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 .
The instant application is a CON of 16/092,870, now abandoned.
Claims 51-65 are examined in the instant application.
Claim Objections
Claim 51 is objected to because of the following informalities: Claim 51 recites “An improved method of genetically modifying CD34+ hematopoietic stem or progenitor cells”. However, claim 51 is objected to because it does not conform to the claim language required for an “improvement” claim as set forth in MPEP 1.75(e) (reproduced below). While claim 51 recites that the method is “improved” there is no limitation reciting what the improvement is. To overcome this objection is it suggested that Applicant incorporate claim language describing the improvement (see 1.75(e)(2)(3) below) or remove the “improved” limitation.
Appropriate correction is required.
MPEP 1.75(e):
Where the nature of the case admits, as in the case of an improvement, any independent claim should contain in the following order:
(1) A preamble comprising a general description of all the elements or steps of the claimed combination which are conventional or known,
(2) A phrase such as "wherein the improvement comprises," and
(3) Those elements, steps and/or relationships which constitute that portion of the claimed combination which the applicant considers as the new or improved portion.
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 63-65 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.
Claims 63-65 are unclear. Claims 63-65 depend from cancelled claim 1. Thus, it is not clear which claim, claims 63-65 depend from.
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 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.
Claims 51-55 and 57-63 are rejected and new claims 66-73 are rejected under 35 U.S.C. 103 as being unpatentable over Peled et al. (US 2007/0077652 A1, published 4/5/2007) in view of Raffi et al. (WO 2014/113415 A1, published 7/24/2014).
Claim Interpretation: while claim 63 is rejected under 112(b) above it is interpreted for the purposes of applying prior art that claim 63 depends from 51.
Regarding claim 51, Peled et al. teach a method of genetically modifying CD34+ HSPCs with an exogenous nucleic acid comprising co-culturing HSPCs with mesenchymal cells differentiated from endothelial cells (to serve as a feeder layer for HSPCs, pg. 7 parags. 75-76) and contacting the HSPCs with one or more exogenous nucleic acid molecules (pg. 3 parags. 23 and 25, pg. 4 parag. 28, pg. 6 parag. 73, pg. 25 parag. 411, pg. 26 parag. 419).
Regarding claim 52, Peled teaches the stem cells are derived from peripheral blood, bone-marrow or umbilical cord blood (pg. 4 parag. 44).
Peled teaches the cells can be of human origin (pg. 3 parag. 22).
Regarding claims 57 and 58, Peled teaches that exogenous nucleic acid can be introduced via liposome-mediated transfection (pg. 25 parag. 414 and pg. 26 parag. 428).
Regarding claim 59, Peled teaches that the HSPCs are transduced with a retroviral vector (parags. 414, 415 and 437).
Regarding claim 61, Peled teaches that the exogenous nucleic acid is in a plasmid vector (pg. 26 parag. 426 and pg. 27 parag. 435).
Regarding claims 60 and 62, Peled teaches that transduction can be done with a retroviral vector (pg. 25 parags. 403/414 and pg. 28 parag. 437).
Regarding claim 63, Peled teaches co-culturing prior transduction of HSPCs (parag. 2).
Regarding claims 69 and 73, Peled teaches co-culturing for at least 21 days to expand cells (parag. 68) and then transducing expanded stem cells (parag. 28).
Peled does not teach:
E4ORF1+ endothelial cells and human umbilical vein endothelial cells (HUVECs).
(i) Regarding E4ORF1+ endothelial cells in claim 51 and HUVECs in claims 53-55, Raffi et al. teach transforming HUVECs with an adenovirus expressing the E4ORF1 gene (pg. 36 lines 14-16) to serve as a feeder layer in a method of producing CD34+ HSPCs (pg. 3 parag. 11).
Specifically, Raffi teaches on pg. 17:
“[0048] Feeder cells are preferably able to grow and survive in a serum-free environment to enable culturing with ECs in serum-free media. Many types of endothelial cells cannot be maintained in culture in the absence of serum. Modification of endothelial cells to enable survival and proliferation for use as feeder cells in a serum-free culture can overcome this barrier in endothelial cells that would otherwise require serum.
[0049] Endothelial cells can be modified, for example, by transformation of cells with genes that drive growth and proliferation in the absence of serum. Examples of genes that support survival of endothelial cells in culture without serum include the Akt (protein kinase B or PKB) gene and the adenovirus E40RF1 gene. In a specific embodiment, HUVECs are transformed to express a gene selected from Akt or the adenovirus E40RF1 gene.”
Raffi contines to teach that co-culturing can be commenced after genetic modification of transduced cells (pg. 4 parag. 14).
Raffi continues to teach that using E4ORF1+ HUVECs as a feeder platform significantly increased the yield and persistence of hematopoietic-like colonies and is beneficial for hematopoietic reprogramming (pg. 24 parags. 71-73).
