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 1, 31, 33-40, 45, and 47-55, of record 12/16/2025, are pending and subject to prosecution. Claims 1, 31, 33, 37, 40, 45, and 48 are amended. Claims 3 and 46 are cancelled. Claims 53-55 are newly added.
Status of Prior Rejections/Response to Arguments
RE: Objection to claim 37:
The amendment to claim 37 is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claim 46 under 35 U.S.C. 112(b):
The cancellation of claim 46 renders the rejection thereto moot.
RE: Rejection of claims 1, 3, and 31 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Gori et al. (WO 2019178426 A1):
RE: Rejection of claims 1, 3, 31, and 40 under 35 U.S.C. 103 over Gori et al. (WO 2019178426 A1):
The cancellation of claim 3 renders the rejections thereto moot.
The applicant asserts that the amendment to claim 1 to require the enumerated deletions at the enumerated percentages in a HBG gene promoter is not disclosed by Gori et al. (Applicant Remarks, page 13-15).
This argument is not found persuasive. The instant specification teaches that editing of CD34+ cells using RNP32 (comprising a gRNA comprising the sequence set forth in SEQ ID NO 1051 and a Cpf1 variant protein encoded by the sequence set forth in SEQ ID NO 1097) (See table 15) generates a HBG1/2 -104 to -121 deletion comprising 15.1% of the indels, a HBG1/2 -110 to -115 deletion comprising 6.92% of the indels, a HBG1/2 -112 to -115 deletion comprising 5.53% of the indels, a HBG1/2 -113 to -115 deletion comprising 4.18% of the indels, a HBG1/2 -111 to -115 deletion comprising 3.19% of the indels, a HBG1/2 -111 to -117 deletion comprising 3.10% of the indels, a HBG1/2 -102 to -114 deletion comprising 2.63% of the indels, a HBG1/2 -114 to -118 deletion comprising 2.07% of the indels, a HBG1/2 -112 to -116 deletion comprising 1.72% of the indels, and a HBG1/2 -113 to -117 deletion comprising 1.54% of the indels (See table 25). Fig. 43C shows that only 11.90% of the indels generated by 72 h post-electroporation of RNP32 are 3 bp or less (which reads on “60% or more of the indels in the plurality of unmodified cells as a whole are deletions of at least 4 base pairs”) (See ¶0127 and fig. 43C). The RNP32-treated cells also demonstrate reduced sickling (See fig. 52).
Gori et al. teach that an RNP complex may include a gRNA comprising the sequence set forth in SEQ ID NO 1051 and a modified Cpfl protein encoded by the sequence set forth in SEQ ID NO 1097, represented by RNP32 (See ¶0018-0020 and table 21). SEQ ID NO 1051 comprises equivalent nucleotide sequences in the instant application and in the teachings of Gori et al. (See alignment below), who note that “T” denotes thymine or uracil in instances where a sequence may be encoded by DNA or RNA (See ¶0154). A person or ordinary skill in the art would also understand a gRNA to comprise uracil bases.
PNG
media_image1.png
166
580
media_image1.png
Greyscale
The sequence of SEQ ID NO 1097 taught by Gori et al. is identical to that of SEQ ID NO 1097 in the instant application (See alignment below (first 120 aa displayed)).
PNG
media_image2.png
170
580
media_image2.png
Greyscale
The use of RNP32 as taught by Gori et al. would therefore inherently produce the claimed deletions in a HBG gene promoter in at least 60% of the cells, thereby reducing sickling. Inherent features need not be recognized or disclosed by the prior art in order to be anticipatory. See MPEP 2112(I)-(II).
The rejections are maintained in modified form to address the amended limitations.
RE: Rejection of claims 1, 3, 31, 33, 38-40, 45, and 47-52 under 35 U.S.C. 103 over Gori et al. (WO 2019178426 A1) in view of Akinsheye et al. (Blood, 2011):
RE: Rejection of claims 1, 3, 31, 33-36, 38-40, 45, and 47-52 under 35 U.S.C. 103 over Gori et al. (WO 2019178426 A1) in view of Akinsheye et al. (Blood, 2011), further in view of Rab et al. (HemaSphere, 2019):
RE: Rejection of claims 1, 3, 31, 33, 37-40, 45, and 47-52 under 35 U.S.C. 103 over Gori et al. (WO 2019178426 A1) in view of Akinsheye et al. (Blood, 2011), further in view of Lu et al. (American Journal of Hematology, 2018):
The cancellation of claim 3 renders the rejections thereto moot.
Upon further consideration, the 103 rejections are withdrawn in favor of the rejections over only Gori et al.
