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 and remarks, filed 12/2/25, are acknowledged.
Claims 1-2, 5 and 13-14 have been amended.
Claims 1-2, 5, 8, 13-14 are pending and are under examination..
In view of Applicant’s claim amendments, the previous grounds of rejection are withdrawn. The following are new grounds of rejection necessitated by Applicant’s claim amendments. Applicant’s arguments relevant to the new grounds of rejection will be addressed below.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
Applicant states that this application is a divisional application of the prior-filed application. A continuation or divisional application cannot include new matter. Applicant is required to delete the benefit claim or change the relationship (continuation or divisional application) to continuation-in-part because this application contains the following matter not disclosed in the prior-filed application:
The prior filed application 15/767,577, upon which priority is claimed as a DIV, claimed a method of enriching organ or tissue derived microvesicles comprising obtaining a biological sample from a subject and contacting the biological sample with an antibody specific for a protein to isolate, purify, or identify the donor organ or tissue derived microvesicles from the biological sample. The ‘577 claimed that the protein is a MHC protein specific for a particular organ or tissue derived microvesicle. The ‘577 application also discloses that microvesicles can be isolated by several capture and enrichment platforms known in the art, including anion exchange and/or gel permeation chromatography, density centrifugation, or MACs sorting (see pages 27-28, in particular). The ‘577 application discloses that in certain embodiments, microvesicles are isolated from a biological sample using MHC proteins that reside on the surface of microvesicles, and that in certain embodiment microvesicles can be enriched are those originating from a donor using a donor HLA profile (see pages 28-29, in particular). In other words, the disclosure is limited to the use of antibodies that bind to MHC or HLA expressed on the surface of the donor specific microvesicles, or antibodies that bind to an HLA type originating from the donor.
However, the present claims encompass isolating microvesicles of a transplant from a donor using any “antibody binding to HLA or MHC”. For example, the claims would encompass any HLA type, not just that of donor of the transplant or those HLA molecules that are present on the surface of the microvesicles form the transplant donor, as disclosed in the prior filed application.
Furthermore, the present claims are directed to a method wherein microvesicles are isolated by obtaining a fraction of a plasma by high exclusion limit chromatography, and the fraction is further contacted with donor specific anti-HLA antibody to isolate donor specific microvesicles. None of the above embodiments disclosed or claimed in the priority document are directed to such as combination of method steps employing both high size exclusion limit chromatography to obtain a fraction, and contacting the fraction with an anti-HLA antibody.
The ’577 application does discloses that in certain embodiments high exclusion limit agarose based gel chromatography can be utilized to isolate total microvesicle fractions, and that the fractions comprising microvesicles can be used for affinity separation of organ or tissue specific microvesicle subpopulations such as using antibodies specific for a microvesicle surface protein, e.g. the donors MHC profile (See pages 29-30, in particular).
However, the present claims are not limited to high exclusion limit agarose based gel chromatography and nor using the donors MHC prolife, as disclosed in the prior filed ‘577 application, but broadly encompass any type of “high exclusion limit chromatography” with any antibody binding to any HLA or MHC, which is broader in scope than what is disclosed in the parent application. Furthermore, the claims are not limited to isolation of a fraction of total microvesicles as disclosed in the ‘577 application, but broadly encompass obtaining any fraction of the biological sample by size exclusion chromatography.
Regarding the amendments to claim 1, the claims, as amended, now recite specific transplants that are pancreatic islet, beta cell islet, or a pancreatic tissue transplants, and isolating microvesicles by a specific combination of steps using high exclusion limit chromatography and an antibody binding to HLA or MHC, and contacting the microvesicles with an antibody that binds a biomarker “selected from insulin, FXYD2, Hsc-70, antgiopoietin-1, hemopexin, complement C3, ZnT8, GAD65 or a combination thereof”. This combination of elements is not supported in the disclosure of the ‘577 application. For example, on pages 24-26, the ‘577 discloses isolating proteins from a pool of one or more organ or tissue derived microvesicles (from the donor and/or subject) which can be Hsc-70, angiopoiet-1, hemopexin, and/or complement C3. However, the present claims are not limited to protein isolation of biomarkers. This paragraph does not mention combining, for example, Hsc-70 with insulin, as encompassed by the present claims.
On pages 24-26, the ‘577 application discloses a different embodiment wherein islet cell derived exosomes express FXYD2, insulin, GAD65 and/or ZnT8, which allows for islet cell specific characterization of exosomes. However, the present claims encompass not only islet transplants, but also “pancreatic tissue”, for example. The ‘577 application does not specifically disclose characterizing exosomes from pancreatic tissue with the specific method steps of the instant claims. Furthermore, the present claims encompass combinations of said islet cell derived exosome markers, such as insulin, in combination with Hsc-70, which is also not supported by the ‘577 application.
It is also noted that the present claims broadly encompass contacting with said antibody binding a biomarker selected from insulin, FXYD2, Hsc-70, antgiopoietin-1, hemopexin, complement C3, ZnT8, GAD65 or a combination thereof. This would encompass contacting to detect the biomarker, to isolate the microvesicles, or modulate activity of the biomarkers, for example. This is broader in scope than what is disclosed in the ‘577 application. The ‘577 application discloses, for example, that certain biomarkers are detected by contacting with an antibody, or wherein, for example, wherein antibodies to FXYD2 can be used to enrich microvesicles. However, the present claims encompass, for example, contacting with an insulin antibody to enrich microvesicles, which is not contemplated in the ‘577 application.
