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 .
Detailed Action
This action is in response to the papers filed September 2, 2026.
Notice of Non-responsive Amendment
Applicant’s reply filed on 09/02/2026 is not fully responsive to the previous Office action because of the following omission(s) or matter(s):
Applicant’s amendment to the claims does not comply with one or more of the requirements of 37 CFR 1.121(c). In this case, the amendment to claim 1 indicates both addition by underlining and deletion by strike-through of the phrase “a β2M” in the second to last line of the claim. While it would be proper to reject entry of the present amendment for noncompliance, it is instead respectfully offered as a reminder that Applicant must comply with the requirements of 37 CFR 1.121(c) when making amendments to the claims in order to avoid the issuance of a Notice of Non-responsive Amendment which would delay prosecution and potentially have an adverse effect on any patent term adjustment should the claims proceed to issue. For examination purposes in this action, the phrase “a β2M” will be treated as deleted.
Claim Amendments
Applicant’s amendment to the claims filed 09/02/2026 is acknowledged.
Claims 8-16, 19-27, 29 and 37 have been cancelled.
Claims 1-2, 18, 28 and 31 are amended.
Claim 38 is newly added.
Claims 1-7, 17-18, 28, 30-36 and 38 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/30/2026 has been considered.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See, the Requirement for Restriction/Election mailed 09/17/2025.
Applicant elected without traverse the invention of Group 1, drawn to a method of producing megakaryocytes and/or platelets, in the reply filed 12/16/2025.
Priority
The instant application 18/248,193 was filed on 04/06/2023. This application is a national stage of international application PCT/US2021/071903 filed 10/15/2021, claiming priority based on U.S. Provisional Application No. 63/092,024 filed 10/15/2020.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 09/02/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
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.
Claim 32 is 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.
This rejection is newly applied, necessitated by amendment.
Claim 32 recites the limitation "the suitable conditions of step (b)". There is insufficient antecedent basis for this limitation in the claim. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 32 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
This rejection is newly applied, necessitated by amendment.
Claim 32, dependent upon claim 31, recites that step (b) comprises an effective amount of one or more ROCK inhibitors in the media. However, claim 31 already recites this limitation. Therefore, claim 32 is in improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim 36 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rebulla et al. (2017) “Clinical effectiveness of platelets in additive solution treated with two commercial pathogen‐reduction technologies” Transfusion, 57(5), 1171-1183.
This rejection is newly applied, necessitated by amendment.
Rebulla teaches treatment of patients with hematological cancer by platelet transfusions. See, pages 1171-1173.
Rebulla does not teach that the platelets are “produced by the method of claim 2,” as instantly claimed in claim 36.
The limitation “produced by the method of claim 2” is a product-by-process limitation of the platelets used in the method of claim 36. 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. 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). In this case, Rebulla obtains platelets and administers said platelets to a subject in need thereof, as claimed in claim 36. Although Rebulla does not teach that the platelets are obtained by the method of claim 2, such a product-by-process limitation is not found to necessarily imply a structure that patentably distinguishes the instantly claimed platelets from those found in Rebulla. Indeed, claim 2 describes a process of inducing megakaryocytes to produce platelets, but claim 2 does not expressly limit the platelets themselves. Therefore, absent evidence to the contrary, the product-by-process limitations of claim 36 is not found to overcome the grounds of anticipation by Rebulla. Applicant is respectfully reminded that the Office bears a lesser burden of proof in making a prior art rejection for product-by-process claims because of their peculiar nature than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a patentable difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983). See, MPEP 2113.
Claims 1-7 and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2012/0238020 A1 to Mitchell et al.
This rejection is newly applied, necessitated by amendment.
Mitchell discloses methods of obtaining populations of megakaryocytes and platelets by ex vivo culture of stem cells. Abstract.
