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 .
Detailed Action
This action is in response to the papers filed July 8, 2026.
Claim Amendments
Applicant’s amendment to the claims filed on 07/08/2026 is acknowledged.
Claims 18-19 have been cancelled.
Claims 16 and 20 are amended.
Claims 1-17, 20-21 are pending.
Claims 1-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claims 16-17, 20-21 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See the Requirement for Restriction/Election mailed 01/30/2025.
Applicant elected with traverse Invention II, drawn to a composition for preparing donor tissue for transplantation, in the reply filed 02/28/2025.
Accordingly, claims 1-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 02/28/2025.
Priority
The instant application 17/807,436 was filed on 06/17/2022. This application is a continuation (CON) of U.S. Application No. 16/568,628 filed 09/12/2019, claiming priority based on U.S. Provisional Application 62/730,735 filed 09/13/2018.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 03/19/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. Applicant’s remarks filed 07/08/2026 have been carefully considered, but the arguments are not moot in view of the new grounds of rejection or otherwise sufficiently addressed in the previous Office action.
Claim Rejections - 35 USC § 103
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 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Xiaofeng et al. (2010) “AAV based gene delivery to myocardium in rodents and pigs” Xenotransplantation, 17(2), 111; in view of Buermann et al. (15 Feb 2018) “Pigs expressing the human inhibitory ligand PD‐L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties” Xenotransplantation, 25(5), e12387, 15 pages; and Faust et al. (2013) “CpG-depleted adeno-associated virus vectors evade immune detection” The Journal of clinical investigation, 123(7), 2994-3001.
This rejection is newly applied, necessitated by amendment.
Xiaofeng discloses a donor heart for transplantation comprising a recombinant associated viral (AAV) vector comprising a nucleic acid encoding human PD-L1 (hPD-L1). See entire disclosure.
The donor heart is perfused with cardioplegic solution or an in situ-Langendorff perfusion system. See Methods. Since the donor hearts are perfused with a solution having a composition which preserves the donor hearts until transplantation occurs, Xiaofeng is found to teach or fairly suggest the limitation of “an organ preservation solution comprising one or more preservatives,” as instantly claimed in claim 16.
Xiaofeng reports that “hPD-L1 transduction resulted in no significant difference of survival time and signs of rejection after allogeneic rat heart transplantation” (first paragraph of Results), and “[g]ene transfer of hPD-L1 was ineffective to protect against allorejection, [and] on the contrary there was a trend to aggravated rejection” (last paragraph of Conclusions).
"[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). See, MPEP 2144.01.
In this case, the lack of protective effects of hPD-L1 expression observed by Xiaofeng in their allogeneic transplantation model was due to “species incompatibility” (second paragraph of Results, and second paragraph of Conclusions). In other words, since Xiaofeng performed pig-to-pig transplantation, species incompatibility between human PD-L1 (hPD-L1) and the porcine immune system did not lead to the protective effects of human PD-L1 overexpression that would have been expected in pig-to-human transplantation, i.e., in the situation where the porcine donor heart overexpressing human PD-L1 is introduced into a human subject having a human immune system. The results in Xiaofeng were acceptable because the objective of the study was “[t]o optimize transgene [hPD-L1] expression levels after AAV-mediated gene transfer” (first paragraph), and Xiaofeng concludes that double transgenic pig hearts may be efficiently transduced with hPD-L1 to “further optimize long-term survival after pig-to-primate cardiac xenotransplantation” (last paragraph of Conclusions). Therefore, Xiaofeng teaches or fairly suggests that recombinant human PD-L1 expression would have been beneficial for inducing immune tolerance in pig-to-primate, e.g., pig-to-human, heart transplantation.
Moreover, prior to the effective filing date of the instantly claimed invention, artisans in the field of xenotransplantation sought to solve the problem of adverse immune responses of pig-to-human cell transplantation. PD-L1 inhibits autoreactive T cells by binding to PD-1 on the T cells, and modifying porcine cells to recombinantly express human PD-1L (hPD-L1) has been shown to mitigate attacks from the human immune system. See, e.g., Abstract, Introduction on pg. 2, and Discussion on pg. 9-13, of Buermann.
