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 .
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.
Claim Status
Claims 1-4, 6-7, 13, 15-18, 66, 69-73 are currently pending and examined on the merits.
Information Disclosure Statement
An IDS was received on 5/28/26. All references have been considered; however, due to the voluminous number of references in the IDS they have been only briefly considered. It is noted that the cloaking of a relevant reference by inclusion in a long list of citations may not comply with the Applicant’s duty of disclosure. Penn Yan Boats, Inc. v. Sea Lark Boats, Inc., 359 F. Supp. 948 (S.D. Fla. 1972). Therefore, the applicant is encouraged to present a concise statement as to the relevance of any particular documents known to be material for patentability as defined by 37 C.F.R. § 1.56.
Claim Objections
Claim 4 is objected to because of the following informalities. Appropriate correction is required.
Claim 4 appears to contain a typographical error and should read “IFNβ”.
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 4, 13, 15 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.
Claim 4 contains the limitation “further comprising at least one cytokine selected from IL-10 and IFNI3”. It is unclear if this limitation is indicating that the pluripotent stem cell (PSC) is combined with exogenous IL-10 or IFNβ or if the PSC is further engineered to express IL-10 or IFNβ. For examination purposes, this limitation is interpreted as the latter.
Claims 13, 15 contain the trademark/trade name PIGGYBAC® (Poseida Therapeutics, Delaware, US). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a particular transposase and, accordingly, the identification/description 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.
Claim(s) 70-73 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Erlich et al., US Publication No. 2019/0322981 (earliest priority date 7/5/16, hereinafter Erlich).
Regarding claim 70-73, Erlich discloses methods of generating oligodendral lineage precursor cells from pluripotent stem cells (PSCs) (Abstract). Erlich discloses genetically engineering PSCs to comprise the transcription factors SOX10, OLIG2, and NKX6.2 ([0008], claim 1). Erlich explains that the combination of the three transcription factors facilitates the rapid and efficient generation of human oligodendral lineage cells ([0008],[0071]-[0073], [0075]). Erlich discloses that SOX10 alone is sufficient to induce oligodendral specification ([0163], [0252]).
Therefore, every limitation of claims 70-73 is present in Erlich, and the subject matter is anticipated.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 6, 17-18, 66, 69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al., PCT Publication No. WO 2016/163958 (cited on IDS dated 5/28/26, hereinafter Sun)
Regarding claims 1, 66, Sun discloses methods of converting stem cells, such as human induced PSCs (iPSCs) into lineage specific cells (Abstract, [0017], [0019]-[0020]). Sun explains that traditional methods for converting stem cells into lineage specific cell types typically involves multiple intermediate stages requiring varying combinations of recombinant growth factors and small molecules, and eventually yield mixtures of both non-neuronal and neuronal cells with variable functional properties ([0005]). The timeline required to achieve the desired cell types may be a further limitation, taking as long as 30 weeks ([0005]). Sun discloses transfecting iPSCs with at least one expression vector operably linked to an inducible promoter ([0039]). In a preferred embodiment, the iPSCs are converted into a neural cell, such as an oligodendrocyte ([0051], [00107]). Neural transcription factors that may be used include be one or more of OLIG2, SOX9, NKX6.1, and NKX6.2 ([0058]). Following transduction, the resultant cells may be cultured ([00107]).
Regarding claim 6, Sun discloses the PSCs are genetically modified to express the transcription factors via retroviral, lentiviral, adeno-associated virus, sendai virus, or episomal DNA ([0046]-[0047], [0099]-[00103], [00107]-[00108]).
Regarding claims 17-18, Sun discloses that the stem cell may be an embryonic stem cell or iPSC ([0019]-[0021], [0049]).
Regarding claim 69, Sun further discloses preparing cell suspensions for administration to subjects ([00119]-[00121], [00150], [00153]).
Sun does not disclose that utilizing each of OLIG2, SOX9, NKX6.1, and NKX6.2. However, Sun discloses that the transcription factors may be selected from one or more of the transcription factors recited. Therefore, there is a suggestion present in Sun that a combination of OLIG2, SOX9, NKX6.1, and NKX6.2 could be utilized.
Regarding claim 7, Sun does not disclose that the PSC comprises five to fifty copies of at least one transcription factor. However, as per MPEP § 2144.04 duplication of parts is a considered a routine expedient requiring no more than ordinary skill in the art absent evidence to the contrary.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 1, 6, 17-18, 66, 69 above and in further view of Kim et al., (2015) Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model. The EMBO Journal, 34(22): 2971-2983 (cited on IDS dated 5/28/26, hereinafter Kim).
Sun does not disclose that PSC comprise the transcription factor OCT4.
Kim examines the use of Oct4 for induction of oligodendrocyte precursors (Abstract). Kim explains that oligodendrocyte precursor cells generated with a combination of transcription factors have limited expansion potential (Introduction). Kim discloses transfecting somatic cells with Oct4 (Generation of iOPCs, Generation of iOPCs from adult mouse fibroblasts by Oct4). Kim explains that that the resultant cells demonstrate bipotent differentiation potential (oligodendrocytes and astrocytes). Ki discloses that use of Oct4 allows for the large-scale expansion and culture of oligodendrocytes (Discussion). Kim further suggests that the disclosed methods may provide the basis for future oligodendrocyte generation (Discussion).
