DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment, filed 01/30/2024, has been entered.
Claims 12-13 have been canceled.
Claims 1-11 and 14-26 are pending.
Election/Restrictions
Applicant’s election of Group I and species of porcine cell comprising a reduced level of B3GNT5 activity in the reply filed on 06/15/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 4-6, 10-11, 14-16, 20-26 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
Claims 1-3, 7-9, 17-19 are currently under examination as they read on a genetically modified porcine cell comprising a reduced level of B3GNT5 activity.
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.
Claims 1-3, 7-9, 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Estrada et al. (Xenotransplantation 2015 22:194-202) in view of Alam et al. (Sci Rep 7, 45367 (2017); cited in IDS), Byrne et al. (Xenotransplantation 2018 25:e12394) and Ouyang et al. (Biochem Genet 2012 50:19-33).
Estrada teaches genetically modified porcine cells for xenotransplantation in which glycosyltransferase genes responsible for synthesis of xenogeneic carbohydrate antigens are inactivated to reduce antibody binding and improve xenograft compatibility (See entire document, in particular, see Results). Estrada further teaches genetically engineered porcine organs suitable for transplantation (Introduction and Discussion).
Byrne teaches that glycosyltransferase-mediated glycans expressed on porcine glycoproteins and glycosphingolipids are targets of xenoreactive antibodies and that eliminating the glycosyltransferases responsible for producing these glycans is an effective strategy for reducing xenoantigenicity (see entire document, in particular, see Conclusion).
Alam teaches targeted disruption of the B3GNT5 gene and demonstrates that loss of B3GNT5 results in reduced synthesis of lacto- and neolacto-series glycosphingolipids, thereby producing cells with reduced or absent B3GNT5 activity (see entire document).
Ouyang teaches the porcine B3GNT5 gene and characterizes polymorphisms within the porcine B3GNT coding sequence, thereby evidencing the existence and characterization of B3GNT5 in swine before the effective filing date of the claimed invention (see entire document).
Regarding claims 1 and 2, although Estrada does not teach modifying B3GNT5 gene in porcine cell, it would have been obvious to one of ordinary skill in the art to modify the porcine BeGNT5 gene identified by Ouyang using the B3GNT5 disruption techniques taught by Alam in the genetically engineered porcine cells of Estrada. Estrada and Byrne teach that eliminating glycoysyltransferase-mediated glycan antigens reduces xenogenic immune recognition, while Alam teaches that B3GNT5 is responsible for synthesis of lacto- and neolacto-series glycosphingolipids. Thus, one of ordinary skill in the art would have been motivated to disrupt B3GNT5 in porcine cells as another glycoengineered strategy to reduce xenogenic glycan antigens and improve xenotransplant compatibility.
Regarding claim 3, the combined teachings of Estrada, Byrne and Alam render obvious the claimed genetically modified porcine cell. Because disruption of B3GNT5 predictably reduces B3GNT5-dependent glycan epitopes that serve as targets for xenoreactive antibodies, the modified porcine cell would inherently exhibit reduced binding of human immunoglobulins relative to an unmodified porcine cell.
Regarding Claim 7-9 and 17-19, Estrada teaches that the glycosyltransferase gene is functional in transplantable organs such as kidney, heart, liver, lung and pancreas genetically modified porcine cells derived from liver (see Discussion) and therefore, the genetically modified porcine cells may be obtained from these transplantable tissues and organs. Accordingly, it would have been obvious to obtain tissues and organs comprising the genetically modified porcine cells of claims 1 and 2 for the purpose of transplantation.
One of ordinary sill in the art would have been motivated to combine the teachings of Estrada, Byrne, Alam and Ouyang because each reference is directed to reducing glycan-mediated xenogeneic immune recognition through genetic modification or porcine cells. Applying the known B3GNT5 gene disruption taught by Alam to the porcine B3gnt5 gene identified by Ouyang in the xenotransplantation context of Estrada and Byrne would have been predicable use of known genome-editing techniques to reduce glycan antigen expression and improve xenograft compatibility.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention as evidence by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/SHARON X WEN/Primary Examiner, Art Unit 1641
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