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 without traverse of Group I, claims 1-2, 4-13, 17, and 19-22, in the reply filed on 02/11/2026 is acknowledged.
Claims 3, 14-16, 18, and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups, there being no allowable generic or linking claim.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 02/11/2026.
Status of the Claims
Claims 1-23 are currently pending.
Claims 3, 14-16, 18, and 23 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-2, 4-13, 17, and 19-22 have been considered on the merits.
Specification
The use of a multitude of trademarks has been noted in this application at least on pgs. 24-25. The terms contain the appropriate symbols but are not accompanied by the generic terminology, which should be included. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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.
Claim 22 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. Based upon an analysis with respect to the claim as a whole, the claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below.
The claims are directed to:
Endothelial cells
There are no limitations in the claim that require the composition differ from endothelial cells found in nature.
The claims are directed to a composition of only a nature-based product, i.e., endothelial cells, this nature-based product is analyzed to determine whether it has markedly different
characteristics from any naturally occurring counterpart(s) in their natural state. In this regard, the
disclosed endothelial cells exist entirely in nature (e.g., same genotype and phenotype potential and structure).
The art, Beijnum et al (Nature Protocols, 2008) teaches the isolation of endothelial cells from fresh human tissues (abstract; pg. 1088, col. 1, para 2 “Reagent set up”).
The claims thus encompass endothelial cells that are identical (no difference in characteristics) to naturally occurring endothelial cells. Since there is no difference between the endothelial cells claimed and naturally occurring endothelial cells, the endothelial cells do not have markedly different characteristics, and thus are a “product of nature” exception. In re Roslin Institute (Edinburgh), 750 F.3d
1333, 1338-39 (Fed. Cir. 2014). Accordingly, the claimed invention is directed to an exception. Because
the claimed invention does not include any additional features that could add significantly more to the
exception, the claimed culture does not qualify as eligible subject matter, and should be rejected under
35 U.S.C. § 101.
PNG
media_image1.png
311
389
media_image1.png
Greyscale
Step 2A has recently been revised to include two prongs (Federal Register / Vol. 84, No. 4 / Monday, January 7, 2019):
PNG
media_image2.png
447
453
media_image2.png
Greyscale
An examination of Step 2A in the revised 101 guidance, with respect to the claimed invention, the answer is yes since the claimed invention comprises naturally occurring products (judicial exceptions), in the instant case these naturally occurring products are endothelial cells. When examining the claimed invention with regards to Step 2A prong 1, the answer is yes since the claimed invention encompasses naturally occurring products. When examining the claimed invention with regards to Step 2A prong 2, the answer is no since the claimed invention does not recite additional elements that integrate the judicial exception, in the instant case endothelial cells, into a practical application.
It is only the recited limitations in the claims that are examined under 101 and not aspects such as what the endothelial cells are capable of treating or used for (i.e. endothelial cells for testing). In this case only endothelial cells are examined with respect to its status as a judicial exception. It is again emphasized that the claimed invention is a composition and not a method.
An examination of Step 2B, the answer is no with respect to the claimed invention. There are no other additional elements recited in the claim that would amount to significantly more than the judicial exceptions. The endothelial cells as claimed encompasses a composition that is indistinguishable from those that exist in nature and there are no limitations that add any additional elements to the claimed endothelial cells. The endothelial cells has the same function as it does in nature and the fact that they may exist in an isolated system does not change the endothelial cells in a significant or meaningful way to amount to more than the judicial exception.
The only factors which can be examined under 101 in the claimed composition are those that are recited in the claim i.e. endothelial cells. How the endothelial cells were obtained and the knowledge of using them is not considered with respect to a composition claim, it is only the judicial exceptions themselves that are analyzed under 101 and in this case all of the components in the claimed composition are naturally-occurring products and thus qualifies as a judicial exception.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1-2, 4-13, 17, and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Thon et al (US20200138868A1), in view of Gerecht et al (US20180216063A1).
Claim interpretation: Claim 8 contains the limitation “wherein CHIR99021 is present in the culture medium at a concentration of about 36 µM”. The examples do not use a final concentration of 36 µM of CHIR99021, rather “36 µM CHIR99021 was added to the existing media in each well to reach a final concentration of 12 µM”. Concentrations of CHIR99021 as high as 36 µM can cause cytotoxic effects in cells, thus claim 8 is being interpreted to be met by any concentration of CHIR99021 in the art for the sake of compact prosecution.
Regarding claim 1, Thon teaches a method of differentiating pluripotent stem cells into endothelial cells comprising the steps of (i) culturing pluripotent stem cells on collagen IV-coated surface in a base culture medium comprising a ROCK Inhibitor ([0172]/[0173]). Thon teaches contacting the cells with a GSK3 inhibitor but does not specify that this must occur as a standalone step (ii) as claimed. Thon teaches step (iii) of culturing the cells on the collagen IV-coated surface in a culture medium containing FGF2, VEGF, and BMP4, for a total of 2-6 days ([0175]). Thon teaches that after 6-48 hours of BMP4 culture, the BMP4 content is dispensable and not required, amounting to step (iv) culturing the cells in a base medium containing FGF2 and VEGF, and which does not contain BMP4 also included in the 2-6 days described by Thon ([0175]). Thon teaches step (v) by teaching that differentiation can be assessed by the expression of markers, specifically CD144, and that the endothelial cells produced express CD144, further that detectable magnetic labels can be employed ([0176]/[0113]).