RE: Provisional rejection of claims 3, 31, and 33-38 on the ground of nonstatutory double patenting over claims 5, 31, and 33-38 of copending Application No. 18/893308:
The cancellation of claim 3 renders the provisional rejection thereto moot.
Applicants are reminded that 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office Action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Non-statutory double patenting rejections may not be held in abeyance. See MPEP 714.02. Applicants did not traverse the NSDP rejection. The rejection is maintained in modified form to address amended limitations.
New/Maintained Rejections
Claim Interpretation
Claim 33 recites the limitation “the first population of RBCs exhibiting significantly decreased sickling upon deoxygenation than a second population of RBCs comprising a plurality of RBCs cultured from the first population of unmodified cells”. Claim 33 does not recite an active step of deoxygenation, therefore this limitation is interpreted as requiring the first population of RBCs to exhibit decreased sickling only if subjected to deoxygenation.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 31, and 55 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gori et al. (WO 2019178426 A1), of record.
Gori et al. teach CRISPR-mediated methods of editing the HBG1 and HBG2 loci to increase expression of fetal hemoglobin (See Abstract).
Regarding claims 1 and 31: Gori et al. teach the ex vivo editing of hematopoietic stem cells or mobilized CD34+ cells (See ¶0031 and 0097-0099 and fig. 26-28). The cells can be edited with an RNP complex that may include a gRNA comprising the sequence set forth in SEQ ID NO 1051 and a modified Cpfl protein encoded by the sequence set forth in SEQ ID NO 1097, represented by RNP32 (See ¶0018-0020 and table 21). The edited cells can differentiate into erythroid cells (See ¶0440). Gori et al. do not expressly teach the edited cells as comprising the enumerated indels.
The instant specification teaches that editing of CD34+ cells using RNP32 (comprising a gRNA comprising the sequence set forth in SEQ ID NO:1051 and a Cpf1 variant protein encoded by the sequence set forth in SEQ ID NO:1097) (See table 15) generates a HBG1/2 -104 to -121 deletion comprising 15.1% of the indels, a HBG1/2 -110 to -115 deletion comprising 6.92% of the indels, a HBG1/2 -112 to -115 deletion comprising 5.53% of the indels, a HBG1/2 -113 to -115 deletion comprising 4.18% of the indels, a HBG1/2 -111 to -115 deletion comprising 3.19% of the indels, a HBG1/2 -111 to -117 deletion comprising 3.10% of the indels, a HBG1/2 -102 to -114 deletion comprising 2.63% of the indels, a HBG1/2 -114 to -118 deletion comprising 2.07% of the indels, a HBG1/2 -112 to -116 deletion comprising 1.72% of the indels, and a HBG1/2 -113 to -117 deletion comprising 1.54% of the indels (See table 25). Fig. 43C shows that only 11.90% of the indels generated by 72 h post-electroporation of RNP32 are 3 bp or less (which reads on “60% or more of the indels in the plurality of unmodified cells as a whole are deletions of at least 4 base pairs”) (See ¶0127 and fig. 43C). The RNP32-treated cells also demonstrate reduced sickling (See fig. 52).
SEQ ID NO 1051 comprises equivalent nucleotide sequences in the instant application and in the teachings of Gori et al. (See alignment below), who note that “T” denotes thymine or uracil in instances where a sequence may be encoded by DNA or RNA (See ¶0154). A person or ordinary skill in the art would also understand a gRNA to comprise uracil bases.
PNG
media_image1.png
166
580
media_image1.png
Greyscale
The sequence of SEQ ID NO 1097 taught by Gori et al. is identical to that of SEQ ID NO 1097 in the instant application (See alignment below (first 120 aa displayed)).
PNG
media_image2.png
170
580
media_image2.png
Greyscale
Use of RNP32 for editing CD34+ cells, as taught by Gori et al., would inherently yield cells having the claimed limitations, thereby anticipating the claimed invention. The prior art need not recognize or disclose inherent features in order for the prior art to anticipate the claimed invention. See MPEP 2112(I)-(II).
Regarding claim 55: Following the discussion of claims 1 and 31, Gori et al. teach that the gRNA may comprise a gRNA targeting domain, such as the sequence of SEQ ID NO 1254 (See ¶0018). SEQ ID NO 1051 comprises the sequence of SEQ ID NO 1254 (See alignment below).
PNG
media_image3.png
106
580
media_image3.png
Greyscale
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, 31, 33-40, 45, and 47-55 are rejected under 35 U.S.C. 103 as being unpatentable over Gori et al. (WO 2019178426 A1), of record.