Accordingly, one of ordinary skill in the art would have recognized that recombinant human PD-L1 expression would have been beneficial for xenotransplantation, i.e., transplantation of cells, tissues or organs into a human subject from a nonhuman animal source, e.g., a pig.
Xiaofeng does not teach that the vector is a CpG-depleted vector, as instantly claimed in claim 16.
Faust is relevant prior art for teaching that unmethylated CpG motifs found in therapeutic expression cassettes packaged in AAV capsids may be recognized by TLR9 and induce an immune response. Faust found that this immune response may be evaded by using CpG-depleted vectors, establishing prolonged transgene expression. See, e.g., page 2994.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the composition of Xiaofeng by using a CpG-depleted vector for transgene expression, as taught by Faust, with a reasonable expectation of success because CpG-depletion evades TLR9-directed immune responses and establishes prolonged transgene expression.
Accordingly, the prior art is found to teach or fairly suggest a composition comprising a CpG-depleted AAV vector comprising a nucleic acid that encodes human PD-L1 and an organ preservation solution comprising one or more preservatives, as instantly claimed.
The preamble of claim 16 further recites that the composition is “for preparing human donor tissue for transplantation.”
As instructed by MPEP 2111.02, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000) (holding that the preamble phrase "which provides improved playing and handling characteristics" in a claim drawn to a head for a lacrosse stick was not a claim limitation).
In this case, the preamble of claim 16 describes a purpose and/or intended use of the composition recited in the body of the claim. The preamble does not positively recite any distinct definition of any of the claimed invention’s limitations. In particular, describing the composition as being intended for “preparing human donor tissue for transplantation” does not necessarily further limit the CpG-depleted AAV vector comprising a nucleic acid encoding human PD-L1 nor the organ preservation solution comprising one or more preservatives. Thus, absent evidence to the contrary, the purpose and/or intended use recited by the preamble of claim 16 is not found to patentably distinguish the instantly claimed invention from the prior art.
For these reasons, claim 16 would have been prima facie obvious over the prior art.
Regarding dependent claim 20, the recitation that the human donor tissue is cardiac tissue is directed to the purpose and/or intended use recited by the preamble of claim 16, i.e., “[a] composition for preparing human donor tissue for transplantation.” Accordingly, dependent claim 20 is not found to patentably distinguish the instantly claimed invention from the prior art for the same reasons provided above for the preamble of claim 16.
Claims 17 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Xiaofeng et al. (2010) “AAV based gene delivery to myocardium in rodents and pigs” Xenotransplantation, 17(2), 111; Buermann et al. (15 Feb 2018) “Pigs expressing the human inhibitory ligand PD‐L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties” Xenotransplantation, 25(5), e12387, 15 pages; and Faust et al. (2013) “CpG-depleted adeno-associated virus vectors evade immune detection” The Journal of clinical investigation, 123(7), 2994-3001, as applied to claims 16 and 20 above; in view of Piacentino III et al. (2012) "X-linked inhibitor of apoptosis protein-mediated attenuation of apoptosis, using a novel cardiac-enhanced adeno-associated viral vector" Human gene therapy, 23(6), 635-646.
This rejection is newly applied, necessitated by amendment.
Xiaofeng and Faust do not teach that the vector is a SASTG AAV vector, as instantly claimed in dependent claim 17.
Prior to the effective filing date of the instantly claimed invention, Piacentino teaches the design of a novel AAV vector, termed SASTG, that achieves highly efficient transduction in myocardial tissues (Abstract), finding that SASTG AAV more effectively transduced cardiac muscle and cardiomyocytes relative to other AAV serotypes (Figures 3-4).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the composition of Xiaofeng by using an SASTG AAV vector for gene transfer, as taught by Piacentino, with a reasonable expectation of success because the SASTG AAV vector achieves highly efficient transduction in myocardial tissues.
Regarding dependent claim 21, Piacentino discloses that the SASTG vector is a novel AAV type 3b (AAV3b) vector, as instantly claimed. See, e.g., pg. 636, col. 1-2, bridging paragraph; pg. 638, right column; pg. 639, right column.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached on (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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