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 .
Election/Restrictions
Applicant's election with traverse of Group 1, claims 1-6 drawn to a pharmaceutical composition comprising a neural precursor cell differentiated from an HLA homozygous human induced pluripotent stem cell in the reply filed on July 6, 2026 is acknowledged. The traversal is on the ground(s) that claims were not interpreted in light of the description and that unity of invention exists between Groups 1 and 2 as the groups share a technical relationship which involves the same special technical feature. Applicant points to MPEP 806.03 and 803 regarding determination of distinctness as indicating that that the burden for unity of invention per MPEP 1893.03(d) has not been met.
This is not found persuasive because the examiner was able to provide art which satisfied the limitations of the product of group 1, thereby demonstrating that the special technical feature of a neural stem/progenitor cell derived from an HLA homozygous human induced pluripotent stem cell lacks novelty. Therefore, a lack of unity exists between the restricted groups (PCT Lack of Unity practice). Regarding Applicant’s traversal to distinctness and search burden, the restriction was not predicated on US practice (i.e. search burden). The application was filed under 371 practice so the criteria for restriction is lack of unity.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on July 6, 2021.
Newly submitted claims 11-15 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: newly submitted claims 11-15 also share the special technical feature of a neural precursor cell derived from an HLA homozygous human induced pluripotent stem cell which is known based on the prior art of record (Ozaki et al.) and therefore lacks novelty.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 11-15 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Priority
The instant application is a 35 U.S.C 371 national stage filing of the International Application No. PCT/KR2022/007500 filed on May 26, 2022. The instant application claims foreign priority under 35 U.S.C 119(a)-(d) to Korean Patent Application(s) KR10-2021-0068608, filed on May 27, 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 November 27, 2023 is in compliance with the provisions of 37 CFR 1.97 and is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites the abbreviation “HLA” without first defining the abbreviation with the full term. Terms should be introduced using the full term upon first usage followed by the abbreviation in paratheses. Appropriate correction is required. It is recommended that Applicant amend the claim to recite “human leukocyte antigen (HLA”).
Claim Interpretation
Claim 1 recites the limitation “for preventing or treating a stroke” which is considered to be an intended use of the composition comprising a neural precursor cell differentiated from an HLA homozygous human induced pluripotent stem cell which does not result in a structural difference in claimed neural precursor cell and therefore is not considered to limit the claim (See MPEP 2111.02(II).
Similarly, dependent claims 5 and 6 recite wherein clauses which are further limiting to the intended use but do not result in a structural difference in the composition and also are not considered to limit the claim.
Claim Rejections - 35 USC § 112(b)
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 1-6 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. Claims 5-6 are included in the rejection for incorporating limitations of a rejected base claim while failing to correct the deficiency.
Claim 1 recites the limitation “comprising an HLA homozygote as an active ingredient” which renders the scope of the claim indefinite. A homozygote is defined by the instant specification as a subject (Pg. 3, 1st full para.). As claimed, it appears that the HLA homozygous individual, and not the cells derived from an HLA homozygous individual, is the active ingredient in the pharmaceutical composition and it is not clear how a subject could be used as an active ingredient in a pharmaceutical composition. Appropriate correction is required.
Claim 2, which depends from claim 1, recites the limitation "the HLA homozygous" in line 2. Claim 1 both recites a “an HLA homozygous human induced pluripotent stem cell” and “an HLA homozygote”. As claimed it is unclear whether the recitation of “the HLA homozygous” is intended to refer to the HLA homozygous human induced pluripotent stem cell and lacks antecedent basis for this limitation or is a typographical error intending to refer to the HLA homozygote. Appropriate correction is required.
Claim 3, which depends from claim 1, recites the limitation "the human induced pluripotent stem cell" in line 2. There is insufficient antecedent basis for this limitation in the claim as the prior recitation is to an HLA homozygous human induced pluripotent stem cell and as claimed, it is unclear whether the instant recitation of the human induced pluripotent stem cell is intended to refer to the HLA homozygous human induced pluripotent stem cell or a different human induced pluripotent stem cell. Appropriate correction is required.
