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 .
Priority
The instant application claims the benefit of provisional U.S. Patent Application No. 63/190,079, filed on 05/18/2021.
The priority date of claim 1 and its dependents is determined to be 05/18/2021, the filing date of provisional U.S. Patent Application No. 63/190,079.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/30/2025 has been entered.
Status of Claims
New claim 21 is acknowledged.
Claims 1-9 and 12-21 are pending and under examination.
Response to Remarks filed 01/29/2026
The amendments and arguments presented in the papers filed 01/29/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/31/2025 and the advisory action dated 01/27/2026 listed below have been reconsidered as indicated.
a) Applicant’s arguments, with respect to the rejection of claims 1-9 and 12-18 as being unpatentable over Gaige (US 2019/0276820) in view of Meltzer (WO2020/069298) and with respect the rejection of claims 19 and 20 over Gaige and Meltzer and further in view of Spetzler (WO2014/100434) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection as presented below.
b) Applicant’s arguments, with respect to the double patenting rejections have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection as presented below.
New and modified grounds of rejection are detailed below.
Claim Rejections - 35 USC § 112(b)
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 1-9 and 12-21 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.
The preamble of claim 1 recites the limitation “a method for single cell analysis”. It is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble does not clearly set forth the metes and bounds of the claim and is therefore indefinite. The method steps of the claim only require active steps directed towards extracellular vesicles. Thus it is unclear if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of single cell analysis as set forth by the preamble of the claim
Claim 1 recites the limitation “analyzing – to determine one or more characteristics of the cell”. It is unclear what cell is referred to as the claims are directed to extracellular vesicles. It is unclear if what is intended is the extracellular vesicle, or the cell which the extracellular vesicle was released from.
Claims 2-9 and 12-21 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 4 recites the limitation "the released nucleic acid" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. Claim 1, which claim 4 depends on recites “released RNA”. Nucleic acid would further comprise DNA.
Claim 6 recites the limitation “identifying from the sequence reads -- nucleic acids --”. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites the limitation "EVs in the aqueous mixture”. There is insufficient antecedent basis for this limitation in the claim. There is no aqueous mixture recited in the claims which claim 14 depends from.
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.
Claims 1-9, 12-17, and 20- 21 are rejected under 35 U.S.C. 103 as being unpatentable over Ko et al. (WO 2021067162, published 04/08/2021) in view of Meltzer et al. (WO/2020/069298, on IDS dated 11/02/2022).
Regarding claim 1, Ko teaches methods of analyzing protein compositions from individual extracellular vesicles (EVs) from biological samples comprising: isolating EVs from a biological sample; labeling the EVs with antibody-DNA conjugates (target-specific antibodies linked to index oligonucleotides); obtaining barcoded beads (template particles); encapsulating the labeled EVs (i.e. bound by the antibody) and barcoded beads in droplets (partitions) (p. 3, lines 7-12). Ko teaches any antibody that targets a specific surface EV protein of interest can be used (target-specific antibodies that bind to EV surface proteins) (p. 12, line 26). Ko teaches droplets (partitions) are generated by adding oil to form water in oil partitions (p. 9, lines 21-22). Ko further teaches the antibody comprises a barcode region (index oligonucleotide) (p. 7, lines 10-12 and Fig. 1B). The antibody-DNA barcode region can be used to tell which sequences came from which EVs once sequencing is done, which reads on analyzing the index oligonucleotides to determine one or more characteristics of the cell (p. 13, lines 9-11 and Fig. 2). Ko also teaches the barcoded beads (template particles) comprise hybridization regions that include complementary sequence to the sequence of the DNA on the antibody-DNA conjugate (i.e. capturing antibodies on the template particle) (p. 3, lines 24-27 and p. 13, lines 29-30).
Ko does not teach (i) capture oligonucleotides on the beads that capture released RNA, (ii) shearing the mixture to form a plurality of water-in-oil partitions or elements requiring RNA, or (iii) lysing the extracellular vesicles to release RNA within each partition; capturing released RNA on the template particle within each partition; reverse transcribing the released RNA captured by the capture oligonucleotide to produce cDNA and analyzing the cDNA to determine one or more characteristics of the cell.
