DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/21/26 has been entered.
Claims 1-23 remain pending and under examination in this application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Those sections of Title 35, US code, not included in this action can be found in a previous office action. An action on the merits follows.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/21/26 is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statement has been considered by the examiner and an initialed and signed copy of the 1449 is attached to this action.
Claim Rejections - 35 USC § 103
The rejection of claims 1-4, 7-15, and 21-23 under 35 U.S.C. 103 as being unpatentable over Wang et al. (2008) Anal. Chem., Vol. 80, 2118-2124, in view of U.S. Patent 6,103,493 (2000), hereafter referred to as Skerra et al., Saviranta et al. (1998) Bioconjugate Chem., Vol. 9, 725-735, WO 2012/129514 (September, 2012), hereafter referred to as Riddell et al., Milone et al. (2009) Mol. Ther., Vol. 17 (8), 1453-11464. doi.org/10.1038/mt.2009.83, pages 1-20, and U.S. Patent 5,773,224 (1998), hereafter referred to as Grandics et al., is withdrawn in view of applicant’s amendments to the claims which now recite that the immunoaffinity bound CD4+ and CD8+ cells are simultaneously recovered in a single vessel.
The rejection of claims 5-6 and 16-20 under 35 U.S.C. 103 as being unpatentable over Wang et al. (2008) Anal. Chem., Vol. 80, 2118-2124, in view of U.S. Patent 6,103,493 (2000), hereafter referred to as Skerra et al., Saviranta et al. (1998) Bioconjugate Chem., Vol. 9, 725-735, WO 2012/129514 (September, 2012), hereafter referred to as Riddell et al., Milone et al. (2009) Mol. Ther., Vol. 17 (8), 1453-11464. doi.org/10.1038/mt.2009.83, pages 1-20, and U.S. Patent 5,773,224 (1998), hereafter referred to as Grandics et al., as applied to claims 1-4, 7-15, and 21-23 above, and further in view of Stemberger et al. (2012) PloS One, Vol. 7(4), e35798, pages 1-11, is withdrawn in view of applicant’s amendments to the claims which now recite that the immunoaffinity bound CD4+ and CD8+ cells are simultaneously recovered in a single vessel.
Claims 1-23 are newly rejected under 35 U.S.C. 103 as being unpatentable over WO 2012/129514 (September, 2012), hereafter referred to as Riddell et al., Milone et al. (2009) Mol. Ther., Vol. 17 (8), 1453-11464. doi.org/10.1038/mt.2009.83, pages 1-20, Philipovskiy et al. (2007) Infection and Immunity, Vol. 75(2), 878-885, Stemberger et al. (2012) PloS One, Vol. 7(4), e35798, pages 1-11, and U.S. Patent 5,773,224 (1998), hereafter referred to as Grandics et al.
Riddell et al. teaches compositions for adoptive immunotherapy of cancer comprising a combination of isolated CD4+ and CD8+ T cells (Riddell et al., pages 36-37). Riddell et al. teaches that the CD4 and CD8 cell populations were isolated from human peripheral blood mononuclear cells (PBMC), stimulated with anti-CD3 antibody, and transduced with lentivirus encoding a cancer specific chimeric antigen receptor (CAR) (Riddell et al., pages 30-33). Riddell et al. further teaches that the cells can be obtained from either healthy patients or patients with cancer (Riddell et al., page 34).
Milone et al. supplements Riddell et al. by teaching alternative methods of genetically modifying a combined population of CD4+ T cells and CD8+ T cells in which CD4+ T cells and CD8+ T cells are stimulated with alpha CD3/alphaCD28 aAPCs followed by transduction with a lentiviral vector encoding a gene of interest, where the genetically modified mixed population of CD4+ T cells and CD8+ T cells are cultured for at least 6 days (Milone et al., pages 2-3, 14 and Figures 1 and S1). In particular, Milone et al. teaches expressing a CAR in a mixed population of CD4 and CD8 T cells (Milone et al., pages 2-3). Milone et al. teaches substantial expansion of the transduced mixed population and anti-tumor activity in vitro and in vivo (Milone et al., pages 5-6).
