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 .
Election/Restrictions
Applicant's election with traverse of Group I, and species SEQ ID NO: 27 and SEQ ID NO: 28 in the reply filed on 2/27/2026 is acknowledged. The traversal is on the ground(s) that the cited reference, De Boer is a different technology, and the engineered protein is not on a cell membrane. The amendment filed on 2/27/2026 also changes the dependency of claim 60 to claim 55. As such, the restriction required has been revisited.
Based on the amendment, the technical feature that links the invention of I and II is an engager cell that comprises an engager molecule on a cell surface that engages with a SIRPα, wherein the cell may be CAR cell, T cell, NK cell, an endothelial cell, a dopaminergic neuron, a cardiac cell, a pancreatic islet cell or a retinal pigment endothelium cell. This technical feature does not make a contribution over prior art based on the teaching from Shrestha (Transplantation, September 2020, Vol.104 (53), p S11). Shrestha teaches an islet cell that displays SA-CD47 on the surface (abstract). Since CD47 is the ligand of SIRPα, it meets the limitation of engager molecule. Therefore, this technical feature cannot link the invention as a whole to form a single general inventive concept under PCT Rule 13.1.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claim 60 and 65-66 are withdrawn from consideration for being directed to non-elected subject matter. Claims 1, 4, 7, 15, 19, 22, 24, 33, 39, 40, 43, 45-49, 55 and 58 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/19/2026 have been considered by the examiner.
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 19 and 28 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.
Regarding claim 19, the word “heterologous” renders the claim indefinite because it is unclear what this transmembrane (TMD) domain is heterologous to in the context of claim 1. Does it mean it is heterologous to the cell, the nonfunctional intracellular domain (ICD) or other components of the cell.
Regarding claim 28, the recitation of “connecting ECD, TMD or ICD sequences” renders the claim indefinite because it is unclear what the linker or hinge connects ECD, TMD or ICD to. Does it mean they are connected to each other, the cell or other molecules?
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1, 4, 7, 15, 19, 22, 24, 33, 39, 40, 43, 45-49, 55 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The term “cell” as defined by the specification in paragraph [0174]-[0182] the cell is present or intended to be present in a human being, said cell becoming integrated into the human being and therefore being an inseparable part of the human itself. The scope of the claim, therefore, encompasses a human being, which is non-statutory subject matter. As such, the recitation of the limitation “an isolated” would be remedial. See 1077 O.G. 24, April 21, 1987.
Claim 1, 55 and 58 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature based product without significantly more. The claim(s) recite(s) a SIRPα engager cell that comprises a cell surface engager that engages with SIRPα, wherein the engager lacks a functional CD47 intracellular domain. Besides CD47, human surfactants protein A and protein D are also known ligands that engages SIRPα, they are expressed on mucosal surfaces such as pulmonary mucosa and urogenital tract, which are endothelial cells (Feng et al. European Journal of Immunology, 2023, Vol.3, pages 1-13, see page 3, 1st col., 2nd paragraph). This judicial exception is not integrated into a practical application because there is no further limitation for application of said cells. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there is no additional elements recited. Isolating said cell from its natural environment (claim 58) does not add any element that is considered significantly more than the judicial exception. Therefore, the claimed cell of claims 1, 55 and 58 are not patent eligible.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4, 24, 28, 48, 55 and 58 is/are rejected under 35 U.S.C. 102 (a1) as being anticipated by Shrestha et al (cited above).
Claim 1 is drawn to a SIRPα engager cell, comprising a cell surface engager molecule that engages a SIRPα protein on an immune cell, wherein said engagement prevents said engager cell being killed by said immune cell, and said engager lacks a functional CD47 ICD.
Shrestha et al teaches constructing a synthetic gene containing the extracellular domain of mouse CD47 C terminus fused to the core of streptavidin (SA)-CD47, where said SA-CD47 is transiently displayed on the surface of biotinylated cells and islets. Shrestha et al. teaches SA-CD47 engineered cell showed enhanced engraftment, and reduced instant blood mediated inflammatory reaction (IBMIR). Since CD47 is known to interact with innate immune cells, it meets the limitation of SIRPα engage molecule. Therefore, the teaching from Shrestha meets the limitation of claim 1, 4, 24 (does not have intracellular domain), claim 48 (all cells are differentiated from a pluripotent cell) and claim 55.
Regarding claim 28, since the specification does not provide a definition for “linker” and “hinge,” and it is unclear where ECD is connecting to, the SA-biotin connection taught by Shrestha is considered to meet the limitation.
Regarding claim 58, the islet cell transplantation would inherently comprising saline or medium to keep islet cell function, which meets the limitation of pharmaceutical carrier.
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.
Claim(s) 39, 40, 43, 45 and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shresta, in view Schrepfer (US2020/0354684).
The teaching from Shresta has been discussed above.
However, Shresta does not teach the SIRP engager cell further comprising a reduced or eliminated HLA-I or HLA-II expression and/or reduced or eliminated ABO blood group antigen A1, A2 or B (39).
Schrepfer teaches blood type O RH- hypo-immunogenic pluripotent stem cells (HIPO-) (title). Schrepfer teaches such cells can evade rejection by the host allogeneic immune system and avoid blood antigen type rejection (paragraph [0013]). Schrepfer teaches the HIPO- cells comprises reduced HLA-I and HLA-II expression, increased CD47 expression, and a universal blood group O Rho- blood type (paragraph [0013]).
