Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8-31-26 has been entered.
Claims 1-25 have been canceled. Claims 26-46 are pending and under consideration.
Applicant's arguments filed 8-31-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
When referencing the specification, please use page and paragraph number (and line number as necessary) of the original specification. Do not simply use paragraph numbers or refer to the US Patent Application Publication.
Specification
The word “apoptosis” was added to the sentence “SV40 large T antigen prevents cMyc-induced in murine fibroblasts” on pg 11, para 35, line 2, in the amendment filed 2-25-26.
Claim Rejections - 35 USC § 112
Written Description
Claims 26-46 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Withdrawn rejections
The rejection regarding using one or more non-viral episomal vectors encoding Oct4, Sox2, and SV40 T antigen as required in claims 26, 42, or 46 has been withdrawn. Fig. 2C, Fig. 4, Table 2 (pg 16-17), Table 3 (pg 18-21), and Fig. 5A and 5B (described on pg 5) are limited to one vector, but the sentence bridging pg 7-8 describes using one or more than one vector to encode Oct4, Sox2 and SV40 T antigen as broadly encompassed by claims 26, 42, 46.
The rejection regarding a somatic cell comprising one or more non-viral episomal vectors encoding Oct4 and Sox2 and SV40 T antigen, wherein the cell is “fetal or post-natal primate cells” as required in claim 27 has been withdrawn in view of pg 4, para 11, last 4 lines on pg 7 which says the starting cell type for making pluripotent cells are somatic cells from a fetal or post-natal individual.
The rejection regarding a somatic cell comprising an episomal vector encoding, in order, a 1st promoter, Oct4, IRES2, Sox2, 2nd promoter, Myc, IRES2, KLF4, a 3rd promoter, NANOG, IRES2, LIN28 as required in claim 34 has been withdrawn in view of the amendment.
The rejection regarding the somatic cell comprising an episomal vector encoding, in order, a 1st promoter, Oct4, IRES2, Sox2, 2nd promoter, SV40 T antigen, IRES2, KLF4 and an episomal vector encoding, in order, a 1st promoter, Oct4, IRES2, Sox2, 2nd promoter, Myc, IRES2, KLF4, a 3rd promoter, NANOG, IRES2, LIN28 in claim 35 has been withdrawn in view of the amendment.
The rejection regarding a somatic cell comprising an episomal vector encoding, in order, a 1st promoter, Oct4, IRES2, Sox2, 2nd promoter, SV40 T antigen, IRES2, KLF4, an episomal vector encoding, in order, a 3rd promoter, Oct4, IRES2, Sox2, 4th promoter, NANOG, IRES2, and KLF4, and an episomal vector encoding a 5th promoter, Myc, IRES2, KLF4, LIN28 in claim 37 has been withdrawn in view of the amendment.
The rejection regarding a somatic cell comprising an episomal vector encoding, in order, a 1st promoter, Oct4, IRES2, Sox2, 2nd promoter, NANOG, IRES2, LIN28, an episomal vector encoding, in order, a 3rd promoter, Oct4, IRES2, Sox2, 4th promoter, SV40 T antigen, IRES2, KLF4, and an episomal vector encoding a 5th promoter, OCT4, IRES2, Sox2, a 6th promoter, Myc, IRES2, KLF4 in claim 39 has been withdrawn in view of the amendment.
The rejection regarding exposing somatic cells to Oct4, Sox2, and SV40 T-antigen by any means as broadly encompassed by claim 46 has been withdrawn in view of the amendment.
The rejection regarding obtaining any “reprogrammed cells having a higher potency level than the primary somatic cells” as required in claim 46 has been withdrawn in view of the amendment.
Indefiniteness
The rejection of claims 26-46 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn in view of the amendment. The rejections of claims 26 and 46 have been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 103
A) Claims 26-28, 30, 32, 40-46 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mack (20100003757) in view of Hermeking (PNAS, 1994, Vol. 91, pg 10412-10416).
