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 .
The preliminary amendments dated 5/21/2024 are acknowledged and under consideration in this office action. Claims 42-46 and 49-55 are under consideration in this office action.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 recites the abbreviations “BM” and “HSCs” without first spelling out the full term. Amending these first recitations of the abbreviation to state “bone marrow (BM)” and “hematopoietic stem cells (HSCs)” will be remedial. Appropriate correction is required.
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 45-46 and 50-52 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.
Regarding claim 45, the term “aged HSC” in claim 45 is a relative term which renders the claim indefinite. The term “aged HSC” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification does not provide a specific definition for an “aged HSC” and the degree of being considered an “age HSC” will be dependent upon the species origin and will vary depending on the parameters one would consider to be a measure of “aged” in an HSC. The specification does not define which parameters are deemed “aged” and which species this may be considered “aged”. As such, the metes and bound of “aged HSC” are not apparent.
Claim 46 recites, “A hematopoietic stem cell population produced by the method of claim 42”. Claim 42 recites, “A method of preparing an endothelial cell vascular niche effective for maintain functional HSCs”, further the method has the steps of “providing a hematopoietic cell population; contacting the hematopoietic cell population with BM endothelial cells; and incubating the hematopoietic cell population and BM endothelial cells for a period of time to produce a mixed hematopoietic cell/BM endothelial cell population”. A such, the method does not appear to produce HSC, given that the body of the claims do not require HSCs and only require “to produce a mixed hematopoietic cell/BM endothelial cell population” and the preamble recites “preparing an endothelial vascular niche” with the intended use of “effective for maintaining functional HSCs”. As such, the relationship between the method cited as producing the claimed hematopoietic stem cell population and the actual hematopoietic stem cell population product are not clearly delineated. (In other words, how does the method that does not produce or require HSCs produce them?). For purposes of interpretation, claim 46 is being interpreted as hematopoietic stem cell population prepared by any means.
Regarding claims 50-52, claim 50 recites, “the BM endothelial cells (BMECS) are derived from a young individual, wherein the young individual is 35 years of age or less”. Claim 51 recites, ““the BM endothelial cells (BMECS) are derived from a young individual, wherein the young individual is 30 years of age or less”. Claim 52 recites, ““the BM endothelial cells (BMECS) are derived from a young individual, wherein the young individual is 25 years of age or less”. “A young individual” is a term is different depending on the species of animal. 35, 30, and 25 years of age or less appears to be specifying that the species from which the cell is being derived is human. The specification also describes these ages as they pertain to humans. However, base claim 42, to which claims 50-52 refer, does not specify the species of the BM endothelial cell. As such, intended scope of claims 50-52 is not apparent because it is not apparent if the scope is intended to be limited to human BM endothelial cells because young would be considered 35, 30, and 25 years or less or if the claimed BM endothelial cells are intended to broadly encompass any species as recited in the base claim. Claim 53 depends upon claim 50 and therefore also has this issue of indefiniteness by dependency.
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 46 is rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more.
The claim(s) recite(s) “a population of isolated expanded potential stem cells”. According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories of invention (i.e. process, machine, manufacture, or composition of matter). Claim 46 is drawn to a composition of matter comprising cells. Thus claim 46 meets the requirements for step 1 of the analysis.
Second, the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019PEG, “directed to” is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application”, requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application).
Regarding the first prong (1), claim 46 is product claims reciting “a hematopoietic stem cell population”. Morrison and Scadden (Nature 505:327-334) report, Hematopoietic stem cell (HSC) niches are present in diverse tissues throughout development, beginning in the aorta–gonad mesonephros (AGM) region and the yolk sac, followed by the placenta, fetal liver, spleen and bone marrow.” See p. 327, col 1, paragraph 1. Thus, claim 46 is directed to a hematopoietic stem cell population which is a product of nature, as evidence by Morrison and Scadden, and thus the claim is directed to a judicial exception.
Regarding the second prong (2), claim 46 recites the additional elements “produce by the method of claim 42”. A process of making the claimed HSC population does not constitute integrating the judicial exception into a practical application. Thus, claim 46 meets the requirement of step 2A as being directed to a judicial exception.
Third, if a judicial exception is present in the claim, it is further assessed to determine if the claim recites any additional elements or steps that are sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. As discussed above, the only additional element is process of making the claimed HSC population. This method does not impart any marked distinction and is suggestive of an HSC that functions more effectively like the natural product. As such, the HSC of claim 42 is indistinguishable from the HSC found in nature. As such, claim 46 does not meet the requirements of step 2B.
In conclusion, claim 46 does meet all the requirements of the 2019PEG and therefore deemed patent ineligible because the claim recites a judicial exception that is neither integrated into a practical application markedly different from the HSC population product of nature.
