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, 9-11, 16, 20, 22, 24, 29-30, and 68-72 in the reply filed on 12/22/2025 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)).
All non-elected claims have been cancelled by Applicant, in the reply filed on 12/22/2025.
Status of the Claims
Claims 1-2, 5, 9-11, 16, 20, 22, 24, 29-30, and 68-73 are currently pending.
Claims 1, 2, 10, 20, and 24 are amended.
Claims 3-4, 6-8, 12-15, 17-19, 21, 23, 25-28, and 31-67 are cancelled.
New claims 68-73 have been added.
Claims 1-2, 5, 9-11, 16, 20, 22, 24, 29-30, and 68-73 have been considered on the merits.
Claim Objections
Claim 9 is objected to because of the following informalities: line 2 contains the acronym “HEC”, which is defined in the last line of claim 9. The first instance of using the term should read “hemogenic endothelial cells (HECs)” and all subsequent recitations should be amended to “HEC”. Appropriate correction is required.
Claim 20 is objected to because of the following informalities: the phrase “a notch agonist to obtain CD34+CD45+,” in line 3 should be amended to “a notch agonist to obtain CD34+CD45+ hematopoietic progenitor cells”. Appropriate correction is required.
Specification
The use of the terms Knockout™ serum replacement in at least [0294], StemPro-34™ media in at least [0295], TrypLE™ in at least [0295], and Matrigel™ in at least [0297], which are trade names or a marks used in commerce, has been noted in this application. 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 § 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 22, 24, 30, 72, and 73 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.
Claim 22 requires that “the method further comprises contacting the CD34+CD45+ hematopoietic progenitor cells or the expanded CD34+CD45+ hematopoietic progenitor cells to obtain multipotent lineage cells”, which is indefinite. It is unclear what the cells must be contacted with to obtain multipotent lineage cells. Appropriate clarification is required.
Claims 24 and 72 depends from claim 22 which requires that CD34+CD45+ hematopoietic progenitor cells are contacted to obtain multipotent lineage cells, which is indefinite. Regarding claim 24, the claim limitations limit the “multipotent lineage cells” to be macrophage cells, mast cells, erythrocytes, granulocytes, or T lymphocytes. Of these cell types, only certain subsets of T lymphocytes, T memory stem cells, are considered multipotent cells. Therefore, it is unclear how the “multipotent lineage cells” can be unipotent terminally differentiated cells such as macrophage cells, mast cells, erythrocytes, granulocytes, or non-memory T lymphocytes. Regarding claim 72, the claim further limits wherein the T lymphocytes are gamma/delta, alpha/beta, and/or Vdelta2 T lymphocytes. All of these subsets of T lymphocytes are not regarded as multipotent cells and therefore render the claim indefinite. Appropriate clarification is required.
Claim 30 recites the limitation "isolated cells" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 73 recites the limitation “the ratio of BMP4 to FGF2 to Activin A is about 10:5:6 or about 10:5:2 or within about 10:5:6 to about 10:5:2” in lines 3-4, which is indefinite. The ratio is not clearly defined by the recitation of “within about”. The term “within” implies that the ratio must fall in between 10:5:6 and 10:5:2, however the term “about” allows for a ratio which falls on either side of the claimed range. Therefore, it is unclear what the metes and bounds of the term “within about” are. Appropriate clarification is required.
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 1-2, 5, 9-11, 16, 20, 22, 24, 29, 30, and 69-73 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sturgeon et al (Nat Biotechnol. 2014), as evidenced by BD Biosciences (BD Pharmingen™ APC Mouse anti-human CD235a/b, “Antibody Details”, accessed 01/20/2026).
