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 .
Claims 86-109, of record 7/8/2024, are pending and subject to prosecution.
Priority
The instant application is a CON of 16/769926 (US patent 12161674, filed 6/4/2020)., which is a national stage entry of PCT/US2018/063973 (filed 12/5/2018), which claims benefit of provisional applications 62/594689 (filed 12/5/2017), 62/664023 (filed 4/27/2018), 62/671770 (filed 5/15/2018), 62/734543 (filed 9/21/2018), and 62/734431 (filed 9/21/2018).
Claim Interpretation
Claims 86 and 105 recite a gRNA comprising a nucleotide sequence of SEQ ID NO 1 or SEQ ID NO2 that targets the +58 DHS of the human BCL11A gene. This limitation is interpreted as requiring a gRNA sequence comprising any two or more consecutive nucleotides of instant SEQ ID NO 1 or 2 that is able to target the human BCL11A +58 DHS.
Claim 100 recites the “method of claim 100”. In the interest of compact prosecution, claim 86 is interpreted as depending from independent claim 86 for examination.
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 93-94 and 100 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 93 recites the limitation “wherein the HbF level in the subject is at least 30%”, and claim 94 recites the limitation “wherein the HbF level in the subject is at least 40%”. It is unclear whether the claimed level of HbF is 30% or 40% of total hemoglobin or a percentage of some other entity.
Claim 100 recites the “method of claim 100”. Because a claim cannot depend from itself, the scope of claim 100 cannot be determined.
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.
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.
Claims 86-87 and 101-104 are rejected under 35 U.S.C. 103 as being obvious over Townes et al. (US 20190144888 A1).
Regarding claims 86 and 101-102: Townes et al. teach the genomic editing of cells using CRISPR/Cas9 complexes to correct a mutation in a hemoglobin gene associated with sickle cell disease or β-thalassemia (See ¶0044 and 0052). The edited cell can be a human cell and can be a CD34+ HPC (which reads on “hHSPCs”) (See ¶0049 and 0055). The effective amount of edited cells administered can be about 1 × 106 to about 7 × 106 cells/kg (which would read on “a single dose comprising at least 3 × 106 cells” for a human subject) (See ¶0062). Townes et al. teach editing in a mouse model of sickle cell disease, wherein the gRNA comprised a sequence of instant SEQ ID NO 1 (See ¶0035 and 0148, SEQ ID NO 2, and alignment below).
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Townes et al. do not expressly teach the use of human CD34+ hHSPCs in their examples. However, they teach that mouse fetal liver c-kit+ cells are equivalent to human cord blood CD34+ cells (See ¶0148), which encompass CD34+ hHSPCs. One of ordinary skill in the art would have therefore found it obvious to apply the method of Townes et al. to CD34+ hHSPCs.
Regarding claim 87: Following the discussion of claims 86 and 101-102, Townes et al. teach that the modified cells can be transplanted into a subject that has been treated with busulfan (which reads on “administering busulfan to the subject prior to administering the modified CD34+ hHSPCs”) (See ¶0061).
Regarding claims 103-104: Following the discussion of claims 86 and 101-102, Townes et al. teach that the subject can be an adult (See ¶0063). Townes et al. do not expressly teach the subject as an adolescent, however, they disclose that the subject can also be an infant or newborn (See ¶0053 and 0063). One of ordinary skill in the art would have therefore found it obvious to modify the method of Townes et al. to administer the modified cells to subjects falling within the newborn-to-adult age range, such as adolescents.
Claims 86-88 and 101-104 are rejected under 35 U.S.C. 103 as being obvious over Townes et al. (US 20190144888 A1) in view of Miller (ISBT Science Series, 2017).
The teachings of Townes et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 88: Following the discussion of claims 86-87 and 101-104, Townes et al. teach a method for administering edited hematopoietic stem cells for treating hemoglobinopathies but do not teach further administering red blood cells.
Miller teaches that patients undergoing hematopoietic stem cell transplantation may require pre-, peri- or post-transplant RBC transfusion to treat anemia related to their underlying disease until erythroid engraftment occurs (See page 100, col. 2, ¶1-2 and page 101, col. 2, full ¶1).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Townes et al. to administer peri-transplant RBC transfusions. One would be motivated to make this modification because Miller teaches that it can treat blood disorder-associated anemia until engraftment of transplanted cells takes place (See page 101, col. 2, full ¶1), and such a modification could be readily made.
Claims 86-87 and 101-108 are rejected under 35 U.S.C. 103 as being obvious over Townes et al. (US 20190144888 A1), evidenced by Addgene (Product data sheet, 2026), in view of Scadden et al. (US 20160120947 A1).