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.
(1) Claim(s) 46 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Morrison and Scadden (Nature 505:327-334, 2014).
Morrison and Scadden discloses hematopoietic stem cell (HSC) niches are present in diverse tissues throughout development, beginning in the aorta–gonad mesonephros (AGM) region and the yolk sac, followed by the placenta, fetal liver, spleen and bone marrow. See p. 327, col 1, paragraph 1. HSC niches comprise a population of HSCs. Thus, Morrison and Scadden expressly discloses the limitations of claim 46.
(2) Claim(s) 42 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Asch (WO 96/00779 pub date:6/26/1995; effectively filed 6/28/1994).
Regarding claim 42, Asch discloses hematopoietic progenitor cells may be obtained from human mononuclear cells produced by bone marrow and peripheral blood (p. 16, lines 14-30). Thus, Asch discloses “providing a hematopoietic cell population”, as recited in the first step of claim 42. Asch discloses Ex vivo use of bone marrow endothelial cells or cytokines therefrom is by direct addition to culture of hematopoietic progenitor cells in physiological buffer or culture medium (p. 16, lines 31-35). These disclosures expressly discloses the limitations “contacting the hematopoietic cell population with BM endothelial cells” of the second step of claim 42. These disclosure also disclose the third set of “incubating the hematopoietic stem cell population and BM endothelial cells for a period of time to obtain a mixed hematopoietic cell/ BM endothelial cell population” because the claims does not specify any specific period of time and all that is requires is “a mixed hematopoietic cell/ BM endothelial cell population”. As such, the exact moment that BM endothelial cells are directly added to the hematopoietic progenitor cells in Asch “a mixed hematopoietic cell/ BM endothelial cell population” is obtained. Further, since all of the steps of Asch are expressly disclose the end result “a mixed hematopoietic cell/ BM endothelial cell population”, Asch also expressly discloses “a method of preparing an endothelial cell vascular niche” as recited in the preamble of claim 42. The preamble further recites the intended use of the prepared endothelial cell vascular niche as “effective for maintaining functional HSCs”. The intended use does not further impart any steps or elements into the body of the method expressly disclosed by Asch. As such, the intended use does not further limit claim 42 and the above-described disclosures meet the requisite limitations of claim 42. Claim 42 also has a “wherein” clause that further describes the function HSC that are recited by in the preamble’s disclosed intended use. Again, the intended use does not further limit claim 42 and the above-described disclosures meet the requisite limitations of claim 42.
Regarding claim 43, this claim also specifies limitations of the HSCs which is a part of the recited intended use. The intended use does not further limit the claimed method and thus Asch expressly discloses all the required limitations of claim 43. Even further, the Asch discloses that the hematopoietic progenitor cells can be bone marrow CD34+ progenitor cells (p. 17, last paragraph). That can be separated from bone marrow (p. 16, lines 14-25). Thus, Asch expressly discloses the limitations of claim 43 as well.
Regarding claim 44, this claim further specifies limitations of the HSCs of the intended use of the preamble and thus is not further limiting for reasons discussed above. As such, Asch discloses the requisite limitations of this claim as discussed above. Further Asch discloses that the cells can be derived from bone marrow or peripheral blood as discussed above. Thus Asch expressly discloses the limitations.
Regarding claim 45, this claim further specifies limitations of the HSCs of the intended use of the preamble and thus is not further limiting for reasons discussed above. As such, Asch discloses the requisite limitations of this claim as discussed above.
Regarding claim 46, Asch discloses the claims hematopoietic stem cell population present in the method of claim 42 as discussed above.
Regarding claim 49, this claim further specifies limitations of the HSCs of the intended use of the preamble and thus is not further limiting for reasons discussed above. As such, Asch discloses the requisite limitations of this claim as discussed above. Further Asch discloses the population is CD34+ derived from bone marrow. As such, the population would have at least one CD34+ cell, HSC, and HPC as claimed.
Regarding claim 54, Asch discloses that the BM endothelial cells are derived from bone marrow as discussed above.
Regarding claim 55, Asch discloses that the hematopoietic progenitor cell/BM endothelial cell mixture can be in a minimum essential medium supplemented with antibiotics (i.e. a therapeutic agent) paragraph bridging (pp.6-17). As such, Asch expressly discloses the limitations of claim 55.
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.
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) 42-46 and 49-53 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Poulos (Poulos et al. 2015 5(5):881-894; of record in IDS).