As both Sun and Kim are directed to methods of generating oligodendrocyte precursors, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to include the transcription factor Oct4 as taught by Kim in the methods of Sun to improve the expansion potential of the cells.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 1, 6, 17-18, 66, 69 above and in further view of Ryu et al., (2013) Gene therapy of multiple sclerosis using interferon ß-secreting human bone marrow mesenchymal stem cells. BioMed Research International, Vol. 2013, Article ID 696738 (cited on IDS dated 5/28/26, hereinafter Ryu).
Regarding claim 4, Sun does not disclose that a nucleic acid encoding IL-10, IFNβ, or a combination thereof is introduced into the PSC.
Ryu discloses that multiple sclerosis is an inflammatory disease in which central nervous system neurons are demyelinated (Introduction). Ryu explains that cell-based therapeutics which stimulate oligodendrogeneis and remyelination is desirable for treatment of MS (Introduction). Ryu further explains that IFN-β is a promising treatment modality (Introduction). Ryu discloses transfecting mesenchymal stem cells (MSCs) with IFN-β and administering to a mouse model of MS (Mesenchymal stem cell culture and adenovirus infection). Treatment with IFN-β transfected MSCs results in a significant amelioration of clinical symptoms and reduces demyelination (Clinical status of IFN-β secreting MSCs transplanted mice after EAE induction, MSC-IFN-β reduced inflammation and demyelination of lumbar spinal cords in EAE mice Figs. 2-3). Ryu concludes that IFN-B transfected MSCs may be effectively used for suppressing demyelination (Conclusions).
As both Ryu and Sun are directed to methods of genetically engineering stem cells it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to introduce a nucleic acid encoding IFNβ as per Ryu into the iPSC of the combination to further reduce demyelination and reduce clinical symptoms in treated subjects.
Claim(s) 1, 6-7, 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erlich as applied to claims 70-73 above, and in further view of Sun as applied to claims 1, 6, 17-18, 66, 69 above.
Regarding claim 1, Erlich discloses methods of generating oligodendral lineage precursor cells from PSCs (Abstract). Erlich discloses genetically engineering PSCs to comprise the transcription factors SOX10, OLIG2, and NKX6.2 ([0008], claim 1). Erlich explains that the combination of the three transcription factors facilitates the rapid and efficient generation of human oligodendral lineage cells ([0008],[0071]-[0073], [0075]).
Regarding claim 6, Erlich explains that introduction of nucleic acids into the PSC may be performed using any known methods for gene delivery ([0081]). Erlich discloses that the transcription factors may be encoded by a nucleotide sequence encoding the transcription factors (claim 14). The vector may be either a non-viral or a viral vector, such as a polycistronic lentiviral vectors ([0078]-[0081], [0229]-[0230], Fig. 2, claim 14).
Regarding claim 16, Erlich discloses that in some embodiments, the PSCs may further comprise a red fluorescent protein (RFP) ([0229], [0252]).
Erlich does not disclose that the PSC comprises at least four transcription factors OLIG2, SOX9, NKX6.1, NKX6.2, and OCT4.
Sun discloses methods of converting stem cells, such as human induced PSCs (iPSCs) into lineage specific cells (Abstract, [0017], [0019]-[0020]). Sun discloses transfecting iPSCs with at least one expression vector operably linked to an inducible promoter ([0039]). In a preferred embodiment, the iPSCs are converted into a neural cell, such as an oligodendrocyte ([0051], [00107]). Neural transcription factors that may be used include be one or more of OLIG2, SOX9, SOX 10, NKX6.1, and NKX6.2 ([0058]).
As both Erlich and Sun are directed to methods of producing oligodendrocyte precursor cells from PSCs, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would understand that the known neural transcription factors disclosed by Erlich and Sun could be combined to predictably produce a PSC comprising neural transcription factors which may be successfully differentiated into oligodendrocyte precursor cells.
Regarding claim 7, the combination does not disclose that the PSC comprises five to fifty copies of the nucleotide sequence encoding the transcription factor. However, as per MPEP § 2144.04 duplication of parts is a considered a routine expedient requiring no more than ordinary skill in the art absent evidence to the contrary.
Claim(s) 13, 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erlich in view of Sun as applied to claims 1, 6-7, 16 above, and in further view Li et al., (2017) One-step piggyBac Transposon-based CRISPR/Cas9 activation of multiple genes. Molecular Therapy, 8; 64-76 (hereinafter Li).
Regarding claims 13, 15, the combination does not disclose that the engineered nucleic acid is present on a PIGGYBAC® transposon vector, or that the PSC comprises a PIGGYBAC® transposase or a nucleic acid encoding the same.
Li discloses methods of using a piggyBac transposon-based CRISPR system for the generation of neural cells from iPSCs (Abstract). Li explains that lentiviral and retroviral vectors have a limited carrying capacity such that it is difficult to successfully introduce multiple transcription factors (Introduction). Li discloses using the piggyBac system to create all-in-one vectors including SOX10, OLIG2, SOX8 AND OLIG1 (All-in-one vectors for stable activation of multiple genes in single cells, Discussion, Fig. 4). Li discloses that the piggyBac system allows for rapid and stable activation of multiple transcription factors in iPSCs with improved activation magnitude as compared to one-by-one vectors (All-in-one vectors for stable activation of multiple genes in single cells, Discussion, Fig. 4).
As each of the references are directed to methods of genetically modifying PSCs to generate neural cells, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to use the piggyBac system of Li in the methods of the combination as an application of a known technique to a known method ready for improvement, to yield the predictable result of creating a PSC with stable activation of multiple neural transcription factors.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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