The present claims encompass a specific combination of elements, and the priority document does not adequality describe the specific combination of elements of the instant claims arranged in the manner of the instant claims. To be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, the claim limitations must be expressly, implicitly, or inherently supported in the originally filed disclosure. The prior filed application does not provide ipsis verbis disclosure of the claimed method and also does not provide sufficient blaze marks to show express, implicit or inherent support under 35 U.S.C.112(a) for the presently claimed method. See MPEP 2163 II. 3(b).
Consequently, the claims have been accorded the priority of the filing date of the instant application, i.e. 4/3/24.
It is noted that Applicant does not cite any support in the prior filed application for the presently claimed method.
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.
Claim 1-2, 5, 8, 13-14 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.
Claim 1 is directed to a method for enriching microvesicles “of a transplant from a donor” comprising obtaining a plasma sample “from a recipient of the transplant” and isolating the microvesicles “from the transplant”. The scope of the claimed method is unclear and indefinite. For example, while a plasma sample is obtained from a recipient of the transplant, the claims do not require that the microvesicles are isolated from said plasma sample. The preamble, and step b), would appear to encompass enriching microvesicles from a transplant donor, or from a transplant isolated from a donor, for example. It is unclear how the plasma sample is used in the claimed method. Are the claims intending to require that the isolation step (b) is from the plasma sample of the recipient of the transplant from the donor?
Claim 5 recites the limitation “the protein” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation “the subject” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 13 and 14 recite the limitation of “the antibody”, however, in claim 1 there are two antibodies recited, an antibody binding to HLA or MHC, and an antibody binding a biomarker. It is unclear which antibody is being referred to. For example, would claim 14 encompass a method wherein the insulin antibody from claim 1 is conjugated with magnetic beads?
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 5, 8, 13-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
A method for enriching microvesicles of a transplant from a donor comprising obtaining a fraction with “high exclusion limit chromatography” and contacting the fraction with “an antibody binding to HLA or MHC”. (Claim 1, and dependent claims).
A review of the specification fails to reveal support for the new limitations.
At page 29, the specification discloses “high exclusion limit agarose-based gel chromatography”, however, this has a narrower scope than the instant claims which are not limited to high exclusion limit “agarose based gel” chromatography, but encompass any high exclusion limit chromatography. Furthermore, the original claims required contacting with a donor specific anti-HLA antibody, but now encompass contacting with any “antibody binding to HLA or MHC”. The instant specification discloses that in certain embodiments, microvesicles are isolated from a biological sample using MHC proteins that reside on the surface of microvesicles, and that in certain embodiments microvesicles can be enriched are those originating from a donor using a donor HLA profile (see pages 28-29, in particular). In other words, the disclosure is limited to the use of antibodies that bind to MHC or HLA expressed on the surface of the donor specific microvesicles, or antibodies that bind to an HLA type originating from the donor.
However, the present claims encompass isolating microvesicles of a transplant from a donor using any “antibody binding to HLA or MHC”. For example, the claims would encompass any HLA type, not just that of donor of the transplant or those HLA molecules that are present on the surface of the microvesicles from the transplant donor, as disclosed in the specification.
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) 1-2, 5, 8, 13-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vallabhajosyla, 2017.
Vallabhajosyla teaches a method of enriching donor derived microvesicles (exosomes) comprising obtaining a plasma sample from a subject who has received a pancreatic islet cell transplant from a donor, isolating donor specific microvesicles from the sample comprising obtaining a fraction of the biological sample by size exclusion limit gel chromatography, contacting the fraction with a donor specific anti-HLA-A antibody conjugated to magnetic beads, and isolating anti-HLA-A antibody bound donor specific microvesicles in the fraction (see pages 1388-1389). Vallabhajosyla further teaches detecting biomarkers on the microvesicles by contacting the microvesicles with antibodies to biomarkers such as an antibody to FXYD2 (see Fig. 7). Vallabhajosyla teach human subjects (see pages 1388-1389).
Applicant argues that the claims have been amended to incorporate claim 6, which was not rejected as anticipated by Vallabhajosyla.
Claim 6 required a biomarker selected from (Hsc-70), angiopoietin-1, hemopexin, complement C3, ZnT8, GAD65, or a combination thereof, which was not explicitly taught in Vallabhajosyla. However, claim 1, as amended, is not limited to the biomarkers from previous claim 6, but also encompasses contacting with an antibody binding a biomarker selected from “FXYD2”, which is taught by Vallabhajosyla for the reason set forth above.
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 1-2, 5, 8, 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 19/028,022, in view of Vallabhajosyla, 2017.
The ‘022 application claims a method comprising obtaining a biological sample from a human subject that has received a transplant, wherein the sample comprises subject derived and donor derived microvesicles, producing a fraction of the sample by isolating microvesicles, and purifying donor derived microvesicles by using a donor specific anti-MHC antibody. The ‘022 application claims that the transplant is pancreatic islet. The ‘022 application claims further comprising measuring expression of other markers in the microvesicles (i.e. biomarkers). The ‘022 application claims that the microvesicles are isolated by high exclusion limit agarose based gel chromatography.
Regarding the other biomarkers of the instant claims, it would be obvious to perform the microvesicle isolation method using a plasma samples and other types transplant specific biomarkers, such as FXYD2 for validation purposes, as taught by Vallabhajosyla for the same reasons set forth above. Furthermore, it would be obvious to use the HLA-A antibody conjugated to magnetic beads of Vallabhajosyla since the reference teaches it is suitable for isolation of donor specific microvesicles.
This is a provisional nonstatutory double patenting rejection.
Applicant’s statement that the rejection be held in abeyance until the time of allowance is acknowledged.
No claim is allowed.
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 extension fee 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 date of this final action.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644