Claim 4, which depends from claim 1, recites the limitation "the neural progenitor cell" in line 2. There is insufficient antecedent basis for this limitation in the claim as the prior recitation is to “a neural precursor cell”. Appropriate correction 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 therefore, subject to the conditions and requirements of this title.
Claims 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claims recite a pharmaceutical composition comprising a neural precursor cell differentiated from an HLA homozygous human induced pluripotent stem cell. This judicial exception is not integrated into a practical application because the natural product is not linked to any particular technology. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional limitations beyond the naturally occurring product.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then does the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to Step 1, claims 1-6 are drawn to a composition of matter- a pharmaceutical composition comprising a neural precursor cell differentiated from an HLA homozygous human induced pluripotent stem cell.
In regard to Step 2A, Prong One, claims 1-6 are drawn to a nature-based product which is not markedly different from its naturally occurring counterpart. Specifically, independent claim 1 is directed to a composition comprising a neural precursor cell differentiated from an HLA homozygous human induced pluripotent stem cell. Dependent claims 2-4 recite that the HLA homozygous human induced pluripotent stem cell is homozygous for HLA-A, HLA-B, and HLA-DRB1, that the HLA homozygous human induced pluripotent stem cell is derived from a cord blood mononuclear cell or a peripheral blood mononuclear cell, and that the neural precursor comprises a Sox2, Nestin, or Musashi genes, respectively. Dependent claims 5 and 6 recite the intended use of the pharmaceutical composition.
The instant specification indicates that the neural precursor cells are derived from subjects who are homozygous for specific gene (Pg. 3, 1st full para.) and that the cells used to generate induced pluripotent stem cells can be derived from naturally occurring cord blood mononuclear cells or peripheral blood mononuclear cells (Pg. 3, 6th para.) or from somatic cells donated by human subjects (Pg. 3, 2nd para.). Thus, the instant invention of the claims is a naturally occurring product. Because instant claims are directed to a nature-based product, i.e., neural precursor cell differentiated from an HLA homozygous human induced pluripotent stem cell, the nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterparts in their natural state.
The instant specification discloses that induced pluripotent stem cells can be dedifferentiated via a non-virus dedifferentiation factors comprising a protein, cell extract, compound, etc. These differentiation methods are considered to be non-integrating and therefore related to transient exposure of naturally occurring cells to dedifferentiation factors which a skilled artisan would expect to not result in structural differences between the induced pluripotent stem cells and naturally occurring stem cells which can both become neural precursor cells. Further, the instant specification discloses that induced pluripotent stem cells have “almost the same properties” as embryonic stem cells including cell shape, gene and protein expression patterns, pluripotency, teratoma formation, the ability to generate chimeric mice, and germline transmission of genes (Pg. 3, last para.) also indicating a lack of markedly different characteristic from naturally occurring counterparts in their natural state.
Applicant is directed to the publication of Rim et al. (2018, Recent progress of national banking project on homozygous HLA‐typed induced pluripotent stem cells in South Korea. J. of Tissue Eng. and Reg. Med., 12(3), e1531-e1536.) which discloses, prior to the date of the instant invention, generation of a bank of homozygous HLA hi-PSCs for clinical use (Abstract). Rim et al. discloses hiPSC lines derived from peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CMBCs) (Pg. e1532, right col., 2nd to last para.) from donors with various HLA-homozygous types (see Table 1 and Table 2). Rim et al. discloses that the iPSCs are integration free (Pg. e1535, left col., 1st half of para. also See Fig. 1), maintain an undifferentiated state, normal karyotypes, and can generate into all three germ layers (Pg. e1535, left col., 2nd half of para), similar to naturally occurring embryonic stem cells (Pg. e1532, left col., 1st para.).