Regarding claim 1, Sturgeon teaches a method of producing KDR+CD235a+ mesoderm cells through the steps of contacting pluripotent stem cells (PSCs) with a PSC culture composition comprising BMP4, a BMP receptor agonist, and then contacting the resulting population of cells with a mesoderm specifying culture composition comprising BMP4, FGF2 (also known as bFGF), and Activin A to produce KDR+CD235a+ mesoderm cells as required by claims 1, 5, and 16 (pg. 10, para 3). Sturgeon teaches that the ratio between BMP4, FGF2, and Activin A is 10:5:6 ng/ml respectively as required by claim 73 (pg. 10, para 3). Sturgeon teaches that the PSCs are contacted with the mesoderm specifying culture composition for about 3 days as required by claim 2 (pg. 10, para 3). Sturgeon teaches that the PSCs are either human ESC or human induced PSCs and that they are used to form embryoid bodies during the method as required by claims 2 and 69 (pg. 10, para 3). Sturgeon teaches that the method further comprises contacting the KDR+CD235a+ mesoderm cells with an HEC culture media comprising VEGF and the hematopoietic cytokines IL-6, IL-11, SCF, EPO, IGF-1, and Flt-3L to obtain CD34+KDR+ hemogenic endothelial cells (HECs) as required by claim 9 (pg. 10, para 3 and 5). Sturgeon also teaches that the method further comprises culturing the CD34+KDR+ HECs to obtain CD34+CD43- HECs or to obtain CD43+ hematopoietic progenitor cells as required by claim 10 (pg. 10, para 3 and 6 and pg. 3, para 3). Sturgeon teaches that all KDR+ cells that gave rise to CD34+ cells did so within a day of culture as required by claim 70 (pg. 3, para 3). The method further comprises culturing the CD43+ hematopoietic progenitor cells to obtain primitive program lineage cells as required by claim 11 (pg. 7, para 2; Fig. 5). Sturgeon teaches wherein the method further comprises contacting the CD34+CD43- HECs with a notch agonist to obtain CD34+CD45+ cells as required by claim 20 (pg. 5, para 1; pg. 8, para 1; and Fig. 2A, 2D, and 2E). Sturgeon teaches that the notch agonist is a notch ligand as required by claim 29 (pg. 8, para 1). Sturgeon teaches that the method comprises contacting the CD43+CD45+ hematopoietic progenitor cells to obtain multipotent lineage cells and those cells are isolated and are taught to be erythroid colonies as required by claims 22 and 24 (Fig. 5; pg. 4, para 2). Sturgeon teaches that the isolated cells are resuspended in a composition that comprises a gel, in this case Matrigel™, and that the composition comprises an additional cell type, in this case mouse embryonic fibroblasts, as required by claim 30 (pg. 10, para 3). Sturgeon teaches that the CD34+CD45+ cells comprise CD34+CD45+CD7+ cells as required by claim 71 (Fig. 2). Sturgeon teaches that the resultant progenitor cells are able to further differentiate into cells with T-lymphoid potential, i.e. ability to differentiate into any T-lymphoid cell type, as required by claim 72 (Fig. 5).
Sturgeon meets the limitations of claim 1 wherein the mesoderm cells that are produced are positive for the expression of both CD235a and CD235b as evidenced by BD Biosciences. Sturgeon teaches the use of the “CD235a-APC (clone HIR2)” antibody for Flow cytometry and cell sorting (pg. 10, para 4). BD Biosciences discloses that the HIR2 clone of the CD235 antibody binds both CD235a and CD235b (pg. 2, para 1). Therefore, Sturgeon meets the limitation of the cells being both CD235a and CD235b positive.
Claim 71 contains a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. The result recited is wherein the CD34+CD45+ cells comprise CD34+CD45+CD90-CD7+ cells, and Sturgeon is silent as to the expression of CD90 on the resultant cells. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on the method of claim 20 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, Sturgeon anticipates the claims.
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.
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.
Claims 1, 16, and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Sturgeon et al (Nat Biotechnol. 2014) as evidenced by BD Biosciences (BD Pharmingen™ APC Mouse anti-human CD235a/b, “Antibody Details”, accessed 01/20/2026), in view of Watanabe et al (Nature Biotechnology, 2007).
With regards to claim 68, Sturgeon teaches the limitation of the independent claim 1 above.
Sturgeon does not teach that the pluripotent stem cell culture composition comprises a ROCK inhibitor as required by claim 68. Sturgeon does meet the required limitations of claim 16, however Sturgeon does not teach the optional limitation of the ROCK inhibitor being Y-27632.
However, Watanabe teaches about the effects of the use of a ROCK inhibitor on the survival of embryonic stem cells (abstract). Watanabe teaches that “we examined the effects of several caspase inhibitors, growth factors, trophic factors and kinase inhibitors. Of the compounds tested, Y-27632, a selective inhibitor of p160-Rhoassociated coiled-coil kinase (ROCK)2,19, was the most potent inhibitor of apoptosis.” (pg. 681, col. 1, para 2). Additionally, Watanabe teaches that “[a]fter five low-density passages, Y-27632-treated hES cells retained the competence to differentiate into neural cells (see below), mesodermal cells and endodermal precursors in vitro (Fig. 1g–k)” as required by claims 16 and 68 (pg. 681, col. 2, para 3).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of producing KDR+CD235a/b mesoderm cells taught by Sturgeon with the ROCK inhibitor within the pluripotent stem cell media taught by Watanabe to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Watanabe teaches that “we examined the effects of several caspase inhibitors, growth factors, trophic factors and kinase inhibitors. Of the compounds tested, Y-27632, a selective inhibitor of p160-Rhoassociated coiled-coil kinase (ROCK)2,19, was the most potent inhibitor of apoptosis.” (pg. 681, col. 1, para 2). One of ordinary skill in the art would have a reasonable expectation of success when combining Sturgeon with Watanabe because Watanabe teaches that the cells cultured with the ROCK inhibitor are able to successfully differentiate into mesodermal cells in vitro (pg. 681, col. 2, para 3).
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.
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.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/DAVID A MONTANARI/Examiner, Art Unit 1632