Meltzer teaches methods of target capture and barcoding in monodisperse droplets, including barcoding of specific nucleic acids, including RNA, contained in the captured targets (Abstract). The methods comprise combining capture template particles with a first fluid comprising target particles (para 6) such as extracellular vesicles (para 7). Meltzer teaches template particles that can capture antibodies and polynucleotides (para 5).
Regarding (i), Meltzer teaches capture template particles comprise oligonucleotides that are capture element genetic identifiers (capture oligonucleotides) (paras 4-5) that can capture released nucleic acids including released mRNA (paras 7, 18, 70). Meltzer also teaches template particles with multiple capture elements, including capture moieties for antibodies (Fig. 8).
Regarding (ii), Meltzer teaches shearing or partitioning such that the capture template particles and associated exosomes are encapsulated in a plurality of monodisperse droplets in the partitioning oil (i.e. water-in-oil partitions) such that each capture template particle and associated exosome are encapsulated in a single monodisperse droplet (para 18).
Regarding (iii) Ko states that EVs contain small amounts of nucleic acids reflective of those found in parental cell (p. 16, lines 10-13) but does not teach a method for identifying the nucleic acids in an EV.
Meltzer teaches lysing the exosomes to release RNA within the partition (para 18) and capturing released mRNA with the Poly-T sequences (“Poly-T capture”) of the capture template particle’s capture element genetic identifier (para 18), thus capturing released RNA on the template particle within each partition. Meltzer further teaches
performing reverse transcription to generate cDNA templates of the associated mRNAs (para 18) and use target-specific capture element genetic identifiers comprise template-type elements which identify the target particle from which the nucleic acids were derived (para 62).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer to arrive at the instantly claimed invention. The combination would have entailed using the template particle with capture oligonucleotides of Meltzer in the method of Ko and generating the water-in-oil partitions by the method of Meltzer. One would have been motivated to use the shearing method of Meltzer by the ease of use (Meltzer, Fig. 9) compared to the droplet generating method of Ko which required a microfluidic device (Ko, Fig. 1C). One would have been motivated to use the capturing template particles of Meltzer in the method of Ko in order to perform multiplex analysis and characterize proteins and nucleic acids from a single (partitioned) extracellular vesicle. Ko recognized the presence of both proteins and nucleic acids in EVs that contained information about the parental cell. Droplet/partition capture and sequencing was well-known at the time to enable analysis of small amounts of proteins and nucleic acids. The template particles of Meltzer would have allowed both analytes to be analyzed simultaneously for a single EV. Further, Meltzer explicitly teaches the capturing of antibodies on a template particle by a capture moiety (paras 15 and 20 for example). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 2, Ko teaches a barcode (index oligonucleotide) that is specific to an antibody (Fig. 1B) and can be used to distinguish different antibodies (p. 13, lines 1-2), which reads on a barcode sequence that identifies a protein to which the antibody binds by knowing the protein which a specific antibody binds to.
Regarding claim 3, Ko teaches barcoded beads comprising a UMI region (p. 3, lines 24-25), i.e. a barcode unique to each template particle, and therefore partition-specific.
Regarding claim 4, Ko teaches preparing a sequencing library following reverse transcription and PCR (p. 9, lines 10-12 and Fig. 1A). Ko teaches generating cDNA from the DNA conjugate of the Antibody-DNA conjugate (comprising copies of the index oligonucleotide) (p. 3, lines 1-5 and Fig. 2). Ko teaches the library products contain the UMI (partition barcode) (p. 25 line 31 to p. 26, line 1 and Fig. 2).
Ko does not teach a sequencing library containing copies of the released nucleic acid.
Meltzer teaches performing reverse transcription to generate cDNA templates of the associated mRNAs and making sequence libraries from the products (para 8).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer to arrive at the instantly claimed invention. The modification would have entailed making sequencing libraries from all elements captured by the template particle of Meltzer. The modification would have entails preparing a sequencing library from capture oligonucleotides for released RNA as well as the captured DNA conjugates of Ko on the capture template particle of Meltzer. One would have been motivated by the ability to have a single sequencing library with both protein and mRNA information associated with a single EV. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 5, both Ko (p. 16, lines 3-5) and Meltzer (para 33-34 )teach sequencing the library.