Mack transfected isolated primate somatic cells with a single plasmid encoding multiple reprogramming factors including Oct4 and Sox2 such that pluripotent cells were obtained (paragraphs 6; 17; 20; 23; 32; 141, lines 1-7; 159, lines 1-6 and lines 11-13; para 225). The cells were differentiated into various somatic cells (para 209-210). The plasmid of Mack (para 228; “Use of a residue-free reprogramming plasmid”) are episomal as encompassed by claim 26 and 42 because applicants taught plasmids were unstable episomal vectors that cannot replicate their DNA (paragraph 27).
Mack did not teach the cells comprised SV40 T antigen as required in claims 26 and 42.
However, Hermeking taught SV40 T antigen prevented cMyc-induced apoptosis (abstract) and Hanna taught SV40 T antigen enhanced reprogramming efficiency (abstract).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make isolated primary somatic cells comprising a non-viral episomal vector encoding Oct4 and Sox2 as described by Mack and add a vector encoding SV40 T antigen as described by Hermeking and Hanna. Those of ordinary skill in the art at the time of filing would have been motivated to do so to prevent cMyc-induced apoptosis as described by Hermeking or improve reprogramming as described by Hanna.
The limitation cells “obtained from fetal or post-natal primate individuals” as required in claim 27 is a product-by-process limitation buried in a method claim. The claim does not clearly set forth an active step of isolating fetal or post-natal cells or an active step of fetal or post-natal cells; therefore, the steps do not have to occur. All cells are ultimately obtained from a fetal or post-natal primate because adult cells are derived from fetal or post-natal cells. Therefore, the concept of cells “obtained from fetal or post-natal primate individuals” in claim 27 encompasses any cell because all cells are ultimately derived from fetal or post-natal cells. In other words, the phrase “obtained from fetal or post-natal primate individuals” bears no patentable weight because it does not distinguish the cells of Mack (ultimately obtained from fetal or post-natal cells) from those claimed.
Mack taught the pluripotent cells were human as required in claim 28.
Mack taught the pluripotent cells in culture media as required in claims 40, 42, and 44.
Culturing the cells 18 days as required in claims 41 and 45 was obvious in view of Mack who taught culturing for 14 days. Those of ordinary skill in the art at the time of filing would have been motivated to extend culture to 18 days to obtain more cells.
The cells must “transiently express SV40 T antigen” as required in claim 43 because a plasmid was used to express SV40 T antigen.
Claim 46 has been included for reasons set forth above regarding claim 26 and 42.
Response to arguments
Applicants argue Hermeking is limited to using growth factor- or serum-starved cells and point out the claims do not require growth factor- or serum-starved cells. Applicants’ argument is not persuasive because Hermeking concluded that SV40 T antigen prevented cMyc-induced apoptosis. Furthermore, the claims encompass using growth factor- or serum-starved cells.
B) Claims 29, 31 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mack (20100003757) in view of Hermeking (PNAS, 1994, Vol. 91, pg 10412-10416) as applied to claims 26-28, 30, 32, 40-46 and further in view of Takahashi (Cell, 2007, Vol. 131, pg 861-872), and Yu (Science, 2007, Vol. 318, pg 1917-1920).
The combined teachings of Mack and Hermeking taught transfecting isolated primate somatic cells with a single plasmid encoding multiple reprogramming factors including Oct4, Sox2, SV40 T-antigen and optionally Lin28, Nanog, Myc, KLf4 such that pluripotent cells were obtained.
The combined teachings of Mack and Hermeking did not teach Oct4 and Sox2 and Lin28, Nanog, Myc, or Klf4 were human as required in claims 29 and 31.
However, Yu used cDNA encoding human Oct4, Sox2, Nanog and Lin28 (pg 3, “Lentiviral transduction…” in the Supplementary information), and Takahashi (2007) used human Oct4, Sox2, Klf4 and cMyc (pg 869, col. 2, plasmid construction).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to transfect somatic cells with a plasmid encoding Oct4 and Sox2 as described by Mack using human Oct4 and Sox2 as described by Takahashi and Yu. Those of ordinary skill in the art at the time of filing would have been motivated to use human Oct4 and Sox2 because the cells are also humans.
