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 .
1. Original claims 1-27 are pending and under examination.
Claim Objections
2. Claims 6-27 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend upon another multiple dependent claim. See MPEP § 608.01(n).
3. Claim 1 should be rewritten as follows:
A method of transducing a population of hematopoietic stem or progenitor cells mobilized from the bone marrow into the peripheral blood of a mammalian subject, the method comprising:
a. administering a CXCR2 agonist selected from the group consisting of
Gro- β, Gro-β T, and variants thereof to mobilize the hematopoietic stem or progenitor cells into the peripheral blood of a mammalian subject, where the CXCR2 agonist is administered at a dose of about 0.001 mg/kg to about 0.1 mg/kg or at a fixed dose of about 1 mg to about 8 mg,
b. administering to the subject a nucleic acid comprising a selection marker to transduce the mobilized hematopoietic stem or progenitor cells in vivo, and
c. administering a selection agent to select for the hematopoietic stem or progenitor cells that have been transduced with the nucleic acid comprising the selection marker, whereby hematopoietic stem or progenitor cells that have not been transduced with the nucleic acid comprising the selection marker do not survive.
4. Claim 2 is objected to because of the recitation “The method of any preceding claims”. Correction to “the method of claim 1” is required.
5. Claims 11 and 12 are objected to because of the recitation “after administration of the” in line 2. Correction to “after the administration of the” is required.
7. Claims 13, 15, 19-23, and 25-27 are objected to because of the recitation “was”. Correction to replace this recitation with “is” is required.
8. Claims 17, 24, and 25 are objected to because of the recitation “were”. Correction to replace this recitation with “are” is required.
Claim Rejections - 35 USC § 112(b)
9. 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.
10. Claim 11 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.
Claim 11 recites the limitation "the CXCR4 agonist" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(d)
11. 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.
12. Claims 14 and 16 are 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.
Claim 14 recites that the CXCR2 agonist comprises Gro-β T. However, the parent claims recite that the CXCR2 agonist is “selected from the group consisting of
Gro-β, Gro-β T, and variants thereof”. Claim 14 broadens the subject matter of the parent claims because the recitation “comprises Gro-β T” encompasses Gro-β T together with agonists other than Gro-β and variants thereof.
By reciting “administering the CXCR2 agonist, claim 16 fails to further limit the subject matter of the parent claim 1 which already recites this limitation and of claims 2-15 which encompass this limitation via their dependency upon claim 1.
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 § 103
13. 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.
14. Claims 1 and 4-27 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (J.C.I. February 2009, 129: 598-615), in view of Hoggatt et al. (Methods and Protocols, Meth. Mol. Biol., 2012, 904: 49-67), as evidenced by both Li et al. (Mol. Ter.: Methods & Clinical Development, 2018, 142-152) and King et al. (Blood, 2001, 97: 1534-1541).
Wang et al. teach in vivo transducing hematopoietic stem/progenitor cells (HSPCs) in a mammalian subject, the method comprising: (1) administering to the subject a combination of G-CSF and AMD3100 (i.e., plerixafor) to mobilize the HSPCs from the bone marrow into the peripheral blood; (2) intravenously administering HDAd5/35++ (comprising the MGMT selection marker and the human [Symbol font/0x67]-globin gene) and HDAd-SB (encoding the Sleeping Beauty transposase 100x or SB100x) at 30 or 60 min post plerixafor administration; the MGMT selection marker allows for the specific in vivo selection of the transduced HSPCs with O6BG, BCNU or temozolomide; and (3) selecting for the transduced HSPCs by administering the selection marker 4 weeks post HDAd5/35++/HDAd-SB administration (claims 1-5, 7-12, and 16-18) (see Abstract; p. 599-600; p. 612, column 2).
Wang et al. teach that the HDAd5/35++ is that disclosed by Li et al. (see p. 611, column 2, last paragraph). As evidenced by Li et al., the MGMT in the HDAd5/35++ vector is a mutated MGMT (claim 6) (see p. 143, paragraph bridging columns 1 and 2).
Wang et al. teach G-CSF and not Gro-β T (claims 1 and 14). Hoggatt et al. teach that G-CSF is associated with several disadvantages and that using Gro-β[Symbol font/0x44]4 enhances engraftment and long-term repopulating abilities of HSPCs (see Abstract; paragraph bridging p. 52 and 53; p. 53; p. 60). Based on these teachings, one of skill in the art would have found obvious to modify Wang et al. by replacing G-CSF with Gro-β[Symbol font/0x44]4 to achieve the predictable result of obtaining transduced HSPCs exhibiting enhanced engraftment and long-term repopulating abilities. Hoggatt et al. teach that
Gro-β[Symbol font/0x44]4 is the same as SB-251353 taught by King et al. (see Table 1 on p. 54). As evidenced by King et al., SB-251353 is an N-terminally 4-amino acid truncated form of Gro-β (see Abstract; p. 1534, column 1, second paragraph). Thus, Gro-β[Symbol font/0x44]4 is Gro-β T (see also [0106] in the specification for definition of Gro-β T).
With respect to claims 20-23, Hoggatt et al. teach that Gro-β T could be administered 45 min after or simultaneously with plerixafor administration (see p. 53; p. 55, Fig. 1).
With respect to the doses and administration schedules recited in claims 1, 13, 15, 19, and 24-27, one of skill in the art would have found obvious to use routine experimentation and vary the method parameters with the reasonable expectation that doing so would identify the optimal conditions for HSPCs mobilization into the peripheral blood. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed doses and administration schedules was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
MPEP 2144.05 III A states that "[a] modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In this case, there is no evidence of a difference in kind or even degree when using the claimed doses and schedules.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
15. Claims 1-27 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. taken with Hoggatt et al. as evidenced by both Li et al. and King et al., in further view of Gonzalez et al. (PNAS, 2008, 106: 8918-8922).
The teachings of Wang et al. and Hoggatt et al. are applied as above for claims 1 and 4-27. Wang et al. and Hoggatt et al. do not teach that the HDAd5/35++ also comprises the gene encoding SB100x (claims 3 and 4). Gonzalez et al. teach that using polycistronic vectors ensure the genes are delivered to and expressed in the same cell (see p. 8918). One of skill in the art would have found obvious to modify the method of Wang et al. and Hoggatt et al. by including the gene encoding SB100x into HDAd5/35++ with the reasonable expectation that doing so would result in HSPCs expressing enhanced [Symbol font/0x67]-globin gene levels.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
16. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633