Regarding claim 6, Ko teaches identifying EV proteins from sequence reads (p. 3, lines 17-18 and ). Ko also teaches barcoded beads (template particles) comprising a UMI region (p. 3, lines 24-25), i.e. a barcode unique to each template particle and thus each EV.
Ko does not teach identifying nucleic acids present in the EVs from the sequence reads.
Meltzer teaches a template particle may comprise a target-specific capture element genetic identifier that captures mRNA and a template ID element (referred to as “Template specific barcode”) (para 18). Reverse transcription generates cDNA templates of the mRNA along with the template specific barcode (para 18). PCR products can then be used to prepare a sequencing library (para 8) comprising cDNA from the mRNA and a template specific barcode, which reads on identifying nucleic acids present in the EVs.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer to arrive at the instantly claimed invention. The modification would have entailed incorporating a template-specific barcode into the sequencing library of capture mRNA on the template particle as in Meltzer and/or the UMI barcode of Ko into sequencing library products from the capture antibody-DNA conjugates. One would have been motivated by the ability of partitioning and template particle capture to associate both proteins and nucleic acids with an EV and better characterize EVs, a goal of both Ko and Meltzer. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 7, Ko teaches sequencing libraries comprise a UMI (partition barcode) (p. 25 line 31 to p. 26, line 1 and Fig. 2) and analyzing the sequences from
individual EVs to define their protein composition (p. 4, lines 7-8. See also sequencing library in Fic. 2C with all sequences in library containing the UMI partition barcode).
Ko does not teach capturing nucleic acids and thus does not explicitly teach using the partition barcodes in the sequence reads to identify nucleic acids of at least one individual EV.
Meltzer teaches using template ID elements or barcodes to identify amplification products from the same exosome (para 19).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer to arrive at the instantly claimed invention. The modification would have entailed using the captured antibody-DNA conjugate of Ko and the captured mRNA of Meltzer to generate products for a sequencing library containing both protein information (from the antibody) and nucleic acid information (from the captured mRNA) captured by an individual EV in a partition with a template particle. Both the antibody-DNA conjugate and mRNA could be captured on a single template particle comprising a unique template particle barcode as described in both Ko and Meltzer. One would have been motivated by the benefits of partitions to capture and label multiple elements from a single EV. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 8, Ko teaches the method can be used to identify EV subtypes (subclasses) (p. 3, lines 4-5) and enable discovery of EV subtypes (p. 8, lines 28-30). Ko further teaches the use of antibodies (which comprise index oligonucle3otides in the method of Ko) that target specific surface EV proteins (p. 12, line 26). Thus Ko teaches elements that satisfy the requirements of using the index oligonucleotide barcodes to identify an extracellular vesicle subclass of the individual EVs.
Regarding claim 9, Ko teaches the EVs can be microvesicles, exomeres, apoptotic bodies, oncosomes (p. 4, lines 27-28).
Regarding claims 12 and 13, Ko does not teach released RNA.
Meltzer teaches the released RNA can be mRNA (para 18, Fig. 4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer to arrive at the instantly claimed invention. The modification would have entailed using the capture elements of the template particle to capture mRNA as taught by Meltzer. One would have been motivated by the added ability to analyze extracellular vesicles in an additional dimension (mRNA expression) that was known to be accurate biomarkers. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 14, Ko teaches obtaining the biological sample from a subject (p. 4, lines 30-31).
Regarding claim 15, Ko teaches the method permits detection and identification of diseased EV subtypes (p. 3, lines 4-5) and can resolve the heterogeneity of EVs, i.e. subclass (p. 5, line 19). Ko further teaches analyzing protein composition from individual extracellular vesicles (EVs) from a biological sample; obtaining sequencing results; and analyzing the sequencing results (which contain surface protein identity) to determine if the subject has a disease (p.5, lines 1-3). Thus Ko teaches elements that satisfy the requirements of assessing pathology using extracellular vesicle subclass of one or more individual EVs in the sample.
Regarding claim 16, Ko teaches quantification of the number of EVs in a sample (p. 12, lines 14-15), which reads on quantifying amounts of individual EVs in the sample of a particular extracellular vesicle subclass.