Riddell et al. and Milone et al. differ from the instant methods by not teaching to simultaneously contact a composition comprising CD4+ and CD8+ T cells with first and second immunoaffinity reagents that specifically bind to CD4 and CD8 respectively, and further to simultaneously recover within a single vessel a combination of CD4+ and CD8+ T cells bound to the first and second immunoaffinity reagents. Philipovskiy et al. supplements the teachings of Riddell et al. and Milone et al. by teaching methods of simultaneous immunoaffinity tagging of a cell population comprising CD4+ and CD8+ T cells with two different immunoaffinity reagents and simultaneous recovery of CD4+ and CD8+ T cells using a magnetic bead separation column (Philipovskiy et al., pages 879-880). Specifically, Philipovskiy et al. teaches simultaneous isolation of CD4 and CD8 T cells from splenic cells where the splenic cells are simultaneously incubated with CD4 and CD8 microbeads followed by isolation of the bead bound cells using a magnetized LS column, washing of the magnetized column to remove non-bound cells, removal of the magnet and simultaneous collection of the CD4 and CD8 T cells, where the resulting isolated cells have a purity of greater than 90% (Philipovskiy t al., page 879). Philipovskiy et al. further demonstrates that the CD4 and CD8 T cells were active both in vitro and in vivo (Philipovskiy et al., pages 880-881). Therefore, based on the teachings and motivation provided by Philipovskiy et al. that a combined population of CD4 and CD8 T cells, which are functional both in vitro and in vivo, can be purified from a mixed primary cell composition using a methodology involving both the simultaneous labelling of the CD4 and CD8 T cells in the population with CD4 and CD8 magnetic microbeads followed by simultaneous isolation of the bound cells in a magnetized column and simultaneous recovery of the CD4 and CD8 cells from the column, it would have been prima facie obvious to the skilled artisan at the time of filing to isolate the combination of human CD4 and CD8 T cells used in the methods of genetically modifying a combination of CD4 and CD8 T cells to express a CAR as taught by Riddell and Milone et al. using the method taught by Philipovskiy et al. with a reasonable expectation of success.
Philipovskiy et al., while teaching the use of CD4 and CD8 magnetic beads to bind the CD4 and CD8 cells, does not specify the components of the CD4 and CD8 magnetic beads, such as the presence of biotinylated Fab fragments capable of forming a reversible bond with streptavidin functionalized magnetic microbeads. However, at the time of filing, Stemberger et al. teaches the components of antigen specific magnetic beads useful for magnetic column cell purification (Stemberger et al., pages 3, 4, and 80. For example, Stemberger et al. teaches a method for selection of cells expressing CD4 where the cells are first incubated with anti-CD4 Fab-strep-tag coated stret-Tactin functionalized magnetic beads, the bound cells are separated from non-bound cells in a column using a magnet, and the recovered cells released from the antibody-strep-tag -stret-Tactin magnetic beads using D-biotin (Stemberger et al., page 3). Stemberger et al. teaches that the advantage of this method which uses magnetic separation of reversibly bound strep-tag conjugated antibodies and strep-Tactin functionalized magnetic beads results in removal of the bead and spontaneous removal of the antibody marker resulting in extremely high levels of purity in the selected cells with over 90% and up to 98 or more percent purity (Stemberger et al, page 8, Figure 4D). Therefore, based on the benefits of the Fab-strep-tag- strep-Tactin-magnetic microbead approach taught by Stemberger et al., it would have been prima facie obvious to the skilled artisan at the time of filing to practice the methods of Philipovskiy et al. where the CD4 and CD8 magnetic microbeads comprise a biotinylated anti-CD4 or anti-CD8 Fab fragment reversibly bound to strep-Tactin magnetic microbeads according to Stemberger et al. in order to simultaneously generate a mixture of isolated human CD4+ and CD8+ T cells for use in the methods of Riddell et al. and Milone et al. with a reasonable expectation of success.
Finally, none of Riddell et al., Milone et al., Philipovskiy et al. or Stemberger et al. teach to use a closed system to isolate the CD4 and CD8 T cells. Grandics et al. provides motivation to set up and utilize a fully closed system comprising an immunoaffinity column by teaching that potential clinical use of cell separation systems requires a sterile, closed apparatus in which large quantities of viable, specific cell populations can be obtained rapidly from crude cell suspension or directly from blood (Grandics et al., columns 1 and 9). Therefore, based on the motivation to use a closed immunoaffinity column system to obtain cells for clinical use, it would have been prima facie obvious to the skilled artisan at the time of filing to modify the magnetic bead column isolation system taught by Philipovskiy et al. to be a closed system in order to provide a sterile sample of CD4 and CD8 cells for use in the cancer immunotherapy methods taught by Riddell et al. and Milone et al. with a reasonable expectation of success.
Double Patenting
The rejection of previously pending claims 1-23 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,400,115, hereafter referred to as the ‘115 patent, in view of Wang et al. (2008) Anal. Chem., Vol. 80, 2118-2124, and Stemberger et al. (2012) PloS One, Vol. 7(4), e35798, pages 1-11, is withdrawn in view of applicant’s amendments to the claims which now recite that the immunoaffinity bound CD4+ and CD8+ cells are simultaneously recovered in a single vessel. The ‘115 patent claims recite that the CD4+ selected and CD8+ selected cells are combined following selection at a specific ratio.
No claims are allowed.
Any inquiry concerning this communication from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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