Thus, at the time of filing it would have been prima facie obvious to combine the teachings of Peled regarding a method of genetically modifying CD34+ HSPCs with an exogenous nucleic acid comprising co-culturing HSPCs with mesenchymal cells differentiated from endothelial cells with the teachings of Raffi regarding the advantages of using E4ORF1+ HUVECs as a feeder layer for hematopoietic progenitor cells to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to substitute the E4ORF1+ HUVECs of Raffi for the endothelial-derived mesenchymal cells of Peled since Raffi teaches that E4ORF1+ HUVECs as a feeder platform significantly increased the yield and persistence of hematopoietic-like colonies and is beneficial for hematopoietic reprogramming. Since Peled is drawn to genetically modifying CD34+ hematopoietic stem cells, it would be obvious to substitute the E4ORF1+ HUVECs of Raffi since they offer advantages for hematopoietic reprogramming (a type of genetic modification).
There would have been a reasonable expectation of success that the E4ORF1+ HUVECs of Raffi would function in the method of Peled since Raffi teaches obtaining CD34+ HSPCs using their method of co-culture (see claim 13 of Raffi for example).
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim 56 is rejected under 35 U.S.C. 103 as being unpatentable over Peled et al. (US 2007/0077652 A1, published 4/5/2007) in view of Raffi et al. (WO 2014/113415 A1, published 7/24/2014) as applied to claims 51-55 and 57-63 above, and further in view of Llames et al. (ePub 3/23/2015, Tissue Engineering: Part B, Vol. 21(4), pgs. 345-353).
Peled and Raffi are relied upon above in teaching a method of genetically modifying CD34+ HSPCs.
Peled and Raffi do not teach:
(i) mitotically inactivated endothelial cells.
Claim Interpretation: the specification does not recite the term “mitotically inactivated”, however it is interpreted that the irradiation taught by Llames would mitotically inactivate the endothelial cells of the claimed invention.
(i) Regarding mitotically inactivated endothelial cells, Llames et al. teach “feeder layer cells usually consist of adherent growth arrested, but viable and bioactive, cells. These cells are used as a substratum to condition the medium on which other cells, particularly at low or clonal density, are grown. Often the cells of the feeder layer are irradiated or otherwise treated so that they will not proliferate.” (pg. 345 col. 1 lines 1-6).
Llames continues to teach that with regard to stem cells such as human ES cells, it is necessary for the feeder layer to be mitotically inactive to support the growth and proliferation human ES cells (pg. 348 col. 2 parag. 5).
Thus at the time of filing it would have been prima facie obvious to combine the teachings of Peled and Raffi regarding a method of genetically modifying CD34+ HSPCs with the teachings of Llames regarding mitotically inactivated feeder cells to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to mitotically inactivate the E4ORF1+ feeder cells of Raffi since this would prevent the proliferation of E4ORF1+ feeder cells and permit the growth and proliferation of the CD34+ HSPCs of Peled.
There would have been a reasonable expectation of success that the E4ORF1+ HUVECs of Raffi could be mitotically inactivated since Llames teaches that irradiation can be used to mitotically inactivate feeder cells while still permitting their use as growth platform (i.e. feeder cell).
Thus, the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claims 64 and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Peled et al. (US 2007/0077652 A1, published 4/5/2007) in view of Raffi et al. (WO 2014/113415 A1, published 7/24/2014) as applied to claims 51-55 and 57-63 above, and further in view of Yildirim et al. (2005, Bone Marrow Transplantation, Vol. 36, pgs. 71-79).
Claim Interpretation: while claims 64 and 65 are rejected under 112(b) above it is interpreted for the purposes of applying prior art that claims 64 an 65 depend from 51.
Peled and Raffi are relied upon above in teaching a method of genetically modifying CD34+ HSPCs.
Peled and Raffi do not teach:
an increase of CD34+ HSPCs generation.
(i) Regarding an increased percentage of genetically modified CD34+ HSPCs, Yildirim et al. teaches that co-culturing CD34+ HSPCs with HUVECs results in superior expansion compared to even cytokine-supplemented cultures (see Abstract, Introduction and Figs. 2-4, particularly Fig. 4).
Thus, at the time of filing it would have been prima facie obvious to combine the teachings of Peled regarding a method of genetically modifying CD34+ HSPCs with an exogenous nucleic acid comprising co-culturing HSPCs with mesenchymal cells differentiated from endothelial cells with the teachings of Raffi regarding the advantages of using E4ORF1+ HUVECs as a feeder layer for hematopoietic progenitor cells and with the teachings of Yildirim regarding the advantages of co-culturing CD34+ HSPCs with HUVECs to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated by Yildirim to co-culture the CD34+ HSPCs of Peled with HUVECs since Yildirim teaches that co-culturing the CD34+ HSPCs with HUVECs results in an increased generation of CD34+ HSPCs. Thus, the skilled artisan would find it obvious that if there is increased generation of CD34+ HSPCs, then there are more cells which can be genetically modified, thus increasing the percentage of genetically modified CD34+ HSPCs as claimed.
Yildirim provides a reasonable expectation of success that the CD34+ HSPCs of Peled would have increased generation since Yildirim teaches that co-culture of CD34+ HSPCs with HUVECS results in increased proliferation (see pg. 75 col. 2 parag. 1 of Yildirim for example).
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
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