The teachings of Townes et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 105-108: Following the discussion of claims 86-87 and 101-104, Townes et al. teach a method for editing hemoglobin genes using CRISPR/Cas9 but do not expressly teach an N-terminal SV40 NLS appended to Cas9.
However, Townes et al. teach the use of a S. pyogenes Cas9 comprising N- and C-terminal NLS that was encoded by Addgene vector 42230 (See ¶0095). Addgene teaches a SV40 NLS located at the N-terminus of the Cas9 transgene in this vector (See product data sheet).
Townes et al. also do not teach the mobilization of CD34+ HPSCs prior to isolation.
Scadden et al. teach methods of mobilizing peripheral blood HSPCs for the treatment of disorders such as sickle cell disease and β-thalassemia (See Abstract and ¶0024). Mobilization can be performed by using a combination of G-CSF and Plerixafor (which reads on “an inhibitor of CXCR4 chemokine receptor”) (See ¶0038, 0048, and 0051).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Townes et al. to comprise mobilization of HPSCs with G-CSF and Plerixafor. One would have been motivated to make this modification because Scadden et al. teach that mobilized hematopoietic stem cells have improved transplantation outcomes compared to bone marrow-derived hematopoietic stem cells (See ¶0003). There would be a reasonable expectation of success in doing so because subjects in the method of Townes et al. could be readily treated with mobilization agents.
Regarding claim 109: Following the discussion of claims 86-87 and 101-104, Townes et al. do not teach the collection of at least 15 × 106 mobilized CD34+ hHSPCs/kg.
However, Scadden et al. teach that a single session of apheresis can collect a mobilized cell dose of between about 2 × 106/kg and 10 × 106/kg of the recipient’s body weight (See ¶0027 and 0033). Because Townes et al. demonstrate that editing efficiency of hemoglobin genes is no better than approximately 60% (See fig. 16A), this renders obvious the collection of a larger total number of CD34+ stem cells, which would approach the claimed amount, in order to ensure a dose of about 2 × 106 and 10 × 106/modified cells/kg. Where the claimed ranges overlap with the prior art or are merely close, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claims 86, 100-102, and 105-108 are rejected under 35 U.S.C. 103 as being obvious over Cowan et al. (US 20200330609 A1), of record in IDS dated 4/4/2025.
The applied reference has a common assignee and joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Regarding claim 86: Cowan et al. teach materials and methods for treating hemoglobinopathies (See Abstract). The BCL11A +58 DNA hypersensitive site can be edited by introducing into CD34+ cells one or more DNA endonucleases (See ¶0010, 0027, and 0033). Cells can be edited with a S. pyogenes Cas9 and a modified sgRNA having a nucleic acid sequence identical to the sequence of instant SEQ ID NO 1 (See ¶0030, SEQ ID NO 71959, and alignment below).
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Cowan et al. do not expressly teach an embodiment wherein a single dose comprises at least 3 × 106 hHSPCs, however, they teach that an effective dose can comprise at least 3 × 106 progenitor cells (See ¶0486). It therefore would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Cowan et al. to comprise a dose of at least 3 × 106 edited hHSPCs, as Cowan et al. indicate that it could comprise an effective dose.
Regarding claim 100: Following the discussion of claim 86, Cowan et al. teach that editing can be used to ameliorate symptoms of hemoglobinopathies, such as bone and chest pain (which reads on “reduction over time in pai in the subject”) (See ¶0490).
Regarding claims 101-102: Following the discussion of claim 86, Cowan et al. teach that the hemoglobinopathies that can be treated are sickle cell anemia (which reads on “sickle cell disease”) and β-thalassemia (See ¶0009).
Regarding claim 105: Following the discussion of claim 86, Cowan et al. teach an example wherein mobilized CD34+ cells from patients were collected and electroporated with Cas9 mRNA and sgRNA comprising the sequence of instant SEQ ID NO 1 (SPY101 sgRNA) (See ¶0169 and 0658).
Cowan et al. do not expressly teach Cas9 as comprising an NLS. However, Cowan et al. teach that the DNA endonuclease can be flanked at the N- and/or C-terminus by a SV40 NLS (See ¶0029).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Cowan et al. to comprise a Cas9 having a N-terminal SV40 NLS. Combining prior art elements according to known methods to yield predictable results is considered to be prima facie obvious. See MPEP 2143(I)(A). One of ordinary skill would readily recognize that the SV40 NLS could be used to target Cas9 to the nucleus in a predictable manner.