The method comprises co-culturing mesenchymal stem cells (MSCs) with CD34+ hematopoietic stem cells in one or more vessels with a media composition comprising an effective amount of stem cell factor (SCF), thrombopoietin (TPO), interleukin-6 (IL-6) and interleukin-11 (IL-11), under conditions to produce megakaryocytes, as claimed in claim 1, and culturing the megakaryocytes in a media comprising one or more ROCK inhibitors, IL-6, TPO and IL-11, as claimed in claim 2. Paragraphs 36-38, 56-57, 62-64, 66-67, 77, 82; Figures 1, 6; claims 1-2, 4-7, 10.
For these reasons, the invention as claimed in claims 1-2 is anticipated by Mitchell.
Regarding dependent claim 3, Mitchell teaches that the CD34+ hematopoietic stem cells are derived from bone marrow or umbilical cord blood (UBC; par. 77), and the mesenchymal stem cells may also be derived from umbilical cord blood (par. 82).
Regarding dependent claim 4, Mitchell teaches the one or more vessels further comprise an effective amount of a ROCK inhibitor (par. 38, 41, 51, 57, 70). Feng teaches that the media composition comprises a ROCK inhibitor (col. 4, ll. 18-24; col. 9, ll. 1-61).
Regarding dependent claim 5, Mitchell teaches the ROCK inhibitor is Y27632, GSK429286a, or fasudil HCl (par. 41).
Regarding dependent claim 6, Mitchell teaches ROCK inhibitors that inhibit ROCK1 and/or ROCK2 (par. 41).
Regarding dependent claim 7, Mitchell does not disclose the media composition contains serum (see, e.g., par. 37-38, 63, 66, 79; claims 5-7).
Regarding dependent claim 36, Mitchell teaches providing an effective amount of the platelets to a subject in need thereof, such as a subject having thrombocytopenia, platelet defects, or bleeding conditions (par. 73).
Claim Rejections - 35 USC § 103
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 18 is rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0238020 A1 to Mitchell et al., as applied to claims 1-7 and 36 above; in view of US 2005/0086710 A1 to Peluso et al.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 18, Mitchell does not teach or fairly suggest the media comprises an effective amount of IL-1β.
Peluso is relevant prior art for discloses a method of preparing platelets, comprising providing hematopoietic progenitor cells, generating megakaryocytes from the hematopoietic progenitor cells, inducing shedding of platelets from the megakaryocytes, and isolating the platelets form the cell culture. Paragraphs 59-66. Peluso teaches that a cytokine cocktail comprising thrombopoietin (TPO), stem cell factor (SCF), interleukin-6 (IL-6) and interleukin-1β (IL-1β) increased generation of platelets relative to other cytokine cocktails tested. Paragraphs 70, 79, 109-110; Figure 1.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Mitchell such that the media further comprises an effective amount of IL-1β, in view of Peluso, with a reasonable expectation of success because the combination of TPO, SCF, IL-6 and IL-1β results in improved generation of platelets from megakaryocytes.
Claims 28 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0238020 A1 to Mitchell et al., as applied to claims 1-7 and 36 above; in further view of Popat et al. (2015) “Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation” Blood, The Journal of the American Society of Hematology, 125(19), 2885-2892.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claims 28 and 30, Mitchell, Feng and Rezania do not teach or fairly suggest that the MSCs, CD34+ cells and/or megakaryocytes are subject to a means of fucosylation.
Popat is relevant prior art for teaching that ex vivo fucosylation of cord-blood (CB) cells improves their homing capacities, leading to faster neutrophil and platelet engraftments. The means of fucosylation included ex vivo incubation of CB cells with the enzyme fucosyltransferase-VI (FT-VI) and guanosine diphosphate (GDP) β-fucose. Abstract; Key Points on pg. 2885; Figure 1.
Popat further teaches that CB cell expansion by co-culture with mesenchymal stromal cells also results in improved neutrophil and platelet engraftment, and therefore ex vivo fucosylation of such expanded CB cells may further accelerate engraftment. Page 2891, right column.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Mitchell to further comprise ex vivo fucosylation of the CD34+ cells by culturing in the presence of a fucosyl-transferase enzyme and a GDP fucose substrate, in view of Popat, with a reasonable expectation of success because ex vivo fucosylation improves platelet engraftment.