Regarding claim 17, Ko teaches the method can be used to identify EV subtypes (subclasses) (p. 3, lines 4-5) and enable discovery of EV subtypes (p. 8, lines 28-30). Ko further teaches the use of antibodies (which comprise index oligonucle3otides in the method of Ko) that target specific surface EV proteins (p. 12, line 26). Thus Ko teaches elements that satisfy the requirements of analyzing the proteins identified in the EVs.
Regarding claim 20, Ko teaches the disease type can be cancer (p. 5, lines 7-8 and p. 17, line 27) and that EVs include oncosomes (p. 4, lines 27-28).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Ko to arrive at the instantly claimed invention. The modification would have entailed selecting cancer as the disease and oncosomes as the EVs. One would have been motivated by the fact that the EV class of oncosomes is associated with cancer. Kop explicitly states that a benefit of the method of single EV analysis allows insight into cancer and vesicles associated with cancer (p. 16 lines 28-31 to p. 17 lines 1-2 and p. 17, lines 29-31). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 21, Ko teaches breaking the droplets (partitions) (p. 15, line 15) and performing reverse transcription (p. 15, lines 28-31), satisfying the requirement of producing cDNA outside of the partitions. However, Ko does not teach reverse transcribing released RNA captured by the capture oligonucleotide.
Meltzer teaches reverse transcription to generate cDNA templates of the associated mRNAs and making sequence libraries from the products (paras 8 and 70).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer to arrive at the instantly claimed invention. The modification would have entailed using the method of Ko to break the droplets before performing reverse transcription, thereby producing cDNA outside the partitions, and performing RT on the captured mRNA of Meltzer. One would have been motivated to do so by the added benefit of making a library containing mRNA from an EV. One would also have been motivated by the benefits of performing reverse transcription in bulk rather than in single partitions that require individual portions of the appropriate levels of reagents. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claims 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ko et al. (WO 2021067162) in view of Meltzer et al. (WO/2020/069298, on IDS dated 11/02/2022) as applied to claims 1-9, 12-17, and 20-21 above, and further in view of Kawasaki et al. (US 20210396633A1 published 12/23/2021, filed 10/16/2019 and published as WO 2020080387 on 04/23/2020. Citations are to the US document).
Regarding claims 18 and 19, Ko teaches that any antibody that targets a specific surface EV protein of interest can be used (p. 12, line 26) but does not teach a panel of target-specific antibodies with each antibody one the panel binding to a different protein.
Kawasaki teaches a method for recovering extracellular vesicles from an extracellular vesicle-containing sample (abstract), the method comprising using antibodies as extracellular vesicle membrane-binding substances to bind to extracellular vesicle markers selected from a group of identified EV surface markers (i.e., a panel) including such as CD63, CD9, and Phosphatidylserine (para 56)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ko and Meltzer with Kawasaki to arrive at the instantly claimed invention. The modification would have entailed selecting antibodies targeting different surface proteins from the list of Kawasaki. One would have been motivated by the availability of a list of recognized extracellular vesicle membrane markers to choose from for the purpose of capturing EVs as in Ko and Meltzer. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
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.
(I). Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 12 and 16 of U.S. Patent No. 11866782 in view of Ko et al. (WO 2021067162). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims are species claims that anticipate the genus claims of instant application.
Regarding instant claim 1, claims 1, 7, 12 and 16 of the ‘782 patent satisfy the requirements of instant claim 1. Claim 1 of the ‘782 patent requires incubating a plurality of nucleic-acid-labelled, target-specific antibodies with a plurality of target cells to promote binding of the nucleic-acid-labelled, target-specific antibodies to target proteins expressed by the target cells; washing the incubated target cells to remove unbound nucleic-acid-labelled, target-specific antibodies; combining template particles and the washed target cells in a first fluid, wherein each template particle comprises first capture probes comprising capture sequences and second capture probes comprising template-switching oligos (TSOs); adding a second fluid to the first fluid; shearing the fluids to generate a plurality of monodisperse droplets simultaneously that contain a single one of the template particles and a single one of the target cells; the release of mRNA molecules, amplifying and sequencing nucleic acid labels from the nucleic-acid-labelled, target-specific antibodies to identify target proteins expressed by the target cells claim 1 of the ‘782 patent. Claim 7 of the ‘782 patent lysing each of the single target cells contained within the monodisperse droplets to release a plurality of distinct mRNA molecules; capturing the plurality of distinct mRNA molecules with the first capture probes; amplifying and sequencing the cDNA to quantify the plurality of distinct mRNA molecules. Claim 12 of the ‘782 patent requires the second fluid comprises an oil. Claim 16 of the ‘782 patent requires the template particles further comprise a plurality of capture probes comprising: a capture sequence that hybridizes to one or more of the plurality of distinct mRNA.
