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 .
Status of the Claims
Claims 13-18, 24-25, and 28-38 are pending (claim set as filed on 01/13/2026).
Election/Restrictions
Applicant’s election of Group I, product claims, in the reply filed on 01/13/2026 is acknowledged. Because Applicant 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)).
Method claims 24-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Therefore, only product claims 13-18 and 28-38 are presented for examination.
Priority
This application is a DIV of application no.: 15/048,789 (now U.S. Patent no. 11,674,123), which has a PRO 62/118,553 filed on 02/20/2015.
Drawings
The drawings filed on 05/01/2023 have been accepted.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 05/01/2023 and 10/21/2023 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Abstract Objection
The abstract of the disclosure is objected to because it does not comply with the proper language and format (see MPEP 608.01(b)). Appropriate correction is required.
Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as “means” and “said” should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns”, “The disclosure defined by this invention”, or “The disclosure describes”, etc.
Claim Interpretation
Claims 13-18’s recitation of “A substantially pure, isolated population of arterial endothelial cells” denotes that the claims, as a whole, are drawn to product claims where “For products, the claim limitations will define discrete physical structures or materials” (MPEP 2103(I)(C)). However, the claims’ phrases of “obtained by culturing … whereby a cell population comprising arterial endothelial cells is obtained” invokes the interpretation of product-by-process limitations where “Even 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” (MPEP 2113). Furthermore, dependent claims 31 and 34-38 are embodiments of the product-by-process limitations that further describe the conditions or steps of culturing.
Claim Rejections - 35 USC §101, Subject Matter Eligibility
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 13-18 and 30-38 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revised Patent Subject Matter Eligibility Guidance).
STEP 1: Is the claim directed to a process, machine, manufacture, or a composition of matter?
YES, the claims are directed to a composition of matter.
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES, the claims are considered to be “product of nature” exceptions. The courts have held that “products of nature” fall under the laws of nature and/or natural phenomena exceptions.
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the additional elements or a combination of elements in the claims does not impose a meaningful limit on the judicial exception. Note that the markedly different characteristics analysis is used to determine if a nature-based product is a “product of nature” exception. Thus, the markedly different characteristics analysis is part of Step 2A, i.e., it helps answer the question of whether a claim is directed to an exception as further explained below.
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to a law of nature and/or natural phenomena (i.e., a product of nature) without significantly more. Note that the claims must be interpreted under the broadest reasonable interpretation (BRI) standard when evaluating for a marked difference. Under BRI, the claims broadly read on a naturally occurring cell or at least one that substantially resembles thereto:
the instant specification discloses that the term “arterial endothelial cell” (AEC) refers to cells of the arterial vascular endothelial lineage (see instant pre-grant specification at ¶ [0031]).
phenotype: the specification discloses that the cells of the claimed invention are produced to be substantially genetically identical to their respective differentiated somatic cell of origin and display characteristics similar to higher potency cells (see specification at ¶ [0052]-[0053]).
function: the specification discloses that the obtained AECs exhibit arterial-specific functional characteristics (e.g., nitric oxide production, oxygen consumption rates, elongation in response to shear stress, low levels of TNFα-induced leukocyte adhesion) similar to primary arterial endothelial cells (see instant specification at ¶ [0099]).
structure: McCloskey (US 2012/0064040 A1) teaches “an arterial endothelial cell is a specialized endothelial cell population that lines the lumen of arteries. Both arterial and arterial progenitors will express varying levels of the aforementioned markers and will also express of the following arterial EC markers: Alkl, Bmx, CD44, Connexin37, Connexin40, CXCR4, Delta-like 4, Depp, ephrinB2, GFBP-5P, Jagged1, Neuropilin1, Notch1, Notch4, and Unc5b” (see ¶ [0050], [0112]).
There is no indication that the claimed composition has any markedly different characteristic (e.g., structure, function, phenotype, etc.) that is different than what is found in nature. Thus, it appears that Applicant is claiming a naturally occurring product or at least one that is not patentably distinct therefrom.
Therefore, the claims are interpreted under the BRI standard, wherein the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite any additional elements.
Therefore, the claims, as a whole, are considered as products of nature which are directed to judicially recognized exceptions without amounting to significantly more from what occurs in nature and thus, are not eligible subject matter under 35 U.S.C. §101.
Claim Rejections - 35 USC §102-103, Anticipation/Obviousness
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 13-18 and 30-38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated, or in the alternative, under 35 U.S.C. 103 as being unpatentable over McCloskey (US 2012/0064040 A1 - cited in the IDS filed on 05/01/2023).
McCloskey’s general disclosure relates to the field of derivation of endothelial cells from embryonic stem cells using a serum free chemically defined medium (see abstract & ¶ [0003]).
Regarding base claims 13 and 16, McCloskey teaches methods that are particularly useful for preparing a population of endothelial cells (e.g., vascular or arterial endothelial cells) wherein the method comprises differentiating embryonic stem cells by culturing said stem cells in a chemically defined medium that is serum-free wherein the medium comprises vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), amino acids, antibiotics, and admixed in a basal medium of DMEM (see ¶ [0090]-[0091], [0104]-[0106], [0013]). McCloskey discloses that the cells are cultured under conditions (temperature, growth, or culture medium) and for an appropriate amount of time to attain exponential proliferation and further discloses that induction times varies between cell lines; cells were allowed to grow up for at least 7 days (see ¶ [0099], [0103], [0105]).