Applicant is also directed to the publication of Yu et al. (2009, Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324(5928), 797-801) which discloses that, prior to the date of the instant invention, hiPSCs could be reprogrammed using integration free episomal vectors and generate hiPSC cells which are similar to embryonic stem cells (Abstract). Yu et al. discloses that hiPSC colonies generated by episomal vectors (Pg. 798, left col., 1st full para.) exhibit typical human embryonic stem cell morphology, gene expression profiles, and ability to form teratomas comprising cells of all primary germ layers (Pgs. 799-800, bridging para.). Yu et al. further discloses that vector-free hiPSC subclones could be selected (Pg. 800, left col., last para.) and that the subclones were morphologically similar to human embryonic stem cells, had normal karyotypes, similar cell surface marker expression, gene expression, and differentiation patterns as embryonic stem cells (Pg. 800, center col., full para.).
Therefore, as the prior art indicates that there is no structural difference between embryonic stem cells and the hiPSCs reprogrammed via non-integrating methods, that is, the starting cell for neural precursors, a skilled artisan would also expect that there would also be no structural difference between neural precursor cells derived from hiPSCs compared to those which are naturally occurring and differentiated from embryonic stem cells. Because there is no difference between the claimed neural precursor cells and naturally occurring neural precursor cells, the claimed cells do not have markedly different characteristics, and thus are a “product of nature” exception. Accordingly, instant claims are directed to a judicial exception.
In regard to Step 2A Prong Two, the judicial exception is not integrated into a practical application. Claim 1 recites the additional limitation of the naturally occurring product in a pharmaceutical composition. The term pharmaceutical composition is extremely broad and encompass many embodiments including, per the instant specification, “the active ingredient alone” (Pg. 5, 5th para.). Thus, the pharmaceutical composition as instantly claimed can be solely the naturally occurring product which does not add any limitations beyond the naturally occurring product.
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As stated supra, claim 1 recites no additional meaningful elements to the neural precursor cell. As discussed above with respect to integration of the natural product into a practical application, the additional element of formulation as a pharmaceutical composition encompasses embodiments amounting to no more than the neural cell thus do not provide inventive concepts.
Therefore, claims 1-6 are directed to a natural cell product, that is not markedly different from its natural counterpart, is not integrated into a practical application, and does not include elements that amount to significantly more than the natural product itself and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
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 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ozaki et al. (2017, Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro. Stem Cell Res., 19, 128-138, hereafter “Ozaki”) as evidenced by Mercurio et al. (2019, More than just Stem Cells: Functional Roles of the Transcription Factor Sox2 in Differentiated Glia and Neurons. Int J Mol Sci. 20(18): 4540, hereafter “Mercurio”).
With regard to claim 1, Ozaki discloses neural stem/progenitor cells (NS/PCs) differentiated from human induced pluripotent stem cells (hi-PSCs) from an HLA homozygous donor, i.e. hi-PSC-NC/PCs (Pg. 129, left col., last para.). As the instant specification indicates that the pharmaceutical composition can be nothing more than the “active ingredient” (Pg. 5, 5th para.) which is defined as neural precursor cells differentiated from an HLA homozygous hi-PSC (Pg. 2, 1st para.), Ozaki’s disclosed hi-PSC-NC/PCs are considered to reasonably read on a pharmaceutical composition comprising neural precursor cells differentiated from an HLA homozygous hi-PSC.
With regard to claims 2 and 3, Ozaki discloses that the hiPSC line was derived from PBMCs of a donor homozygous for HLA-A, HLA-B, and HLA-DRB1 (Pg. 129, left col., last para.).
With regard to claim 4, Ozaki is silent as to the expression of Sox2, Nestin, or Musashi however, Mercurio evidences that Sox2 can be used to reprogram differentiated cells to induced pluripotent stem cells and is highly expressed in neural stem cells/progenitor cells (Pg. 1, last para.) as well as many differentiated neuronal cells (Table 1).
With regard to claims 5 and 6, as detailed supra in the claim interpretation section, the recitation of “for preventing or treating a stroke” is considered to be an intended use of the pharmaceutical composition comprising neural precursor cells differentiated from an HLA homozygous hi-PSC which does not result in a structural difference in claimed neural precursor cell and therefore is not considered to limit the claim. Therefore, as the wherein clauses recited in claims 5 and 6 are directed to the intended use of the composition and also do not affect the structure, they are similarly not considered to limit the claim (See MPEP 2111.02(II).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631
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