Thus claims 1, 7, 12 and 16 of the ‘782 patent teach elements of instant claim 1.
The claims of the ‘782 patent do not require the target-specific antibodies bind to an extracellular vesicle (EV) surface protein.
The teachings of Ko as they relate to these claims are given previously in this office action and are fully incorporated here.
(II). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 12,13,15-17, 97, 99, and 101 of copending Application No. 17/281,157 (reference application) in view of Ko et al. (WO 2021067162) and Meltzer et al. (WO/2020/069298).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are species claims that anticipate the genus claims of instant application.
Regarding instant claim 1, copending claim 12 requires combining a plurality of capture template particles with a first fluid to provide a first mixture, wherein the first fluid comprises a plurality of target particles, wherein each capture template particles comprises: a target-specific capture element; Anda target-specific capture element genetic identifier comprising a unique barcode sequence; association of the plurality of target particles to the plurality of capture template particles via the target-specific capture element, thereby forming a mixture comprising a portion of the plurality of target particles associated to the capture template particles; combining the second mixture with a second fluid; shearing such that a plurality of the capture template particles are encapsulated in a plurality of monodisperse droplets in the second fluid, thereby providing a plurality of monodisperse droplets comprising reaction buffer, one of the capture template particles, and one of the plurality of target particles associated to said capture template particles. Copending claim 13 requires that the second fluid comprises an oil. Copending claims 14-16 require that the first fluid comprises a biological sample (copending 14), the biological sample is a body fluid (copending 15), and the body fluid comprises target particles selected from the group consisting of -- extracellular vesicles (copending claim 16). Copending claim 97 requires target-specific capture element is attached to a capture moiety linked to the template particle. Copending claim 99 requires the target-specific capture element comprises a poly-T polynucleotide sequences, an aptamer, or an antibody. Copending claim 101 requires that the target-specific capture element genetic identifier comprises a template-type element comprising a barcode sequence corresponding to the target-specific capture element. Thus copending claims 12,13,15-17, 97, 99, and 101 teach elements of instant claim 1.
Copending claims do not require a target-specific antibody with an index oligonucleotide or released RNA captured by the template particle.
The teachings of Ko and Meltzer as they relate to these claims are given previously in this office action and are fully incorporated here.
This is a provisional nonstatutory double patenting rejection.
(III). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 6, 9-11 and 17 of copending Application No. 18/403,902 (reference application) in view of Ko et al. (WO 2021067162).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are species claims that anticipate the genus claims of instant application.
Regarding instant claim 1, copending claim 1 teaches a method for single cell analysis comprising: incubating a plurality of nucleic-acid-labelled, target-specific antibodies with a plurality of target cells to promote binding of the nucleic-acid-labelled, target-specific antibodies to target proteins expressed by the target cells; combining in a first fluid; adding a second fluid to the first fluid; shearing the fluids to generate a plurality of monodisperse droplets; and amplifying and sequencing nucleic acid labels from the nucleic-acid-labelled, target- specific antibodies to identify target proteins expressed by the target cells. Copending claim 5 teaches lysing the droplets to release mRNA and quantifying the mRNA, Copending claims 3,6,and 9-11 of the ‘902 application further teach nucleic acid labels with a unique molecular identifier sequence (copending claim 3), and a capture portion comprising a polyA sequence (copending claim 6);reverse transcribing the released RNA (copending claim 9) that the fluids for forming the droplets are aqueous (copending claim 10) and oil (copending claim 11). Copending claim 17 teaches template particles comprise a plurality of capture probes comprising :a universal primer sequence; at least one barcode; and a capture sequence that hybridizes to one or more of the plurality of distinct mRNA. Thus copending claims 1, 3, 5, 6, 9-11 and 17 teach elements of instant claim 1.
Copending claims do not teach target-specific antibodies bind to an extracellular vesicle (EV) surface protein.
The teachings of Ko as they relate to these claims are given previously in this office action and are fully incorporated here.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682