Claims 1-7, 17, 31-32, 34-36 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0238020 A1 to Mitchell et al.; in view of US 9,993,503 B2 to Feng et al. (issued: 12-Jun-2018); and US 2020/0080114 A1 to Rezania, Alireza (published: 12-Mar-2020).
This rejection is newly applied, necessitated by amendment.
Mitchell discloses methods of obtaining populations of megakaryocytes and platelets by ex vivo culture of stem cells. Abstract.
The method comprises co-culturing mesenchymal stem cells (MSCs) with CD34+ hematopoietic stem cells in one or more vessels with a media composition comprising an effective amount of stem cell factor (SCF), thrombopoietin (TPO), interleukin-6 (IL-6) and interleukin-11 (IL-11), under conditions to produce megakaryocytes, as claimed in claim 1, and culturing the megakaryocytes in a media comprising one or more ROCK inhibitors, IL-6, TPO and IL-11, as claimed in claim 2. Paragraphs 36-38, 56-57, 62-64, 66-67, 77, 82; Figures 1, 6; claims 1-2, 4-7, 10.
Mitchell does not teach or fairly suggest that the CD34+ cells have been manipulated to comprise a knock-in of HLA class I histocompatibility antigen, alpha chain E (HLA-E), at the genomic locus of β2-microglobulin (β2M), as claimed in claims 31 and 38.
Feng is relevant prior art for teaching methods of producing platelets from megakaryocytes, wherein the megakaryocytes are derived from stem cells (Abstract; col. 3, ll. 45-61). The megakaryocytes or megakaryocyte lineage-specific progenitor cells (MLPs) may be derived from induced pluripotent stem cells, embryonic stem cells, or naturally-occurring CD34+ cells (col. 12, ll. 43-45). The cell culture media comprises TPO, SCF and IL-6 (col. 3, ll. 52-61; col. 4, ll. 28-21). Feng further teaches knocking-out the β2-microglobulin (β2M) gene to generate platelets that are HLA-ABC negative (col. 65, ll. 11-17).
In addition, Rezania is relevant prior art for teaching methods of generating “universal donor cells” that are compatible with any HLA genotype, less susceptible to allogeneic rejection, and/or possess increased survival after transplantation relative to an unmodified cell (Abstract; par. 5, 65). The universal donor cell may be a hematopoietic stem or progenitor cell (HSPC) or a differentiated cell, such as megakaryocytes and platelets (par. 13, 65, 163, 167). The methods of generating universal donor cells comprises genetically-modifying a pluripotent stem cell (PSC) or HSPC by introducing a nucleic acid encoding a tolerogenic factor at the β2M genomic locus, wherein the tolerogenic factor is HLA-E (par. 8, 19, 13, 148).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Mitchell by manipulating the CD34+ cells to comprise knock-in of a nucleic acid encoding HLA-E at the β2M genomic locus, in view of Feng and Rezania, with a reasonable expectation of success because such a modification would generate HSPCs/megakaryocytes/platelets that are HLA-ABC negative and overexpress the tolerogenic factor HLA-E, thereby producing universal donor cells that are less susceptible to allogeneic rejection and/or possess increased survival after transplantation relative to an unmodified cell.
For these reasons, the limitations of claims 1-2, 31 and 38 would have been prima facie obvious over the prior art.
Regarding dependent claim 3, Mitchell teaches that the CD34+ hematopoietic stem cells are derived from bone marrow or umbilical cord blood (UBC; par. 77), and the mesenchymal stem cells may also be derived from umbilical cord blood (par. 82). Feng teaches that the naturally-occurring CD34+ cells are derived from bone marrow or umbilical cord blood (col. 12, 43-45)
Regarding dependent claims 4 and 32, Mitchell teaches the one or more vessels further comprise an effective amount of a ROCK inhibitor (par. 38, 41, 51, 57, 70). Feng teaches that the media composition comprises a ROCK inhibitor (col. 4, ll. 18-24; col. 9, ll. 1-61).