Response to arguments
Applicants argue the rejection must be dropped because rejection A) is faulty. Applicants’ argument is not persuasive for reasons set forth above.
C) Claims 33-39 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mack (20100003757) in view of Hermeking (PNAS, 1994, Vol. 91, pg 10412-10416) as applied to claims 26-28, 30, 32, 40-46 and further in view of Takahashi (Cell, 2006, Vol. 126, pg 663-676), Takahashi (Cell, 2007, Vol. 131, pg 861-872), and Yu (Science, 2007, Vol. 318, pg 1917-1920).
The combined teachings of Mack and Hermeking taught transfecting isolated primate somatic cells with a single plasmid encoding multiple reprogramming factors including Oct4, Sox2, SV40 T-antigen and optionally Lin28, Nanog, Myc, KLf4 such that pluripotent cells were obtained.
The combined teachings of Mack and Hermeking did not teach the vector components in the order as written in claims 33-39.
However, all of the components were described by the combined teachings of Mack, Hermeking, Yu, Takahashi (2006), and Takahashi (2007). The order in which they are set forth in claims 33, 34, 35, 37, 39 was simply a matter of design choice because the order was variable as shown by Mack, Yu, Takahashi (2006), and Takahashi (2007). Those of ordinary skill in the art at the time of filing would have been motivated to arrive at the claimed structures to functionally express the desired proteins in a reasonable number of vectors.
Claims 36 and 38 require the promoter is an EF1α or CMV promoter which is taught by Mack (para 50, 224; Fig. 4).
Response to arguments
Applicants argue the rejection must be dropped because rejection A) is faulty. Applicants’ argument is not persuasive for reasons set forth above.
Double Patenting
The rejection of claims 21-25 on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10106772, 9499786, 8440461, and 8183038 has been withdrawn.
The claims of 10106772 are drawn to:
A method of reprogramming human somatic cells, the method comprising the steps of:
introducing a non-integrating vector encoding Oct-4 and Sox2 and at least one of Nanog and Lin28 operably linked to one or more heterologous promoters into isolated human somatic cells; and culturing the somatic cells under embryonic stem (ES) cell culture conditions such that pluripotent reprogrammed cells are obtained.
The claims of 9499786 are drawn to:
1. An enriched population of human pluripotent cells having a normal karyotype, wherein the human pluripotent cells comprise the genome of a single somatic cell of a postnatal individual human and further comprise an integrated non-native polynucleotide sequence encoding potency-determining factors comprising Oct-4 and Sox2.
2. The population of claim 1, wherein the potency-determining factors additionally comprise at least one of Nanog or Lin28.
The claims of 8440461 drawn to:
A method of reprogramming primate somatic cells, the method comprising the steps of: introducing a retroviral vector encoding a plurality of potency-determining factors into the primate somatic cells under conditions sufficient to reprogram the cells, wherein the potency-determining factors comprise Oct-4 and Sox2, and do not comprise c-Myc and Klf4; and culturing the primate somatic cells under embryonic stem cell culture conditions to obtain pluripotent reprogrammed cells. (Claim 1 of Parent application 12/053440 now US patent 8440461)
Claim 1 of 8183038 is drawn to:
1. A composition comprising recombinant nucleic acid encoding potency-determining factors SOX2, OCT-4, NANOG, and LIN28, the factor-encoding nucleic acid being operably linked to at least one heterologous promoter, wherein the composition induces reprogramming when introduced into a mammalian cell.
10106772, 9499786, 8440461, and 8183038 did not teach somatic cells containing a non-viral episomal vector encoding Oct4 and Sox2 and SV40 T antigen as required in claims 26, 44, 46.
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