Regarding claims 106-108: Following the discussion of claims 86 and 105, Cowan et al. teach that hHSPCs can be isolated after the patient is treated with a granulocyte colony stimulating factor, optionally in combination with Plerixafor (which reads on “an inhibitor of CXCR4 chemokine receptor”) (See ¶0216).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See, generally, MPEP 717.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP 2159. See MPEP 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 86-88 and 91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-9, 12, and 14-16 of U.S. Patent No. 12161674. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 86: Patented claim 1 recites a composition comprising a single dose of CD34+ human hematopoietic stem and progenitor cells (hHSPCs) that comprise a genetic modification within a +58 DNase I hypersensitive site (DHS) within the erythroid lineage-specific enhancer of a human B-cell lymphoma 11A (BCL11A) gene (modified CD34+ hHSPCs), wherein the single dose comprises an effective amount to result in an absence of vaso-occlusive crises (VOCs) for at least 12 months after administration of the hHSPCs, wherein the genetic modification is produced by delivering to the CD34+ hHSPCs a Cas9 endonuclease and a guide RNA (gRNA) comprising a nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and wherein the single dose comprises a minimum dose of 3×106 CD34+ hHSPCs per kg. Patented claim 5 recites the composition of patented claim 1, wherein the genetic modification is produced by delivering to the CD34+ hHSPCs a Cas9 endonuclease and a guide RNA (gRNA) comprising the nucleotide sequence of SEQ ID NO: 1. Patented claim 6 recites the composition of patented claim 1, wherein the genetic modification is produced by delivering to the CD34+ hHSPCs a Cas9 endonuclease and a guide RNA (gRNA) comprising the nucleotide sequence of SEQ ID NO: 2. While the patented claims do not expressly teach a method of treating a subject, the limitation “wherein the single dose comprises an effective amount to result in an absence of vaso-occlusive crises” in patented claim 1 renders obvious the use of the composition in a method of treating a subject having a hemoglobinopathy.
Patented claim 7 recites a method comprising administering to a subject having a hemoglobinopathy a single dose of CD34+ human hematopoietic stem and progenitor cells (hHSPCs) that comprise a genetic modification within a +58 DNase I hypersensitive site (DHS) within the erythroid lineage-specific enhancer of a human B-cell lymphoma 11A (BCL11A) gene (modified CD34+ hHSPCs), wherein the single dose comprises an effective amount to result in an absence of vaso-occlusive crises (VOCs) for at least 12 months after administration of the hHSPCs, wherein the genetic modification is produced by delivering to the CD34+ hHSPCs a Cas9 endonuclease and a guide RNA (gRNA) comprising a nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2, and wherein the single dose comprises a minimum dose of 3×106 CD34+ hHSPCs per kg. Patented claim 14 recites the method of patented claim 7, wherein the dose is 3×106 CD34+ hHSPCs per kg. Patented claim 15 recites the method of patented claim 7, wherein the genetic modification is produced by delivering to the CD34+ hHSPCs a Cas9 endonuclease and a guide RNA (gRNA) comprising the nucleotide sequence of SEQ ID NO: 1. Patented claim 16 recites the method of patented claim 7, wherein the genetic modification is produced by delivering to the CD34+ hHSPCs a Cas9 endonuclease and a guide RNA (gRNA) comprising the nucleotide sequence of SEQ ID NO: 2. The patented claims anticipate the instant claim.
Regarding claim 87: Following the discussion of claim 86, patented claim 9 recites the method of claim 7, further comprising administering busulfan to the subject.
Regarding claim 88: Following the discussion of claim 86, patented claim 8 recites the method of claim 7, further comprising administering red blood cells to the subject.
Regarding claim 91: Following the discussion of claim 86, patented claim 12 recites the method of claim 7, wherein (i) the subject requires fewer blood transfusions within a two-year period of the time of administration of the modified CD34+ hHSPCs, or within a two-year period after the time of administration of the modified CD34+ hHSPCs, relative to a two-year period before the time of administration of the modified CD34+ hHSPCs; (ii) the subject achieves transfusion reduction or transfusion independence for at least three months following administration of the modified CD34+ hHSPCs starting three months after administration of the modified CD34+ hHSPCs; (iii) the subject achieves transfusion reduction or transfusion independence for at least six months following administration of the modified CD34+ hHSPCs starting three months after administration of the modified CD34+ hHSPCs; (iv) the subject achieves transfusion reduction or transfusion independence for at least twelve months following administration of the modified CD34+ hHSPCs starting three months after administration of the modified CD34+ hHSPCs; (v) the subject is no longer in need of iron chelation therapy within a 2 to 5 year period of the time of administration of the modified CD34+ hHSPCs, or within a 2 to 5 year period after the time of administration of the modified CD34+ hHSPCs, relative to a 2 to 5 year period before the time of administration of the modified CD34+ hHSPCs; and/or (vi) the HbF level in the subject is at least 20% for at least three months starting at any time at or after the time of administration of the modified CD34+ hHSPCs. The patented claim renders obvious the instant claim.