Regarding dependent claim 5, Mitchell teaches the ROCK inhibitor is Y27632, GSK429286a, or fasudil HCl (par. 41). Feng teaches that the ROCK inhibitor is Y27632 (col. 4, ll. 18-24; col. 9, ll. 1-61).
Regarding dependent claim 6, Mitchell teaches ROCK inhibitors that inhibit ROCK1 and/or ROCK2 (par. 41). Feng teaches ROCK inhibitors that inhibit ROCK1 and/or ROCK2 (col. 4, ll. 18-24; col. 9, ll. 1-61).
Regarding dependent claim 7, Mitchell does not expressly disclose that the media composition contains serum (see, e.g., par. 37-38, 63, 66, 79; claims 5-7). Feng teaches that the media composition lacks serum (col. 2, ll. 51-63; col. 16, ll. 31-33; col. 17, ll. 16-25).
Regarding dependent claim 17, Feng discloses that the megakaryocytes are reused to produce additional platelets. See steps 16-18 in Figure 14C, D.
Regarding dependent claims 34-36, Mitchell teaches providing an effective amount of the platelets to a subject in need thereof, such as a subject having thrombocytopenia, platelet defects, or bleeding conditions (par. 73). Feng teaches providing an effective amount of the platelets to a subject in need thereof (col. 37, ll. 45, to col. 38, ll. 14), wherein the subject has thrombocytopenia, trauma, or cancer (col. 5, ll. 6-33; col. 34, ll. 61-64)
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0238020 A1 to Mitchell et al.; US 9,993,503 B2 to Feng et al. (issued: 12-Jun-2018); and US 2020/0080114 A1 to Rezania, Alireza (published: 12-Mar-2020), as applied to claims 1-7, 17, 31-32, 34-36 and 38 above; in further view of US 2005/0086710 A1 to Peluso et al.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 18, Mitchell, Feng and Rezania do not teach or fairly suggest the media comprises an effective amount of IL-1β.
Peluso is relevant prior art for discloses a method of preparing platelets, comprising providing hematopoietic progenitor cells, generating megakaryocytes from the hematopoietic progenitor cells, inducing shedding of platelets from the megakaryocytes, and isolating the platelets form the cell culture. Paragraphs 59-66. Peluso teaches that a cytokine cocktail comprising thrombopoietin (TPO), stem cell factor (SCF), interleukin-6 (IL-6) and interleukin-1β (IL-1β) increased generation of platelets relative to other cytokine cocktails tested. Paragraphs 70, 79, 109-110; Figure 1.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Mitchell such that the media further comprises an effective amount of IL-1β, in view of Peluso, with a reasonable expectation of success because the combination of TPO, SCF, IL-6 and IL-1β results in improved generation of platelets from megakaryocytes.
Claims 28 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0238020 A1 to Mitchell et al.; US 9,993,503 B2 to Feng et al. (issued: 12-Jun-2018); and US 2020/0080114 A1 to Rezania, Alireza (published: 12-Mar-2020), as applied to claims 1-7, 17, 31-32, 34-36 and 38 above; in further view of Popat et al. (2015) “Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation” Blood, The Journal of the American Society of Hematology, 125(19), 2885-2892.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claims 28 and 30, Mitchell, Feng and Rezania do not teach or fairly suggest that the MSCs, CD34+ cells and/or megakaryocytes are subject to a means of fucosylation.
Popat is relevant prior art for teaching that ex vivo fucosylation of cord-blood (CB) cells improves their homing capacities, leading to faster neutrophil and platelet engraftments. The means of fucosylation included ex vivo incubation of CB cells with the enzyme fucosyltransferase-VI (FT-VI) and guanosine diphosphate (GDP) β-fucose. Abstract; Key Points on pg. 2885; Figure 1.