It would have been obvious to an ordinary skilled in the art that regenerative cell therapy requires low immunogenicity from the host when the cells are transplanted into said host based on combined teaching from Shresta and Schrepfer. The ordinary skilled in the art would recognize that expressing CD47 extracellular domain on the cell surface is sufficient for evading innate immune cytotoxicity as demonstrated by Shresta. The ordinary skilled in the art would have been motivated to use the same strategy to other types of cell, such as blood cell taught by Schrepfer, to enable blood cell transfusion. Replacing one type of cell with another for displaying CD47 on cell surface would have been within the capability of an ordinary skilled in the art. Therefore, the claimed invention of claims 39, 40, 43, 45 and 49 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 46 and 47 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shresta, in view of Sablik et al. (Transplant immunology, 2019, Vol.54, pages 52-58).
The teaching from Shresta has been discussed above. However, Shresta does not teach the cell further comprising elevated expression of an antibody Fc receptor on the cell surface, where said Fc receptor helps to evade antibody dependent cellular cytotoxicity (ADCC), such as CD16.
Sablik teaches increased CD16 expression on NK cells is indicative of antibody-dependent cell mediated cytotoxicity (ADCC) in chronic antibody mediated rejection that lead to graft failure (title and abstract).
It would have been obvious to an ordinary skilled in the art that the cell taught by Shresta has reduced innate immunity that contributes to instant blood mediated inflammatory reaction by displaying engineered CD47 on its cell surface. The ordinary skilled in the art would recognize that reducing CD16 expression on NK cell would receive the benefit of reduce antibody mediated rejection that can also lead to graft failure based on the teaching from Sablik. The ordinary skilled in the art would be motivated to further engineer the cell to express an antibody Fc receptor that targets CD16 so that ADCC would also be reduced following transplantation. Therefore, the claimed invention of claims 46 and 47 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 1, 4, 7 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Criag (US 2010/02395709), in view of Horlick (The Journal of Biological Chemistry, 2013, Vol.288, no. 27, pages 19861-19869).
Criag teaches fusion peptides that comprises CD47 extracellular domain and variants thereof fused to a moiety capable of multimer formation such as Fc polypeptide (paragraph [0047]). Criag teaches said fusion polypeptide may be used to alter immune-responsiveness of an immune cell through interaction with SIRPα (paragraph [0054]). Criag teaches the fusion protein may be linked by linker or spacer (paragraph [0133]). Criag teaches recombinant construct that may be used for expressing said fusion polypeptide in suitable host cells such as COS, CHO or HEK293 cells (paragraph [0151]).
However, Criag does not teach the fusion polypeptide is expressed on cell surface.
Horlick teaches a method of simultaneous surface display and secretion of proteins from mammalian cells facilitate efficient in vitro selection and maturation of antibodies. Horlick teaches a method of presentation of both secretion and surface presentation of Fab (Figure 2 and legend).
It would have been obvious to an ordinary skilled in the art that the fusion polypeptide taught by Criag may be produced in host cell with both surface presentation and secretion as taught by Horlick. The ordinary skilled in the art would have been motivated to do so to receive the benefit of efficient selection as taught by Horlick. Therefore, the claimed invention of claim 1 and 2 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 7, Criag teaches CD47 is fused to Fc portion of IgG.
Regarding claim 19, Horlick teaches transmembrane domain of IgG that may be used (Figure 2A and legend).
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Criag and Horlick, as applied to claims 1 and 7 above, and further in view of sequence BDL39563 disclosed in WO2016205042.
The teaching from Criag and Horlick has been discussed above.
However, neither reference teaches the antibody comprises SEQ ID NO: 5.
Sequence BDL39563 from ‘042 application has 100% sequence homology with SEQ ID NO: 5, and is part of SIRPα agonist antibody (see alignment).
It would have been obvious to an ordinary skilled in the art to use prior art known sequence from an antibody when constructing a fusion SIRPα engager molecule that rendered obvious by Criag and Horlick Therefore, the claimed invention of claim 13 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Criag and Horlick, as applied to claim 1 and 19 above, and further in view of sequence BGW40808 disclosed in WO2019199941.
The teaching from Criag and Horlick has been discussed above.
However, neither reference teaches the fusion protein comprises the sequence SEQ ID NO: 27.
BGW40808 has 100% sequence homology with SEQ ID NO: 27, and is the transmembrane domain for PDGFR transmembrane domain.
It would have been obvious to an ordinary skilled in the art to use prior art known sequence encoding transmembrane domain when constructing a fusion SIRPα engager molecule that rendered obvious by Criag and Horlick. The transmembrane domain serves to anchor the antibody or fragment thereof to the cell surface, which does not need to be homologous to the antibody. Therefore, the claimed invention of claim 22 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1, 4, 7, 15, 19, 22, 24, 33, 39, 40, 43, 45-49, 55 and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-38 of copending Application No. 19528505 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the hypoimmunogenic cells claimed in claims 1-38 encodes a SIRPα engager, which anticipates the cells claimed in present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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/CELINE X QIAN/Primary Examiner, Art Unit 1637
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