Claims 86, 101-102, and 105 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 94, 98-99, 101, and 105-109 of co-pending Application No. 19183148 (reference application) in view of Townes et al. (US 20190144888 A1) and Scadden et al. (US 20160120947 A1).
The teachings of Townes et al. and Scadden et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claims 86, 101-102 and 105: Co-pending claim 94 recites a single-molecule guide RNA (sgRNA) comprising the nucleic acid sequence of SEQ ID NO: 71,959 (which is identical to instant SEQ ID NO 1, see alignment below), wherein the sgRNA comprises three 2'O-methyl-phosphorothioate residues at each of its 5' and 3' ends.
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Co-pending claim 98 recites the sgRNA of co-pending claim 94, a nucleic acid comprising a nucleotide sequence encoding said sgRNA, or a vector comprising said nucleic acid, for use in treating a patient with hemoglobinopathy. Co-pending claim 99 recites the sgRNA, nucleic acid, or vector for use according to co-pending claim 98, wherein the hemoglobinopathy is sickle cell anemia or thalassemia. Co-pending claim 101 recites an ex vivo method of editing a B-cell lymphoma 11A (BCL11A) gene in a human cell by genome editing, the method comprising: introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases or a nucleic acid comprising a nucleotide sequence encoding the one or more DNA endonucleases or a vector comprising said nucleic acid to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the BCL11A gene or other DNA sequence that encodes a regulatory element of the BCL11A gene, that results in a permanent deletion, modulation, or inactivation of a transcriptional control sequence of the BCL11A gene, wherein the method further comprises introducing into the cell the sgRNA of co-pending claim 94, a nucleic acid comprising a nucleotide sequence encoding the nucleic acid sequence of said sgRNA, or a vector comprising said nucleic acid, and wherein the one or more DNA endonucleases comprises a Cas9 endonuclease. Co-pending claim 105 recites the method of co-pending claim 101, wherein the one or more DNA endonucleases is pre-complexed with the sgRNA to form one or more ribonucleoproteins (RNPs), wherein the one or more DNA endonucleases is combined with the sgRNA in a weight ratio of 1:1 DNA endonuclease to sgRNA to form the one or more RNPs. Co-pending claim 106 recites the method of co-pending claim 105, wherein the one or more RNPs are delivered to the human cell by electroporation. Co-pending claim 107 recites the method of co-pending claim 106, wherein the one or more DNA endonucleases is a S. pyogenes Cas9 comprising a N-terminus SV40 NLS and a C-terminus SV40 NLS. Co-pending claim 108 recites the method of co-pending claim 107, wherein the human cell is a hematopoietic progenitor cell. Co-pending claim 109 recites the method of co-pending claim 108, wherein the hematopoietic progenitor cell is a CD34+ cell. The co-pending claims do not recite a minimum dose of 3×106 CD34+ hHSPCs per kg or mobilization of the CD34+ cells prior to collection.
Townes et al. teach genomic editing of cells using CRISPR/Cas9 complexes to correct a mutation in a hemoglobin gene associated with sickle cell disease or β-thalassemia (See ¶0044 and 0052). The edited cell can be a human cell and can be a CD34+ HPC (which reads on “hHSPCs”) (See ¶0049 and 0055). The effective amount of edited cells administered can be about 1 × 106 to about 7 × 106 cells/kg (which reads on “at least 3 × 106”) (See ¶0062).
Scadden et al. teach methods of mobilizing peripheral blood HSPCs for the treatment of disorders such as sickle cell disease and β-thalassemia (See Abstract and ¶0024). Mobilization can be performed by using a combination of G-CSF and Plerixafor (which reads on “an inhibitor of CXCR4 chemokine receptor”) (See ¶0038, 0048, and 0051).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of the co-pending claims to comprise a dose of 1 × 106 to about 7 × 106 cells/kg. One would have been motivated to make this modification because Townes et al. teach that such amounts can constitute an effective dose (See ¶0062).
It also would have been obvious to modify the method of the co-pending claims to comprise mobilization of HPSCs with G-CSF and Plerixafor. One would have been motivated to make this modification because Scadden et al. teach that mobilized hematopoietic stem cells have improved transplantation outcomes compared to bone marrow-derived hematopoietic stem cells (See ¶0003). There would be a reasonable expectation of success in doing so because subjects in the method of co-pending claims could be readily treated with mobilization agents.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 89-92 and 95-99 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The prior art does not appear to teach or suggest a method of treating a subject having a hemoglobinopathy with CD34+ hHSPCs edited using gRNA comprising either instant SEQ ID NO, wherein the method yields the claimed functional limitations.
Conclusion
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