Regarding the claims’ limitations pertaining to the arterial endothelial cell expression markers and percentage population, McCloskey teaches “an arterial endothelial cell is a specialized endothelial cell population that lines the lumen of arteries. Both arterial and arterial progenitors will express varying levels of the aforementioned markers and will also express of the following arterial EC markers: Alkl, Bmx, CD44, Connexin37, Connexin40, CXCR4, Delta-like 4, Depp, ephrinB2, GFBP-5P, Jagged1, Neuropilin1, Notch1, Notch4, and Unc5b” (see ¶ [0050], [0112]) and venous endothelial cells have the Eph4 expression marker (see [0051]). McCloskey further teaches a range of obtaining a substantially homogeneous cell population which describes a population of cells in which more than about 80% of the cells are of the same or similar phenotype (see ¶ [0041]).
Regarding claims’ limitations pertaining to the mesodermal cells, McCloskey teaches an induction stage of culturing murine embryonic stem cells in the chemically defined medium comprising FGF, VEGF, bone morphogenetic protein 4 (BMP) for 2-5 days wherein BMP-4 and Activin A succeed in promoting mesodermal specific gene expression in serum free differentiation conditions (see ¶ [0116]-[0119], [0104]-[0106]). Activin A is known to enhance mesoderm induction (see ¶ [0058]). McCloskey teaches a mesodermal progenitor cell is a cell that is committed to the mesodermal lineage, as opposed to ectoderm or endoderm. Mesodermal tissues include muscle, cardiovascular tissue, and hematopoietic cells. Markers for identification of a mesodermal progenitors include but are not limited to: Flk-1, Brachyury, CD31 (PECAM1), CD325 (M-cadherin), CD34, (Mucosialin), NF-YA and Sca-1 (Ly6A/E) (see ¶ [0053]).
Regarding claims’ limitations pertaining to the type of pluripotent cells, McCloskey teaches differentiating an isolated embryonic stem cell, an embryoid body, a parthenogenetic stem cell or an induced pluripotent stem (iPS) cell to an endothelial cell progenitor or an endothelial cell or a population of endothelial progenitors or endothelial cells. The isolated stem cell is of animal origin, e.g., a mammalian cell, e.g., a human cell, a simian cell, a bovine cell or a murine cell (see ¶ [0017], [0033], [0047], [0073]).
Anticipation: the cited reference of McCloskey discloses a product which appears to be identical to the presently claimed product, based on the fact that McCloskey teaches a cell population of arterial endothelial cells (AEC) with overlapping characteristics as recited in the claims, and on the fact that McCloskey discloses a product made by the same basic series of steps as recited in the claims. Consequently, the claimed product appears to be anticipated by the reference.
Obviousness: however, even if the reference product and the claimed product are not one and the same and there is, in fact, no anticipation, the reference product would, nevertheless, have rendered the claimed product obvious to one of ordinary skill in the art at the time the claimed invention was filed in view of the fact that any nominal difference between the products would appear to be reasonably expected variances due to experimental error or batch-to-batch inconsistencies in the starting material. McCloskey’s arterial endothelial cells appear to be substantially similar to the claimed product such that the differences are minor and do not arise to level of patentable significance or distinction. Thus, the claimed invention as a whole was clearly prima facie obvious especially in the absence of sufficient, clear, and convincing evidence to the contrary.
The use of 35 U.S.C. §102 and §103 rejections for product-by-process claims has been approved by the courts. “The lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith” (MPEP 2113: Product-by-Process claims).
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over McCloskey as applied to claims 13-18 and 30-38 above, and in view of Lian (Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling, published on 05/01/2023).
McCloskey’s teaching is discussed above but note that McCloskey teaches this invention also provides a cell culture system or “kit” comprising of the cell culture mediums as described above alone or in combination with each other; a cell culture container and instructions for culturing and differentiating the cells (see ¶ [0087]-[0089]). ATCC (evidence document) discloses that the formulation of DMEM is albumin-free and insulin-free (see page 1).
However, McCloskey does not teach: wherein the kit comprises a TGF-β inhibitor.
Lian’s general disclosure relates to a method to efficiently produce endothelial cells from human pluripotent stem cells (hPSC) via GSK3 inhibition and culture in defined media to direct hPSC differentiation to endothelial progenitors (see abstract). Lian teaches endothelial progenitors are derived from a subpopulation of mesoderm that co-expresses brachyury and teaches hPSCs cultured as embryoid bodies were exposed to a growth factor cocktail containing Activin A, BMP4, FGF2, and VEGF to induce differentiation to endothelial progenitors and teaches the TGF-β signaling inhibitor SB431542 promoted endothelial cell generation and expansion (see pages 804-805, adjoining ¶).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ a TGF-β inhibitor such as taught by Lian in McCloskey’s kit for producing arterial endothelial cells. The ordinary artisan would have been motivated to do so is because Lian teaches that a TGF-β inhibitor promoted endothelial cell generation and expansion. Thus, the ordinary artisan would have reasonably recognized that a TGF-β inhibitor is an advantageous additive for McCloskey’s purpose for inducing/directing the differentiation of pluripotent stem cells into endothelial cells as each of their function in influencing to endothelial cell lineage commitment are already known in the art. The ordinary artisan would have had a reasonable expectation of success because the references of McCloskey and Lian are both directed to culture media agents to produce endothelial cells from pluripotent stem cells.
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653