The teachings of Gori et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 33-36, 45, 47, and 50-52: Following the discussion of claims 1, 31, and 55, Gori et al. teach the editing of CD34+ cells by electroporation of an RNP comprising a gRNA comprising the sequence set forth in SEQ ID NO:1051 and a Cpf1 variant protein encoded by the sequence set forth in SEQ ID NO:1097) (See ¶0123 and 0428, fig. 52, and table 21) but do not expressly teach generating RBCs using the RNP or the resulting RBCs as exhibiting decreased sickling.
However, Gori et al. teach the in vitro differentiation of hematopoietic stem and progenitor cells or mobilized peripheral blood CD34+ cells treated with other RNPs to erythroid cells in order to analyze genomic editing in the progeny (See ¶0386 and 0389). It would have been obvious to one of ordinary skill in the art to culture RMP32-edited cells similarly until the terminally differentiated form is reached, for monitoring indels as well as phenotype, as Gori et al. teach that erythrocytes are the cells phenotypically affected by hemoglobinopathies (See ¶0174).
The instant specification teaches that RNP32-edited cells have reduced sickling upon exposure to sodium metabisulfite (which reads on “deoxygenation”) (See ¶0136 and fig. 52). The instant specification also teaches that the RNP32-edited cells from sickle cell disease patients exhibited a higher minimum elongation index and that the edited cells start to sickle at lower relative oxygen pressure compared to the patients’ unedited cells (See ¶0458 and fig. 53). The RNP32-edited cells of Gori et al. would inherently possess these characteristics.
Regarding claim 37: Following the discussion of claims 1, 31, 33-36, 45, 47, 51-52, and 55, Gori et al. do not expressly teach the deoxygenated velocity of RNP32-edited cells. However, the instant specification discloses that the velocity of RNP-treated cells from sickle cell disease patients undergo less of a drop in velocity through microchannels upon deoxygenation (See ¶0459 and fig. 54). The RNP32-edited cells of Gori et al. would inherently possess this characteristic.
Regarding claim 38: Following the discussion of claims 1, 31, 33-36, 45, 47, 51-52, and 55, Gori et al. are silent on the fetal hemoglobin levels in RNP32-edited cells. However, the instant specification discloses that RNP32-edited cells from sickle cell disease patients express higher levels of fetal hemoglobin than unedited cells (See fig 51). The RNP32-edited cells of Gori et al. would inherently possess this characteristic.
Regarding claim 39: Following the discussion of claims 1, 31, 33-36, 45, 47, 51-52, and 55, Gori et al. teach that the gRNA may comprise a gRNA targeting domain, such as the sequence of SEQ ID NO 1002 (See ¶0018). SEQ ID NO 1051 comprises the sequence of SEQ ID NO 1002 (See alignment below).
PNG
media_image4.png
110
580
media_image4.png
Greyscale
Regarding claim 40: Following the discussion of claims 1, 31, 33-39, 45, 47, 50-52, and 55, Gori et al. teach the editing of CD34+ cells with RNP32 to reduce sickling but do not expressly teach administration of the edited cells to a subject.
However, Gori et al. teach that HBG promoter-edited cells can be administered to a subject in order to alleviate one or more symptoms of sickle cell disease (See ¶0032).
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 Gori et al. to comprise administration of RNP32-edited cells to a subject having sickle cell disease. One would be motivated to make this modification in order to reduce symptoms associated with the disease (See ¶0020). There would be a reasonable expectation of success in doing so because Gori et al. teach that the edited cells can be administered for this purpose (See ¶0020).
Regarding claims 48-49 and 53-54: Following the discussion of claims 1, 31, 33-39, 45, 47, 50-52, and 55, Gori et al. teach the editing of CD34+ cells with RNP32 to reduce sickling but do not expressly teach the gRNA as comprising a 5’ end DNA extension or a 3’ end phosphorothioate modification or 2’-O-methyl modification, and/or a 2’ fluoro modification.
However, Gori et al. teach that the gRNA can comprise one or more modifications, including a 3’ end phosphorothioate linkage modification, a 3’ end 2’-O-methyl modification, and a 5’ end DNA extension (See ¶0020 and 0033). DNA extension may comprise a sequence set forth in SEQ ID NOs 1235-1250 (See ¶0020).
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 gRNA of Gori et al. to comprise one or more modifications. One would be motivated to make this modification because Gori et al. teach that such gRNA modifications may increase editing of target nucleic acids that result in an increase of productive indels (See ¶0020). Such a modification could be readily performed.
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 1, 31, and 33-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31, 33-38, and 47 of copending Application No. 18/893308 (reference application).
