DETAILED ACTION
Notice of Pre-AIA of 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 .
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-7 in the reply filed on April 24, 2026 is acknowledged.
Claims 8-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 24, 2026.
Priority
The instant application is a 35 U.S.C 371 national stage filing of the International Application No. PCT/KR2021/012183 filed on September 8, 2021. The instant application claims foreign priority under 35 U.S.C 119(a)-(d) to Korean Patent Application(s) KR10-2020-0116430, filed on September 10, 2020 and KR10-2021-0009498, filed on September 22, 2021. Receipt is acknowledged of a certified copy of the foreign patent application in the original language as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 9, 2023 is in compliance with the provisions of 37 CFR 1.97 and is being considered by the examiner.
Applicant is reminded that 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.
Objections to the Drawings
The drawings are objected to because at least the following issues have been found:
FIGs. 1A and 1B appear to reference fluorescent immunostaining (Pg 16, 1st para.) showing coexpression or overlay of markers, however the images are in black and white.
FIG. 2B also appears to reference fluorescent immunostaining (Pg 16, 2nd para.) showing coexpression or overlay of markers, however the images are in black and white.
FIGs. 2B and 2D are detailed as a comparison of the number of undifferentiated neural precursor cells at 14 days after introduction of NFIB compared to NFIB and SOX9 (Pg. 16, 3rd para.)
FIG. 2D is detailed in the same paragraph (Pg. 16, 3rd para. ) as depicting RT-PCR analysis of SOX9 expression. Appropriate correction is required.
FIG. 2F appears to reference fluorescent immunostaining (Pg. 17, 1st para.) showing coexpression or overlay of markers, however the images are in black and white.
FIG. 3A and 3B appear to reference fluorescent immunostaining (Pg. 17, 2nd para.) showing coexpression or overlay of markers, however the images are in black and white.
FIG. 4A (panels A, B, and D) appear to reference fluorescent immunostaining (Pg. 17, 3rd para.) showing coexpression or overlay of markers, however the images are in black and white.
FIG. 4C appears to contain a color-coded legend while the images are in black and white.
FIGs 4D, 5B, 5C, 6B, 7B, and 7F all appear to contain heatmaps which are in black and white rendering them illegible.
FIG 5D contains a legend that does not differentiate between the instant disclosure and previous studies.
FIGs 6E and 6F are disclosed as indicating fluorescence ratios from individual cells. The images are in black and white rendering them illegible (Pg. 19).
FIG. 7C appears to reference fluorescent immunostaining (Pg. 20, full para.) showing coexpression or overlay of markers, however the images are in black and white.
FIG. 8D appears to reference fluorescent immunostaining (Pg. 21) showing coexpression or overlay of markers, however the images are in black and white.
This is not intended to be an exhaustive list. It is recommended that Applicant review all drawings to ensure they comply with office guidelines.
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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Objections to the Specification
The use of the term StemMACS (Pg. 22), IRES-Puro (Pg. 23), TetO-FUW-DLX2-IRES-hygro (Pg. 24), Alexa Fluor (Pg. 29), which are a trade names or a marks used in commerce, have 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 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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Claim 1 is drawn to a composition comprising an NFIB protein or a gene encoding the same.
Claims 2-7, which depend from claim 1, are drawn to a vector which can be used to introduce a gene encoding the NFIB protein (claims 2-3), limitations regarding neural precursor cells (claims 4-6), and limitations regarding the timeline of differentiation.
Claims 1-7 are drawn to a statutory category of invention, a product, under Step 1.
The claims recite a composition comprising an NFIB protein or a gene encoding the same. The instant specification discloses that the NFIB gene and protein are derived from mammals such as mice, rats, apes, or humans and that the full-length NFIB gene and protein can be used (Pg. 4, last para.)
Thus, claims 1-7 are drawn to the judicial exception of a product of nature without markedly different characteristics under Step 2A, Prong 1.
This judicial exception is not integrated into a practical application under Step 2A, Prong 2 because although claim 1 recites a composition “for inducing differentiation from neural precursor cells into astrocytes”, this recitation is considered to be a statement of intended use of the composition comprising an NFIB protein or gene encoding the same. Per MPEP 2111.02(II), it does not appear that the recitation of “for inducing differentiation from neural precursor cells into astrocytes” impart a structural difference in the claimed composition comprising an NFIB protein or gene encoding the same and therefore do not serve to limit the claim, absent evidence to the contrary. Claims 2 and 3 recite limitations regarding a vector used to introduce a gene encoding the NFIB protein which is considered to recite product-by-process limitations. The claimed process by which the composition comprising and NFIB protein or gene encoding the NFIB protein does not appear to impart a structural difference to the claimed composition. See MPEP 2113(I) which states:
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”
Likewise, claims 4-6 recite limitations regarding characterization of neural precursor cells, and claim 7 recites limitations regarding the timeline for differentiation, which are considered to be wherein clauses which are not limiting the structure in the broadly claimed composition comprising an NFIB protein or a gene encoding the same.
Under the holding of Myriad, this isolated but otherwise unchanged nucleic acid is not eligible because it is not different enough from what exists in nature to avoid improperly tying up the future use and study of naturally occurring NFIB gene. In other words, the claimed nucleic acid is different, but not markedly different, from its natural counterpart in its natural state, and thus is a “product of nature” exception. Accordingly, the claim is directed to an exception under Step 2A, Prong 1).
In regard to Step 2A, Prong 2, instant claims are directed to said nucleic acid in a vector. With respect to Step 2A, Prong 2, limitations that may be enough to qualify as additional elements that integrate the judicial exception into a practical application include:
Improvements to another technology or technical field.
