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 .
The claims dated 5/22/2026 are under consideration.
Election/Restrictions
The election of species requirement is withdrawn upon search and consideration of the elected species.
Priority
The present application is a 371 national stage entry of PCT/US2022/037938 (filed 7/21/2022), which claims benefit of US provisional application 63/224,380 (filed 7/21/2021).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because multiple nucleic acid sequences as disclosed in the specification (e.g., p. 359, 360, 361, etc.)..
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specification
The use of terms, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 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 1, the claim recites “the determined quantity classifies a subject as having or being susceptible to prostate cancer when the determined quantity is elevated relative to a reference threshold”. It is unclear if the claim further requires an active method step of “classifying” a subject as having or being susceptible to prostate cancer or “determining” an elevated quantity relative to a reference threshold. Further, it is unclear if the claim is limited to biomarkers associated with prostate cancer and the sample being one obtained from a subject, as the active method steps themselves to do not specify those details.
Claims 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 depend from claim 1 and are rejected for the same reason.
Regarding claim 7, based on the use of the passive voice, it is unclear if the claim requires an active method step of “determining the reference threshold by levels of target biomarker signature-expressing extracellular vesicles observed in comparable samples from a population of non-cancer subjects”.
Claim 8 depends from claim 7 and is rejected for the same reason.
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, 2, 3, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Routenberg (WO 2020/086751 A1).
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Regarding claim 1, Routenberg teaches a method as depicted in Figures 1, 2, 7, 19, 32, 33, 34, 35, 36 and 48. Figure 48C is reproduced below with Examiner’s annotations for mapping of claim elements:
Routenberg teaches capturing an “extracellular vesicle” or EV from a sample with the “capture agent” Antibody 4: Capture Antibody that binds a “first biomarker” on the EV.
Routenberg teaches binding the Antibody 1 with Primer Oligo as a “first probe comprising a first oligonucleotide” to a “second target biomarker” of the “captured” EV.
Routenberg teaches binding the Antibody 2 with Splint Oligo as a “second probe comprising a second oligonucleotide” to a “third target biomarker” of the “captured” EV.
Routenberg teaches determining the quantity of the EV that are captured and bound by the antibodies through a nucleic acid-based assay involving a Detection Region of a Circular DNA template.
The claim concludes with a “wherein” clause stating “the determined quantity classifies a subject as having or being susceptible to prostate cancer when the determined quantity is elevated relative to a reference threshold”. The clause does not set forth any additional active method steps and does not further element any of the positively recited active method steps of claim 1. The clause is broadly interpreted as setting forth an intended use of the claimed method and does not further limit the scope of the active method steps.
Regarding claim 2, as depicted above, Routenberg teaches the second and third biomarkers are two different polypeptides on the surface of the EV. See also, para. 269 and 589 referring to 4-marker combination.
Regarding claims 3 and 5, Routenberg teaches detecting multiple types of EVs, e.g., EV Type A or EV Type B, using different combinations of antibodies targeting different surface biomarkers, which produce multiple different signatures. See, e.g., Fig. 36.
Regarding claim 6, Routenberg teaches biomarkers that are surface and intravesicular biomarkers (para. 268 and 526-528).
Regarding claims 7 and 8, the claims do not further limit the positively recited, active method steps of claim 1.
Routenberg anticipates claims 7 and 8 for the same reasons as claim 1.
Regarding claim 9, Routenberg teaches the sample is subjected to size exclusion chromatography to purify EVs (para. 66, 150, 208 and 223).
Regarding claims 12 and 13, Routenberg teaches a solid substrate in the form of magnetic beads (para. 170, 269, 270).
Regarding claim 14, as noted above, Routenberg teaches a “target-capture moiety” or “capture agent” in the form of an antibody.
Regarding claim 15, as noted above, Routenberg teaches performing a “detection assay” that is a nucleic acid-based assay involving a Detection Region of a Circular DNA template.
Regarding claim 16, Routenberg teaches a “capture assay” prior to the “detection assay” (see, e.g., para. 427-433).
Regarding claim 18, Routenberg teaches the “second target biomarker” is intravesicular and fixation and/or permeabilization of the EVs prior to detection (para. 39, 268, 526-528).
Regarding claims 19 and 20, as depicted above, the “detection assay” is a “proximity ligation assay”.
Regarding claim 115, Routenberg teaches PD-L1 (or “CD274”) (para. 129, 138), CD38 (para. 116-117) or EPCAM (para. 111), as one of the biomarkers on the surface.
Regarding claim 116, Routenberg teaches CD24 may be the biomarker (para. 112).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4, 115 and 116 is/are rejected under 35 U.S.C. 103 as being unpatentable over Routenberg (WO 2020/086751 A1) in view of Overbye (Oncotarget. 2015. 6(30):30357-30376 and Supplementary Material).
Regarding claims 1 and 4, Routenberg teaches a method as depicted in Figures 1, 2, 7, 19, 32, 33, 34, 35, 36 and 48. Figure 48C is reproduced above with Examiner’s annotations for mapping of claim elements.
Routenberg teaches capturing an “extracellular vesicle” or EV from a sample with the “capture agent” Antibody 4: Capture Antibody that binds a “first biomarker” on the EV.
Routenberg teaches binding the Antibody 1 with Primer Oligo as a “first probe comprising a first oligonucleotide” to a “second target biomarker” of the “captured” EV.
Routenberg teaches binding the Antibody 2 with Splint Oligo as a “second probe comprising a second oligonucleotide” to a “third target biomarker” of the “captured” EV.
Routenberg teaches determining the quantity of the EV that are captured and bound by the antibodies through a nucleic acid-based assay involving a Detection Region of a Circular DNA template.
The claim concludes with a “wherein” clause stating “the determined quantity classifies a subject as having or being susceptible to prostate cancer when the determined quantity is elevated relative to a reference threshold”. The clause does not set forth any additional active method steps and does not further element any of the positively recited active method steps of claim 1. The clause is broadly interpreted as setting forth an intended use of the claimed method and does not further limit the scope of the active method steps.
Routenberg does not specifically teach the second and third target biomarkers required by claim 4 and encompassed by independent claim 1 in an alternative embodiment.
However, Overbye teaches prostate cancer biomarkers found in urinary exosomes.
Regarding claims 1 and 4, Overbye teaches CLDN3/Claudin-3 and RAB3B/Ras-related protein Rab-3B (Table 1) as biomarkers
It would have been prima facie obvious at the time of invention to have modified the method of Routenberg by detecting the prostate cancer biomarkers of Overbye. One would have been motivated to make such a modification as it renders the method of Routenberg a prostate cancer specific assay. The modification has a reasonable expectation of success as it simply involves replacing the detection reagents of Routenberg with reagents that detect the prostate cancer biomarkers of Overbye.
Regarding claim 115, Overbye teaches prostate cancer biomarkers include RAB3B or RAB3D (Table 1).
Regarding claim 116, Overbye teaches prostate cancer biomarkers include Plastin-2/LCP1 (Table 1).
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 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/580,422 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘422 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-9, 12-16, 19-20 and 115 of copending Application No. 18/580,444 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘444 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/580,427 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘427 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/580,440 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘440 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/580,445 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘445 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/580,412 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘412 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 120-122, 125-127, 130-131, 134-143 of copending Application No. 17/435,697 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘697 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 120, 128, 131-133, 135-138 and 233 of copending Application No. 17/204,773 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘773 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 18, 19, 20, 115 and 116 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,085,089.
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are generic assay with dependent claims involving specific biomarkers, which encompass and/or are rendered obvious the methods of the ‘089 patent.
Conclusion
No claims allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
Prosecution Insights