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 of Group I (claims 1, 2, 5, 12, 17, 42, 45, 47, 54, 59 and 70) in the reply filed on March 9, 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)).
Claims 60, 63, 67, 71, 73, 75, and 78-80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US21/31123, filed May 6, 2021. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/021,929, filed May 8, 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. The earliest possible priority date is May 8, 2020.
Information Disclosure Statement
The information disclosure statements filed June 22, 2023 and Jan. 6, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Claim Rejections - 35 USC § 101
Claims 1, 2, 5, 12, 17, 42, 45, 47, 54, 59 and 70 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more. The claim(s) recite(s) a population of isolated cells including at least 70% human amniotic epithelial cells (hAECs) with no more than 2% hematopoietic cells within the population and the non-hematopoietic cells are 99% HLA-DR+ and a pharmaceutically acceptable excipient. Both the cells and the pharmaceutical excipient are not different from naturally occurring counterparts. The cells are multipotent cells obtained from amniotic membranes of a human placenta, which have been isolated (removed) from tissue and physically separated from other cell types, which usually results in an increase in the amount (%) of hAECs. (specification, pg. 13-14, “Human amniotic epithelial cells (hAECs)). Although the cells are recited as being isolated and are in
This judicial exception is not integrated into a practical application because the recited cells (hAECs), even though recited as being isolated are not markedly different than their naturally occurring counterpart. Even though the claimed population enrichment likely does not occur in nature, this is not enough to distinguish the claimed cell population from its naturally occurring counterpart. The Supreme Court in Funk Bros. Seed Co. v. Kalo Inoculant Co.. 333 U.S. 127, 131 (1948) held that even though the combination of bacteria did not occur in nature, the combination [of bacteria] did not provide a different structural or functional characteristic than each bacteria possessed on its own.
"It is no more than the discovery of some of the handiwork of nature and hence is not patentable. The aggregation of select strains of the several species into one product is an application of that newly-discovered natural principle....Each species has the same effect it always had. The bacteria perform in their natural way.” Id. In the instant situation if "bacteria" is replaced with “hAECs,” the same reasoning applies. In concentrating the claimed cell population, applicants have not improved their natural functioning; rather, they are seeking to produce a product that has therapeutic value precisely because each cells functions as closely as possible to its naturally occurring counterpart.
In the aggregate of cells, each cell functions the same as it would when not aggregated – each cells’ function (and structure) is the same in the aggregate as it is singly. As such, the aggregation is analogous to the naturally-occurring bacterial group in Funk Bros., which the Supreme Court found to be patent ineligible subject matter.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims include only the recited cells and a pharmaceutical excipient. The pharmaceutical excipient is broadly defined, and includes saline, more specifically, physiological saline (0.9% w/v NaCl, pH 5.4). (pg. 17 “Pharmaceutical Excipients”). Physiological saline is intended to mimic physiological solutions – it’s salinity mirrors that of the natural mileau that cells find themselves in. Neither the hAECs on their own, the pharmaceutical excipient on its own or the combination of cells and the pharmaceutical excipient would amount to significantly more than the naturally occurring product, as the excipient is intended to maintain the hAECs, replicating the state that they find while in the human body.
Dependent claims 2, 5, 12 17, 42, 45, 47, 54, 59 and 70 do not add additionally elements that change this analysis, as they further characterize the cells (capable of adhering to an ECM protein; express claimed surface biomarkers; density of cells; the excipient is physiological saline), as such, they are subject matter ineligible for the same reasons explained above.
Claim Rejections - 35 USC § 102
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.
(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) 42, 47 and 59 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vosdoganes et al. (American J Obstetrics & Gynecology, 2011).
The claims are directed to a composition that includes hAECs and a pharmaceutically acceptable excipient.
Vosdoganes et al. teaches a population of isolated hAECs, which results in less than 1% of cells expressing CD105 (stromal cell biomarker) and 94% of the cells expressing EpCam-positive (94% of cells are hAECs). (pg. 156e26, 1st col). The cells are suspended in sterile saline (“Before injection, first passage hAECs were labeled passively with carbxyfluorescein succinimidyl ester (CFSE) and resuspended in sterile saline solution…) (“a pharmaceutically acceptable excipient”). (pg. 156e26, 1st col).
With respect to claim 42, Vosdoganes et al. teaches 94% (above 90%) of cells are hAECs and that less than 2% of the cells express a stromal cell marker. (pg. 156e26, 1st col).