Regarding claim 4, Thon teaches that the ROCK inhibitor is Y-27632 ([0172]).
Regarding claim 6, Thon teaches that step (i) is about 1 day or 24 hours ([0172]).
Regarding claim 7, Thon teaches that a GSK3 inhibitor, CHIR99021, is employed ([0175]).
Regarding claim 8, Thon teaches a concentration of 6 µM of CHIR99021 ([0287]).
Regarding claim 9, Although Thon teaches the employment of the GSK3 inhibitor of step (ii) in a combination with other steps, Thon specifically teaches that the GSK3 inhibitor be included for only the first 48 hours of differentiation which meets the limitation of about 1 day ([0287]).
Regarding claim 10, Thon teaches that the FGF2 is present at about 50 µg/ml ([0175]).
Regarding claim 11, Thon teaches that the VEGF is present at about 50 µg/ml ([0175]).
Regarding claim 12, Thon teaches that the BMP4 is present at about 50 µg/ml ([0175]).
Regarding claim 13, Thon teaches that the cells can be passaged between steps (iii) and (iv) because Thon teaches passaging the cells at every 3 or 4 days and step (iii) is a 2-6 day incubation so based on the teachings of Thon one would passage the cells between steps (iii) and (iv) ([0167]).
Regarding claim 20, Thon teaches that steps (i) and the step of incubating with a GSK3 inhibitor which is not a fully separate step (ii) are cultured under hypoxic conditions ([0191]).
Regarding claim 21, Thon teaches that the pluripotent cells can be embryonic stem cells, embryo-derived stem cells, or induced pluripotent stem cells ([0129]).
Thon does not explicitly teach that step (ii) of contacting the cells on the collagen-IV coated surface with a GSK3 inhibitor is a distinct step (ii) as required by claim 1. Thon does not explicitly teach that the cells having CD144 expression are separated to form the population of endothelial cells as require by claim 1. Thon does not teach the additional step of culturing the cells of step (v) having expression of CD144 in a base culture medium comprising a TFGb inhibitor as required by claim 2. Thon does not teach that the concentration of the ROCK inhibitor Y-27632 is about 10 µM as required by claim 5. Thon does not teach that the culturing of step (vi) is about 6 days. Thon does not teach that the separating in (v) is conducted using immunomagnetic cell separation as required by claim 19.
However, Gerecht teaches a similar differentiation procedure to that of Thon. Gerecht teaches a method of generating early endothelial cells through contacting pluripotent stem cells with a ROCK inhibitor, Y-27632, and subsequently contacting the cells with the GSK3 inhibitor, CHIR99021; all of which is performed on collagen IV-coated surfaces (fig. 1; claim 1, 3, and 5).
Regarding claim 1, Gerecht teaches a step (i) of contacting pluripotent stem cells with a ROCK inhibitor, Y-27632 (see claim 3; Fig. 1). Gerecht teaches step (ii) of contacting the cells of step (i) with a GSK3 inhibitor, CHIR99021 (see claim 3). Gerecht teaches step (v) of separating the cells expressing CD144, also known as VE-Cadherin, to obtain endothelial cells ([0036]).
Regarding claims 2 and 17, Gerecht teaches that after differentiation, the endothelial cells were sorted based on VEcad+ expression and that the sorted cells were subcultured and expanded for another 6 days ([0036]). Gerecht teaches in the differentiation protocol that differentiated cells were collected and plated in endothelial growth media supplemented with SB431542, a TGFb inhibitor, for an additional 6 days. The description of the differentiated cells being sorted and further cultured for 6 days of [0036] aligns with the differentiation procedure outlined in [0095] and thus Gerecht teaches the limitation of claims 2 and 17.
Regarding claim 5, Gerecht teaches that the Rock inhibitor, Y-27632, is present at a concentration of 10 µM ([0087]).
Regarding claim 19, Gerecht teaches that the separation is done through magnetic cell sorting ([0036]).
Regarding claim 22, Thon and Gerecht renders the claimed endothelial cells made by the method of claim 1 obvious based on the combination of Thon and Gerecht teaching the method of claim 1.
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the differentiation method taught by Thon with the similar differentiation method taught by Gerecht to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Gerecht teaches that their method differentiates T1D-hiPSCs into EVCs, maturation into functional ECs, and generation of vascular networks in a deliverable hydrogel and as a response to hypoxia ([0004]). One of ordinary skill in the art would have a reasonable expectation of success when combining Thon with Gerecht because both Thon and Gerecht teach similar methods employing overlapping steps and cell treatments to arrive at endothelial cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
Prosecution Insights