includes additional limitations amounting to significantly more than the exception. The judicial exceptions (also called "judicially recognized exceptions" or simply "exceptions") are subject matter that the courts have found to be outside of, or exceptions to, the four statutory categories of invention, and are limited to abstract ideas, laws of nature and natural phenomena (including products of nature). Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 216, 110 USPQ2d 1976, 1980 (2014) (citing Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589, 106 USPQ2d 1972, 1979 (2013).”
“The Supreme Court in Mayo laid out a framework for determining whether an applicant is seeking to patent a judicial exception itself, or a patent-eligible application of the judicial exception. See Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. 66, 101 USPQ2d 1961). This framework, which is referred to as the Mayo test or the Alice/Mayo test, is discussed in further detail in subsection III, below. The first part of the Mayo test is to determine whether the claims are directed to an abstract idea, a law of nature or a natural phenomenon (i.e., a judicial exception). Id. If the claims are directed to a judicial exception, the second part of the Mayo test is to determine whether the claim recites additional elements that amount to significantly more than the judicial exception. Id. citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966). The Supreme Court has described the second part of the test as the "search for an 'inventive concept'". Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).”
Examiners should determine whether a claim satisfies the criteria for subject matter eligibility by evaluating the following steps outlined in a flow chart at MPEP 2106(III) and 2106.04(II)(A):
Step 1: is the Claim to a process, machine, manufacture or composition of matter? If Yes, proceed to Step 2A;
Step 2A, prong one: Is the Claim directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea? If Yes, proceed to Step 2A, prong two;
Step 2A, prong two: Does the claim recite additional elements that integrate the judicial exception into a practical application? If No, proceed to Step 2B;
Step 2B: Does the claim recite additional elements that amount to significantly more (an inventive concept) than the judicial exception? If No, the claim is not eligible subject matter under 35 USC 101.
With regard to Step 1: YES, the claims are each directed to a composition of matter, or product.
With regard to Step 2A, prong one: YES, the claims are directed to neural progenitors, neurons, astrocytes, or oligodendrocytes, and therapeutic compositions thereof, which are nature-based products. More specifically, since the instantly claimed neural progenitors, and neurons, astrocytes, or oligodendrocytes comprise product-by-process limitations – see Claim Interpretation section above – the claimed neural progenitors, neurons, astrocytes, and oligodendrocytes are compared to the closest naturally occurring counterpart, which are radial glial cell marker-expressing neural progenitors, and neurons, astrocytes, and oligodendrocytes, per se. Thus, there is no marked different between the claims and products of nature. See, for example, Pages 2-4 of Martinez-Cerdeño et al (Front Neuroanat, 2018). The same is true for the therapeutic compositions comprising either the neural progenitors, or neurons, astrocytes, and/or oligodendrocytes.
With regard to Step 2A, prong two: No, the claims do not include any additional elements that integrate the judicial exceptions into a practical application. Integration into a practical application requires additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception.
The claims do not modify or transform the naturally occurring neural progenitors, neurons, astrocytes, and oligodendrocytes, nor apply the cells for a particular treatment or medical condition, nor imposes a meaningful limit on the cells recited therein. In regards to the therapeutic compositions, having neural progenitors, and neurons, astrocytes, or oligodendrocytes comprised within a composition does not impose a meaningful limit on the judicial exception, as it is not structurally modifying the neural progenitors, neurons, astrocytes, and oligodendrocytes, nor integrating the neural progenitors, neurons, astrocytes, and oligodendrocytes into a practical application.
With regard to Step 2B: No, the claims do not provide any additional elements that amount to significantly more (an inventive concept) than the judicial exception.
Taken together, the claims encompass natural products. The judicial exception is not integrated into practical applications as iterated above. The claims do not include additional elements
that are sufficient to amount to significantly more than the judicial exception as iterated above.
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.
Claims 9-10 and 14-15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Niclis et al (US 2022/0389378 A1), with an effective filing date of 22 November 2019.
Niclis et al disclose methods for obtaining a neural microspheres, comprising the steps of culturing pluripotent stem cells (PSCs), differentiating the PSCs into neural stem precursor blast cells, aggregating the neural stem precursor blast cells to form a neural microsphere, allowing the neural stem precursor blast cells of the neural microsphere to further mature, and collecting the neural microsphere (Abstract; Paragraph [0037]).
As such, Niclis et al disclose human pluripotent stem cell-derived neural stem precursor blast cells – or neural progenitor cells – that express PAX6 (Paragraphs [0014], [0015], [0042], [0050], [0333]; Figures 1-2). Niclis et al further disclose that the neural progenitor cells are aggregated into an in vitro – or ex vivo – microsphere system (Paragraphs [0036]-[0038], [0049], [0051], [0057]-[0065], [0084]-[0085]).