With respect to claim 47, Vosdoganes et al. teaches 94% (above 90%) of cells express epCAM. (pg. 156e26, 1st col).
With respect to claim 59, Vosdoganes et al. teaches the cells are removed from the amnion, isolated, and then passaged once (“first passage hAECs”) (pg. 156e26, 1st col), inherently teaching that less than 0.1% DMSO is present, as no DMSO has been used in the process.
Claim Rejections - 35 USC § 102 / § 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.
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, 2, 5, 12, 17, 45, 54, and 70 are rejected as being anticipated by 35 U.S.C. 102, or in the alternative, as being obvious over 35 U.S.C. 103 as being unpatentable over Vosdoganes et al. (American J Obstetrics & Gynecology, 2011, cited in the IDS filed on June 22, 2023) as applied to claims 42, 47 and 59 above.
The claims are directed to compositions including a population of isolated human amniotic epithelial cells (hAECs) that meet certain “purity” standards (have a certain percentage of hAECs, have less than a certain amount of unwanted cells (hematopoietic cells or stromal cells) and most of the cells express commonly known epithelial cell biomarkers (e.g. “less than 1% of the non-hematopoietic cell are negative for HLA-DR”, in other words, 99% of the remaining cells express the epithelial cell biomarker HLA-DR). The composition includes hAECs and a pharmaceutically acceptable excipient.
Claim 1 recites less than 2% of the cell population is hematopoietic cells (Vosdoganes et al. teaches a population of isolated hAECs, which results in 1% of cells expressing CD45 (a hematopoietic cell biomarker); that at least 70% of the isolated cells are hAECs (Vosdoganes et al. teaches 94% of cells are hAECs. (pg. 156e26, 1st col).
With respect to claim 3, Vosdognes et al. teach that the hAECs express epCAM. (pg. 156e26, 1st col).
With respect to claim 59, teaches the cells are removed from the amnion, isolated, and then passaged once (“first passage hAECs”) (pg. 156e26, 1st col), inherently teaching that less than 0.1% DMSO is present, as no DMSO has been used in the process.
Vosdoganes et al. does not explicitly teach that 99% of the hAECs are positive for HLA-DR (“less than 1% of the remaining cells are negative for HLA-DR”). (claim 1) Vosdoganes et al. does not explicitly teach that the cells are capable of adhereing to the claimed ECM proteins (claim 2). Vosdoganes et al. does not teach that less than 1% of cells express a hematopoietic cell marker, but rather teaches that 1% of cells express CD105, a hematopoietic cell marker.
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' hAECs differs, and if so to what extent, from the hAECs taught by Vosdoganes et al. Accordingly, it has been established that the prior art hAECs, which is identified as the same cell type, was isolated from the same tissue and has been quantified by some of the same biomarkers in the claimed invention, demonstrates a reasonable probability that it is either identical or sufficiently similar to the claimed hAECs that whatever differences exist are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants.
Merely because a characteristic of a hAECs is not disclosed in a reference does not make use of the known hAECs patentable. The claimed hAECs possesses inherent characteristics which might not be displayed in the tests used the reference. Clear evidence that the hAECs of the cited prior art does not possess a critical characteristic that is possessed by the claimed hAECs, would advance prosecution and might permit allowance of claims to applicants' use of the claimed hAECs.
Even if Vosdoganes et al.' s hAECs does not possess the claimed functionality, it would have been obvious to have further purified the cells to get to a population that conforms with the purity specified in the various claim limitations, as Vosdoganes et al. explicitly teach FACs detection of their cells. pg. 156e26, 2nd col), FACs detection would enable one of ordinary skill in the art to check for the claimed biomarkers and to have further purified the cells to the claimed parameters, as Vosdoganes et al. teach that having a purified, isolated population of Vosdoganes et al. is desired (as established by the purity that they do teach). As Vosdoganes et al. teaches that the cells were 94% + for epCAM (another hAECs biomarker), it is expected that if the cells were tested for HLA-DR, they would also be 94% + for it.
With respect to claims 12, 54 and 70, these claims are as they recite the product obtained using the process specified. "[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) (citations omitted) (emphasis added). MPEP 2113.
As such, it is asserted that these product-by-process claims are also either inherently taught or rendered obvious by by Vosdoganes et al, as any differences that are present are not patentably distinct as by Vosdoganes et al. teaches isolation and purification of the same cell type.
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/Primary Examiner, Art Unit 1634