Regarding claim 42, the claim is being interpreted as describe in the above rejection. Poulos discloses to examine the capacity of our BMEC-Akt1 and BMS-Akt1 cells to support HSCs, we developed an ex vivo co-culture system in which CD45+lineage cKIT+SCA1+ (LKS) HSPCs were cultured on a feeder layer of BMEC-Akt1 or BMS Akt1 cells under serum-free conditions. See p. 882, col 2, last paragraph. These disclosures expressly disclose the providing, contacting, and incubating steps of the claim. They also disclose end result of producing the claimed mixed hematopoietic/BM endothelial cell population and therefore also discloses a method of preparing an endothelial cell vascular niche effective for maintaining functional HSC. Poulos further discloses that the BMEC-Akt1 acts as an ex vivo pro-HSC niche that provides the appropriate combination and levels of angiocrine factors that regulate the maintenance ofHSCs, retaining their ability to repopulate lethally irradiated recipients, leading to long-term, multilineage engraftment (p. 884, col 2). Thus Poulos expressly discloses all of the limitations of claim 42.
Regarding claim 43, Poulos discloses that the HSPC were sorted to purity (p. 882 col 2, last paragraph). Thus Poulos expressly discloses the limitations of claim 43.
Regarding claim 44, Poulos is silent as to the origin of the HSCs and HSPC. However, Poulos discloses that the cells expressing HSC/HSPC marker (p. 884, col 2). As such, inherently these cells had to be derived from bone marrow, mobilized peripheral blood, placenta, or cord blood.
Regarding claim 45, as discussed above this claim specifies that HSC which is not further limiting to the claimed method being it is part of the intended use. As such, the disclosures by Poulos discussed above disclose the limitations of claim 45.
Regarding claim 46, Poulos discloses an HSC population as discussed above.
Regarding claim 49, Poulos is silent as to whether the HSC/HSPC are CD34+. However, as discussed above, this claims further limits characteristics of the cells of the intended use and therefore does not further structurally/functionally limit the base claim. As such, Poulos’s disclosure discussed above discloses the requisite limitations of the claims.
Regarding claims 50-52, Poulos discloses that the BMEC were immunopurified using CD31-captured magnetic beads from adult (12 weeks) mice (p. 892, col 1, ‘BM Endothelial and Stromal Cell Culture”). As such, the BMEC were from young individuals as being defined by the claims as 35 years old or less (claim 50), 30 years old or less (claim 51), and 25 years old or less.
Regarding claim 53, Poulos discloses that the BMECs were CD31+ (p. 892, col 1, ‘BM Endothelial and Stromal Cell Culture”) and VECAD+ (figure 1, p. 883). Poulos further discloses that the BMECs were depleted of hematopoietic lineage (p. 882, col 1), which means they are CD45-. Poulos further discloses we confirmed that the BM vasculature is composed of two distinct VECAD+ EC populations, including SCA1+VEGFR3 arteriole and SCA1VEGFR3+ sinusoid ECs. To test whether the endothelial and perivascular components of the BM vascular niche support adult HSCs ex vivo, we sought to establish highly pure and robust BMEC. Resulting cultures expressed genes characteristic of endothelial and stromal cells (Figures S1A and
S1B). To confirm the identity of our BMEC-Akt1 cultures, we analyzed the expression of pan EC (VECAD), arteriole EC (SCA1), and sinusoidal EC (VEGFR3) markers
. BM-derived ECs displayed a phenotypic arteriole identity, staining for SCA1, but not VEGFR3 (Figure 1B). Poulos further describe phenotypic and functional assess used to demonstrate that there BMEC population was in fact BMEC. See page 882. Poulos is silent as to the expression of Lin, CD45, and TER119. However, as discussed above Poulos provides sufficient evidence that the cells are in fact BMEC cells. Further, Lin and CD45 are well established hematopoietic lineage markers and TER119 is well established erythroid cell marker. Given Poulos provide adequate evidence to demonstrate that the BMEC cells are characteristic BMEC cells, one or ordinary skill would also reasonable expect that these cells are inherently CD45-, Lin-, and TER119-, absent evidence to the contrary.
Regarding claim 54, Poulos discloses BMEC were isolated from bone marrow (p. 882, col 1). Poulos also discloses a co-culture of HSC human EC from umbilical vein (p. 881, col 2, last paragraph).
Regarding claim 55, the claim further specifies that the hematopoietic cell/BM endothelial cell population is treated with an additional therapeutic agent. The breadth of “an additional therapeutic agent” encompasses any agent that supports or benefits the cell mixture, including placing them in a supportive media. Poulos discloses that the co-cultures were supplemented with StemSpan SFEM and sKITL every 2 days (p. 892, “Ex Vivo Hematopoietic Co-Cultures” section).
In conclusion, the prior art of Poulos anticipates the claims because it expressly or inherently discloses all the requisite limitations of the claims.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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