Improvements to the functioning of the computer itself.
Applying the judicial exception with, or by use of, a particular machine.
Effecting a transformation or reduction of a particular article to a different state or thing
Adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application.
Other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
With respect to Step 2A, Prong 2, limitations that were found not to be enough to qualify as additional elements that integrate the judicial exception into a practical application include:
Adding the words ‘‘apply it’’ (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well understood, routine and conventional activities previously known to the industry
Adding insignificant extrasolution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea
Generally linking the use of the judicial exception to a particular technological environment or field of use.
In regard to Step 2A, Prong 2, instant claims do not recite additional elements or a combination of elements in the claims other than the natural product itself. Specifically, claims 2 and 3, recite a “vector”, and claim 3, further describes the vector as a “episomal”. However, placing nucleic acids in a “vector” that is “episomal” (i.e., not in a chromosome) as claimed with such a high degree of generality encompasses natural expression systems of a native host cell (e.g., a mRNA).
Finally, in regard to Step 2B, does the claim recite additional elements that amount to significantly more than the judicial exception. In instant case, generic vectors were well-understood, routine and conventional in the art at the time of the invention. Viewed as a whole, these additional claim elements do not provide meaningful limitations to transform the natural product into a patent eligible composition.
Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims to not recite additional elements beyond an NFIB protein which is a naturally occurring protein or well-understood, routine, and conventional generic vectors under Step 2B.
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.
Claims 1-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Caiazzo et al. (2015, Direct conversion of fibroblasts into functional astrocytes by defined transcription factors. Stem Cell Reports, 4(1), 25-36 and supplemental information, hereafter “Caiazzo”) as evidenced by Fabra-Beser et al. (2021, Differential expression levels of Sox9 in early neocortical radial glial cells regulate the decision between stem cell maintenance and differentiation. J. Neurosci., 41(33), 6969-6986, hereafter “Fabra-Beser”) and Yeon et al. (2021, NFIB induces functional astrocytes from human pluripotent stem cell‐derived neural precursor cells mimicking in vivo astrogliogenesis. J. Cell. Phys., 236(11), 7625-7641, hereafter “Yeon”).
With regard to claim 1, the limitation “for inducing differentiation from neural precursor cells into astrocytes” is considered to be an intended use of the claimed composition which, as instantly claimed, is so broad that it is not limiting to the structure of the composition absent evidence to the contrary. Per MPEP 2113(I), recitation of intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.
However, in the event that the intended use does impart a structural difference in the composition, Caiazzo discloses a reprogramming cocktail comprising NFIB which can be used to quickly (within approx. two weeks) generate induced astrocytes (Pg. 26, left col., 1st para. and Pg. 27, left col., last para.). Caiazzo discloses that the Nfib gene was expressed in cortical progenitor cells (Pg. 27, left col. last para.) which is considered to reasonably read on neural precursor cells, which activated astrocytic gene program in neuronal precursor cells (Pg. 27, right col., last para.).
With regard to claims 2 and 3, Caiazzo teaches that the gene encoding the NFIB protein is comprised in a viral vector (Pg. 32, right col, Molecular Cloning and Viral Infection) which is used to deliver the gene to the neural precursor cells (Supplemental Information, Pg. S10, In utero electroporation).
With regard to claim 4, as detailed above, Caiazzo discloses differentiation of neural precursor cells (Pg. 27, left col. last para.). All cells including neural precursor cells are derived from pluripotent stem cells (e.g., embryonic stem cells).
With regard to claim 5, while Caiazzo is silent as to the endogenous expression of SOX9 in neural precursor cells, cortical progenitor cells endogenously express SOX9 as evidenced by Fabra-Beser. Caiazzo discloses that the vectors comprising Nfib were delivered to neural precursor cells, specifically RGCs (i.e., radial glial cells) (Supplementary Information, Pg. S10, In utero electroporation). Fabra-Beser evidences that SOX9 is widely expressed in RGCs (Pg. 6982, right col, last para.).
With regard to claim 6, while Caiazzo is silent as to upregulation of endogenous SOX9 expression, upregulation of endogenous SOX9 expression in neural precursor cells due to overexpression of NFIB appears to be an inherent property of the claimed composition as evidenced by Fabra-Beser and Yeon. Caiazzo discloses that vectors comprising Nfib were delivered to neural precursor cells, specifically RGCs (Supplementary Information, Pg. S10, In utero electroporation). Fabra-Beser evidences that SOX9 is widely expressed in RGCs (Pg. 6982, right col, last para.) and Yeon evidences that overexpression of NFIB in neural precursor cells results in upregulation of endogenous SOX9 expression (Pg. 7630, left col., 1st para.). See MPEP 2112.01(II).
With regard to claim 7, Caiazzo teaches that astrocyte differentiation is performed within three weeks (Pg. 26, left col., 1st para. and Pg. 27, left col., last para.).
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Sun et al. (US 20180072988) teaches a method of converting a stem cell into a lineage specific cell comprising transfecting a stem cell with at least one expression vector comprising at least one lineage reprogramming factors (Paras. [0007-0008]). Sun et al. teaches that the stem cells can be pluripotent stem cells (Para. [0037]) including embryonic stem cells and induced pluripotent stem cells (Para. [0069]) and the lineage specific cell can be an astrocyte (Para. [0072]). Sun et al. teaches that the reprogramming factor can be NFIB (Para. [0078]) and that the expression vector can be a viral vector (Para. [0067]).
Conclusion
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/ERIN V PAULUS/
Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631
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