Popat further teaches that CB cell expansion by co-culture with mesenchymal stromal cells also results in improved neutrophil and platelet engraftment, and therefore ex vivo fucosylation of such expanded CB cells may further accelerate engraftment. Page 2891, right column.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Mitchell to further comprise ex vivo fucosylation of the CD34+ cells by culturing in the presence of a fucosyl-transferase enzyme and a GDP fucose substrate, in view of Popat, with a reasonable expectation of success because ex vivo fucosylation improves platelet engraftment.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0238020 A1 to Mitchell et al.; US 9,993,503 B2 to Feng et al. (issued: 12-Jun-2018); and US 2020/0080114 A1 to Rezania, Alireza (published: 12-Mar-2020), as applied to claims 1-7, 17, 31-32, 34-36 and 38 above; in further view of Sullenbarger et al. (2009) “Prolonged continuous in vitro human platelet production using three-dimensional scaffolds” Experimental hematology, 37:101-110.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 33, the claim recites that the CD34+ cells are cultured in the same vessel or substrate that the megakaryocytes produce the platelets.
Prior to the effective filing date of the instantly claimed invention, Sullenbarger discloses a 3D bioreactor system, wherein that the CD34+ cells are cultured and the megakaryocytes produce the platelets in the same vessel or substrate. The medium used to promote megakaryocyte and platelet production contained TPO, SCF and IL-6. Use of the bioreactor system produced greater daily numbers for platelet production relative to the other systems tested. See, e.g., Abstract; pg. 104; fig. 1A, B.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Mitchell such that that the CD34+ cells are cultured in the same vessel or substrate that the megakaryocytes produce the platelets, in view of Sullenbarger, with a reasonable expectation of success because Sullenbarger shows that a bioreactor system, wherein the CD34+ cells are cultured in the same vessel or substrate that the megakaryocytes produce the platelets, produced greater numbers of platelets daily relative to other systems.
Response to Arguments
Applicant’s remarks filed 09/02/2026 have been carefully considered, but are not found persuasive for the following reasons. The arguments are addressed to the extent found relevant to the new grounds of rejection.
Applicant argues that Mitchell does not disclose coculturing CD34+ cells with MSCs. See, pages 6-8 of the reply. The argument is not persuasive because at least paragraphs 14, 37, 67 or 82 describe coculturing CD34+ cells with MSCs.
Applicant argues the combination of Mitchell with Feng with respect to HLA-E knock-in at the β2M because there is no motivation or reasonable expectation of success to make the modification in view of Mitchell and Feng. See, pages 8-10 of the reply. The argument cannot be found persuasive because HLA-E knock-in at the β2M is not a feature claimed by claims 1-7, 17-18, 28, 30 and 36. With respect to claims 31-35 and 38, the argument fails to address the combination and motivation suggested by the Examiner’s rejection because the argument only addresses Mitchell and Feng individually and neglects Rezania.
The remainder of Applicant’s arguments are either sufficiently addressed above or otherwise obviated by the new grounds of rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
De Lima et al. (2012) “Cord-blood engraftment with ex vivo mesenchymal-cell coculture” New England Journal of Medicine, 367(24), 2305-2315, discloses the ex vivo expansion of CD34+ cord-blood cells with mesenchymal stem cells (MSCs), and transplantation thereof into adults with hematologic cancers. See, e.g., Abstract. MSCs naturally sescrete cytokines that influence hematopoiesis, including stem cell factor (SCF), interleukin-6 (IL-6) and thrombopoietin (TPO). See, Supplementary Material, Protocol, pg. 5-7.
Gornalusse et al. (2017) “HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells” Nature biotechnology, 35(8), 765-772, discloses adeno-associated virus (AAV)-mediated gene editing to knock-in HLA-E genes at the beta-2-microglobulin (B2M) genomic locus in human pluripotent stem cells (PSCs). The engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8+ T cells, do not bind to anti-HLA antibodies and are resistant to natural kill (NK) cell-mediated lysis, thus providing “universal donor cells.” See, e.g., Abstract.
US 7,776,591 B2 to Xia et al. (issued: 17-Aug-2010) discloses a method of in vitro fucosylation of selectin ligands on cord blood-derived hematopoietic stem cells (Abstract).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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