The instant application shares the same effective filing date as the 18/893308 application. Because the instant application shares the same effective filing date as the ‘308 application, if a double patent rejection is warranted and made, the rejection can only be overcome by a showing that the claims are patentably distinct or by filing a terminal disclaimer.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claims 1 and 31: Co-pending claim 31 recites a method of inducing expression of fetal hemoglobin (HbF) in a first population of modified cells comprising a plurality of modified CD34+ or hematopoietic stem cells, the method comprising: delivering a first RNP complex including a first guide RNA (gRNA) and a Cpf1 RNA-guided nuclease or a modified Cpf1 RNA-guided nuclease to a first population of unmodified cells comprising a plurality of unmodified CD34+ or hematopoietic stem cells to generate indels, the first gRNA including a first gRNA targeting domain, each modified CD34+ or hematopoietic stem cell comprising an indel in an HBG gene promoter, 60% or more of the indels in the plurality of modified cells as a whole are deletions of at least 4 base pairs; the first population of modified cells comprising higher HbF levels than the first population of unmodified cells. Co-pending claim 47 recites the method of inducing expression of HbF of claim 31, wherein the plurality of modified cells as a whole comprise the following deletions: a HBG1/2 c.-104 to -121 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-104 to -121 deletion making up 1% to 15.5% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-110 to -115 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-110 to -115 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-112 to -115 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-112 to -115 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-113 to -115 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-113 to -115 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-111 to -115 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-111 to -115 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-111 to -117 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-111 to -117 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-102 to -114 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-102 to -114 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-114 to -118 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-114 to -118 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; a HBG1/2 c.-112 to -116 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-112 to -116 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole; and a HBG1/2 c.-113 to -117 deletion in a HBGI promoter, HBG2 promoter, or a combination thereof, the HBG1/2 c.-113 to -117 deletion making up 1% to 6% of the indels in the plurality of modified cells as a whole. The combined methods of the co-pending claim render obvious the instant claim.
Regarding claim 33: Following the discussion of claims 1 and 31, co-pending claim 33 recites method of decreasing sickling in a first population of red blood cells (RBCs) cultured from a first population of modified cells comprising a plurality of modified CD34+ cells from a subject having sickle cell disease, the method comprising: a) delivering a first RNP complex including a first gRNA and a Cpf1 RNA-guided nuclease or a modified Cpf1 RNA-guided nuclease to a first population of unmodified cells comprising a plurality of unmodified CD34+ cells from the subject to generate indels, the first gRNA including a first gRNA targeting domain, each modified CD34+ cell comprising an indel in an HBG gene promoter, 60% or more of the indels in the plurality of modified CD34+ cells as a whole are deletions of at least 4 base pairs; and b) culturing the first population of RBCs from the first population of cells comprising the plurality of modified CD34+ cells, the first population of RBCs exhibiting significantly decreased sickling upon deoxygenation than a second population of RBCs comprising a plurality of RBCs cultured from the first population of unmodified cells. The combined methods of the co-pending claim render obvious the instant claim.
Regarding claim 34: Following the discussion of claims 1, 31, and 33, co-pending claim 34 recites the method of decreasing sickling of claim co-pending 33, wherein the first population of RBCs sickle at a significantly lower oxygen tension than the second population of RBCs. The combined methods of the co-pending claim render obvious the instant claim.
Regarding claim 35: Following the discussion of claims 1, 31, and 33, co-pending claim 35 recites the method of decreasing sickling of co-pending claim 34, wherein the oxygen tension is measured by relative oxygen pressure. The combined methods of the co-pending claim render obvious the instant claim.
Regarding claim 36: Following the discussion of claims 1, 31, and 33, co-pending claim 36 recites the method of decreasing sickling of co-pending claim 33, wherein the first population of RBCs has a significantly higher minimum elongation index upon deoxygenation than the second population of RBCs. The combined methods of the co-pending claim render obvious the instant claim.
Regarding claim 37: Following the discussion of claims 1, 31, and 33, co-pending claim 37 recites the method of decreasing sickling of co-pending claim 33, wherein the first population of RBCs have a significantly higher velocity upon deoxygenation than a second population of RBCs comprising a plurality of RBCs cultured from the first population of unmodified cells. The combined methods of the co-pending claim render obvious the instant claim.
Regarding claim 38: Following the discussion of claims 1, 31, and 33, co-pending claim 38 recites the method of decreasing sickling of co-pending claim 33, wherein the first population of RBCs comprises higher HbF levels than a second population of RBCs comprising a plurality of RBCs cultured from the first population of unmodified cells. The combined methods of the co-pending claim render obvious the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633