Niclis et al further disclose the terminal differentiation of the neural progenitor cells into neurons (Paragraphs [0015], [0040], [0043], [0047], [0068], [0095]-[0098], [0306]-[0314]). Niclis et al further disclose that the neurons are comprised within a therapeutic composition (Paragraphs [0102]-[0108]).
Accordingly, Niclis et al anticipate the claims as follows:
Regarding claim 9: The instant claim comprises product-by-process. The effect of the product-by-process language is discussed above – see Claim Interpretation – and is incorporated herein in its entirety.
Accordingly, Niclis et al disclose human pluripotent stem cell-derived neural stem precursor blast cells – or neural progenitor cells – that express PAX6. As PAX6 is inherently a radial glial cell marker, this therefore reads on the isolated neural progenitor cell of the instant claim. See Paragraph [0015] of the instant disclosure.
Regarding claim 10: Following the discussion of claim 9, Niclis et al further disclose that the neural progenitor cells are aggregated into an in vitro – or ex vivo – microsphere system. This therefore reads on the ex vivo system of the instant claim.
Regarding claim 14: The instant claim comprises product-by-process. The effect of the product-by-process language is discussed above – see Claim Interpretation – and is incorporated herein in its entirety.
Accordingly, Niclis et al further disclose the terminal differentiation of the neural progenitor cells into neurons. This therefore reads on the isolated neurons of the instant claim.
Regarding claim 15: Following the discussion of claim 14, Niclis et al further disclose that the neurons are comprised within a therapeutic composition. This therefore reads on the therapeutic composition of the instant claim.
Claims 9-10, 14-15, 71, and 78 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Elkabetz et al (WO 2016/103269 A1, of record on IDS filed 05 January 2024).
Elkabetz et al disclose populations of neural cells and use of the populations and methods of producing same (Abstract).
As such, Elkabetz et al disclose a method of differentiating pluripotent stem cells into neural progenitor cells comprising overexpressing RFX4, wherein the neural progenitor cells express the early radial glial cell marker of PAX6 (Pages 5, 9, 11, 13-14, 38-39, 65, 123, 128). Elkabetz et al further disclose that various proteins of RFX4 effect the terminal differentiation of the pluripotent stem cells (Page 197; Table 4).
Elkabetz et al further disclose differentiating the neural progenitor cells into neurons and astrocytes (Pages 3-4, 20, 27-28, 47, 49-50, 52).
Elkabetz et al further disclose that the neural progenitor cells and differentiated neurons and astrocytes, are comprised within an in vitro – or ex vivo – cellular culture system (Pages 31-32, 106, 118-119, 122).
Accordingly, Elkabetz et al anticipate the claims as follows:
Regarding claim 9: The instant claim comprises product-by-process. The effect of the product-by-process language is discussed above – see Claim Interpretation – and is incorporated herein in its entirety.
Accordingly, Elkabetz et al disclose pluripotent stem cell-derived neural progenitor cells that express PAX6. As PAX6 is inherently a radial glial cell marker, this therefore reads on the isolated neural progenitor cell of the instant claim. See Paragraph [0015] of the instant disclosure.
Regarding claim 10: Following the discussion of claim 9, Elkabetz et al further disclose that the neural progenitor cells are comprised within an in vitro – or ex vivo – cellular culture system. This therefore reads on the ex vivo system of the instant claim.
Regarding claim 14: The instant claim comprises product-by-process. The effect of the product-by-process language is discussed above – see Claim Interpretation – and is incorporated herein in its entirety.
Accordingly, Elkabetz et al further disclose the terminal differentiation of the neural progenitor cells into neurons or astrocytes. This therefore reads on the isolated neurons or astrocytes of the instant claim.
Regarding claim 15: Following the discussion of claim 14, Elkabetz et al further disclose that the neurons or astrocytes are comprised within an in vitro – or ex vivo – cellular culture system. This therefore reads on the ex vivo system of the instant claim.
Regarding claim 71: Elkabetz et al disclose a method of differentiating pluripotent stem cells into neural progenitor cells comprising overexpressing RFX4. This therefore reads on the stem cell of the instant claim.
Regarding claim 78: Elkabetz et al disclose a method of differentiating pluripotent stem cells into neural progenitor cells comprising overexpressing different RFX4 proteins. Given the claim interpretation presented in the 35 USC 112(b) section above and Applicants’ species election, this therefore reads on the method of the instant claim.
Conclusion
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/ALYSSA G WESTON/Examiner, Art Unit 1633
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