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 of Group II, claims 32-33 in the reply filed on 10-13-2025 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Claims 16-31 and 34-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group/Inventions, there being no allowable generic or linking claim.
Therefore claims 32-33 are examined on the merits below.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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.
the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) a tissue organ or cells (claim 32) particularly bone marrow stem cells (claim 33) from which CMV infected cells have been removed. Therefore the product claimed is simply for example, bone marrow stem cells which do not comprises CMV infected cells. Therefore the product is identical to bone marrow stem cells that may be found in an individual subject which has never been exposed to the CMV virus, or alternatively a subject which has been exposed to the virus, but has cleared the virus and/or latent infection was never stably established. The product claimed therefore does not have markedly different characteristics compared to a naturally occurring tissue, organ or cells which were never infected with CMV virus or from which CMV virus was naturally cleared by the subject’s native immune system.
This judicial exception is not integrated into a practical application because the remainder of the instant claim 32 for instance is a product by process limitation wherein the CMV free product is produced through incubation of a tissue with an antibody directed to the extracellular region of CMV US28 and is nothing more than an attempt to generally link the product of nature (CMV “free” ) to a particular technological environment.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
If Applicant would further argue that the inventive concept of removal of CMV infected cells may amount to significantly more than the judicial exception. However the disclosure of Weekes (WO2015073788A2) for instance relates to methods of treating HCMV infection whereby an agent, for example a therapeutic antibody, which specifically binds to an HCMV protein that is expressed on the plasma membrane of a HCMV infected cells (p10-p11)(Table 1, Table 2, “US28”). Therefore removal of HCMV infected cells, for example “treatment” of HCMV infected individuals, specifically through the use of therapeutic antibody directed to infected cells plasma membrane proteins such as US28 was previously known in the art and routine and conventional. Weekes specifically considers “nanobody” (VHH, single variable heavy-chain antibody) (p2, 14-24). Treated individuals would naturally comprise in their marrow stem cells from which CMV infected cells were removed. Alternatively the cells may be considered to be “CMV free” as instantly claimed product of nature.
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.
Claims 32, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12037382 in view of Weekes.
The reference claims describe single heavy chain variable domain antibody directed to extracellular region of the CMV US28 protein. The disclosure of Weekes provides methods of treating individuals with CMV infection with antibody directed to the plasma membrane cell surface proteins for example US28 as indicated above. It would thus be obvious to treat a subject who is infected with the US28 antibody of the reference claims, subjects thereby treated would inherently be “CMV free” and thereby comprise in their bone marrow for example stem cells from which cells that were infected with CMV have been removed.
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)(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) 32, 33 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Smit (WO2019151865A1; of record IDS).
The applied reference has a common Inventors/Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
The inventors of Smit created a VHH directed to the extracellular domain of the CMV US28 protein (p25 Example 1). The inventors of Smit further provided in-vivo treatment of mice (p32 4-22) that had been inoculated with glioblastoma tumor cells which comprised on their surface the CMV US28 protein. Thus the inventors of Smit incubated the tissue (introduced GBM cells) with a single chain heavy chain variable domain antibody against HCMV US28. Therefore the disclosure of Smit provides the same process utilizing an identical antibody, which would therefore inherently provide for the claimed function of reactivation of CMV in infected cells and subsequent cellular lysis, resulting in “CMV free” cellular composition. Additionally regarding the instant claim 33, the antibody was administered systemically and therefore it would be expected to eliminate/bind to any HCMV cells in the mouse bone marrow thus providing mouse bone marrow stem cells from which any HCMV infected cells were removed.
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.
Claim(s) 32, 33 are rejected under 35 U.S.C. 102(a1) as being anticipated by Trono et al (WO2015091506A1).
Claim 32 describes a tissue organ or cells “from which cells which were infected with CMV have been removed by incubating the cells with a single heavy chain variable domain antibody that binds to the extracellular region of human cytomegalovirus protein US28”.
Claim 32 is a product by process claim. [E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Regarding claim 32 the disclosure of Trono et al (WO 2015/091506 A1) relates to a method for purging ex vivo isolated organs or isolated cells from latent human cytomegalovirus (HCMV)(abstract)(p4 10-17).
In anticipation of the instant claimed “cells” of claim 32 and particularly “bone marrow stem cells” of claim 33 the disclosure of Trono provides composition particularly related to KAP1 proteins with a phosphorylated serine on position 824 and additional related compositions which are capable of purging latently HCMV infected cells (p5, especially 1-15). The cells which may be purged by the particular agents of the invention may be for instance HCMV positive bone marrow, which anticipates the instant claims 32 and 33 for instance. Additionally ex-vivo isolated organs and isolated cells are contemplated as targets which may be processed to provide the “CMV-free” organs and/or cell isolates of the instant claim 32, 33 (p4, 10-15). Interestingly therefore the provided CMV free isolates would qualify as “tissue, organ or cells from which cells that were infected with CMV have been removed” as in claim 32. .
Claim Rejections - 35 USC § 103
Claim(s) 32,33 are rejected under 35 U.S.C. 103 as being unpatentable over Weekes et al. Claim 32 describes a tissue organ or cells “from which cells which were infected with CMV have been removed by incubating the cells with a single heavy chain variable domain antibody that binds to the extracellular region of human cytomegalovirus protein US28”.
Regarding the instant claims the disclosure of Weekes provides methods of treating HCMV infection in a subject particularly through the use of agents which bind to target proteins expressed on the plasma membrane of HCMV infected cells (p2-3). Particularly antibody are disclosed including “nanobody” as single heavy chain variable domain antibody. Thus subjects of the invention of Weekes would be expected to be treated with potentially a US28 directed “nanobody” as a target disclosed in tables I and tables II of the specification. Utilization of the antibody in-vivo would thus provide for tissues which previously were infected with the CMV virus that were removed as an inherent property of the treatment performed leaving tissues including bone marrow which is substantially “CMV free”. Considering the disclosure of Weekes it would be obvious to provide an antibody directed to the US28 antigen for example and treat a subject with said antibody thereby finally providing tissues, such as bone marrow which are substantially free of CMV infected cells.
Claim(s) 32, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Heukers et al (Oncogene (2018) 37:4110–4121) and Krishna et al (NATURE COMMUNICATIONS | 8:14321 | DOI: 10.1038) both of record IDS-02-01-2022. The disclosure of Heukers describes nanobodies which bind to the N-terminal extracellular domain of HCMV US28 in HCMV infected cells (Heukers, figures 4-5). The disclosure of Krishna describes the beneficial effects of the reduction of latent HCMV load in hematopoietic stem cell transplantation would have far reaching clinical benefits (Krishna, abstract). The disclosure of Krishna describes a CX3CL1-toxin fusion protein designated F49A-FTP which upon binding of the CMVUS28 GPCR is capable of reducing CMV reactivation in vitro through destruction of infected cells. In particular embodiment the instant claim method/products utilize toxin tagged VHH antibody which binds to the CMVUS28 molecule. It would therefore be obvious considering the disclosure of Krishna and Heukers to arrive at the instantly claimed tissue, cell or organs through utilization of the instantly claimed VHH antibody as disclosed by Heukers for the purposes of in one instance treating a population of HSC derived from a subject to eliminate CMV infected cells resulting in a population of cells which is free of CMV and thereby reducing the chances of deleterious CMV reactivation in the situation of transplant of subjects who may be already immunocompromised.
Conclusion
Summary: No claims are allowed
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/BRIAN HARTNETT/Examiner, Art Unit 1644
/JANET L ANDRES/Supervisory Patent Examiner, Art Unit 1671