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 .
Office Action: Notice
Any objection or rejection of record in the previous Office Action, mailed 9/24/2025,
which is not addressed in this action has been withdrawn in light of Applicants' amendments
and/or arguments. This action is FINAL.
Claim Status
Claims 1-35 and 56-60 have been cancelled (7/28/2022). Claims 36-37, 39, 42-43, 45, 49-50, 52 have been amended (12/16/2025). No new matter was added. Thus, claims 36-55 are under examination.
Priority
Claims 36-55 receive a priority date of 11/15/2019, the effective filing date of Japanese Provisional Patent JP2019-207329. All priority documents have been received.
Objections Withdrawn
Specification:
The objections to the specification due to the use of a trademark or tradenames are withdrawn in view of Applicant’s amendments.
Drawings:
The objections to the drawings, specifically Figures 1 and 3, for missing sequences identifiers are withdrawn in view of Applicant’s amendments.
Claims:
The objection to claim 39 due to minor informalities is withdrawn in view of Applicant’s amendments.
New Objections
Claims 37-38 are objected to because of the following informality:
Claim 37 at line 1 recites “the method according to Claim 1” and claim 1 is a cancelled claim. Therefore, claim 37 is objected to under 37 CFR 1.75 (c) as being improperly dependent on a cancelled claim. Claim 37 must be amended to depend from a valid, existing claim or rewritten in independent form. Claim 38 is included in this objection due to its dependency on claim 37. Upon correction of the dependency, claims 37-38 will be examined on the merits.
Rejections Withdrawn
Claim Rejections - 35 USC § 112 (b)
The rejections to claims 36-55 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which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), are withdrawn due to Applicant’s amendments of claims 36, 37, 42, 43, 49 and 50.
Claim Rejections - 35 USC § 102
The rejection to claims 37-38 under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Domenyuk et al., (WO 2017/161357 A1, published 9/21/2017) is withdrawn due to improper claim dependency. Claim 38 is included in this withdraw due to its dependency on claim 37. Upon correction of the dependency, claims 37-38 will be examined on the merits.
New Rejections
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 36, 39-55 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 36 is rejected. Claim 36 recites the limitation "the quantity ratio" in step 5, line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the corresponding barcode RNA" in step 5, line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 36 recites the limitation "the information" in step 5, line 5. There is insufficient antecedent basis for this limitation in the claim.
Claims 39 and 40-41 are included in this rejection due to their dependency on claim 36.
Claim 42 is rejected. Claim 42 recites the limitation "the quantity ratio" in step 5, line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 42 recites the limitation "the corresponding barcode RNA" in step 5, line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 42 recites the limitation "the information" in step 5, line 5. There is insufficient antecedent basis for this limitation in the claim.
Claims 43-48 are included in this rejection due to their dependency on claim 42.
Claim 49 is rejected. Claim 49 recites the limitation "the quantity ratio" in step 5, line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 49 recites the limitation "the corresponding barcode RNA" in step 5, line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 49 recites the limitation "the information" in step 5, line 5. There is insufficient antecedent basis for this limitation in the claim.
Claims 50-55 are included in this rejection due to their dependency on claim 49.
Rejections Maintained
Claim Rejections - 35 USC § 102
Claims 36, 39-55 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Domenyuk et al., (WO 2017/161357 A1, published 9/21/2017). The following rejection has been amended due to Applicant’s amendments (12/16/2025).
Regarding claim 36, Domenyuk teaches methods and compositions to identify oligonucleotides that bind targets of interest, where the targets include tissues, cells, circulating biomarkers such as microvesicles, including those derived from various diseases and the oligonucleotides can be used in diagnostic and therapeutic applications (Abstract). Specifically, Domenyuk teaches that the previously described methodology when applied to nucleic acid ligands containing modified nucleotides, incorporates improved characteristics on the ligand, such as improved in vivo stability or improved delivery characteristics (Paragraph 208, lines 10-15).
Further, Domenyuk teaches that the previously described methodology provides a method for identifying binding agents comprising contacting a plurality of extracellular microvesicles with a randomly generated library of binding agents, identifying a subset of the library of binding agents that have an affinity to one or more components of the extracellular microvesicles, where the binding agents may comprise aptamers, antibodies, and/or any other useful type of binding agent disclosed herein or known in the art (Paragraph 368, lines 5-15).
Domenyuk also teaches that the previously described screening methodology as applied to extracellular vesicles includes; a method for identifying a plurality of target ligands comprising, (a) contacting a reference microvesicle population with a plurality of ligands that are capable of binding one or more microvesicle surface markers, (b) isolating a plurality of reference ligands, wherein the plurality of reference ligands comprise a subset of the plurality of ligands that do not have an affinity for the reference microvesicle population; (c) contacting or fusing one or more test microvesicle with the plurality of reference ligands; and (d) identifying a subset of ligands from the plurality of reference ligands that form complexes with a surface markers or barcodes on the one or more test microvesicle, thereby identifying the plurality of target ligands (Paragraph 369, lines 1-10). Specifically, Domenyuk teaches that via the library, the at least one oligonucleotide or the plurality of oligonucleotides can be administered to a subject prior to the detecting, where such a method may allow imaging of at least one cell or tissue in the subject (Paragraph 501, lines 1-5).
Regarding claim 39, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles includes multiple capture binding agents in distinguishable addresses on an array or different wells of an immunoassay plate where the detection binding agents can be against the same antigen as the capture binding agent, or can be directed against other markers (Paragraph 142, lines 10-15). Specifically, Domenyuk teaches that the capture binding agent can be any useful binding agent, i.e., tethered aptamers, antibodies or lectins, and/or the detector antibodies can be similarly substituted, i.e., with detectable or labeled aptamers, antibodies, lectins or other binding proteins or entities (i.e., PMS2) (Table 3; Paragraph 142, lines 10-20).
Regarding claims 40-41, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles can be applied to any useful target or label or barcode, including without limitation a tissue, a cell, an organelle, a protein complex, a lipoprotein, a carbohydrate, a microvesicle, a virus, a membrane fragment, a small molecule, a heavy metal, a toxin, a drug, a nucleic acid, mRNA, microRNA, a protein-nucleic acid complex, and various combinations, fragments and/or complexes of any of these (Paragraph 400, lines 5-10). Further, Domenyuk teaches that the target or label or barcode can be applied via cellular microarrays (also called transfection microarrays), chemical compound microarrays, and carbohydrate arrays (glycoarrays) comprise biochips that provide high-density immobilized arrays of recognition molecules or sequences (i.e., aptamers or antibodies), where biomarker binding is monitored indirectly (i.e., via fluorescence) (Paragraph 150, lines 5-10).
Regarding claim 42, Domenyuk teaches methods and compositions to identify oligonucleotides that bind targets of interest, where the targets include tissues, cells, circulating biomarkers such as microvesicles, including those derived from various diseases and the oligonucleotides can be used in diagnostic and therapeutic applications (Abstract). Specifically, Domenyuk teaches that the previously described methodology when applied to nucleic acid ligands containing modified nucleotides, incorporates improved characteristics on the ligand, such as improved in vivo stability or improved delivery characteristics (Paragraph 208, lines 10-15).
Further, Domenyuk teaches that the previously described methodology provides a method for identifying binding agents comprising contacting a plurality of extracellular microvesicles with a randomly generated library of binding agents, identifying a subset of the library of binding agents that have an affinity to one or more components of the extracellular microvesicles, where the binding agents may comprise aptamers, antibodies, and/or any other useful type of binding agent disclosed herein or known in the art (Paragraph 368, lines 5-15).
Domenyuk also teaches that the previously described screening methodology as applied to extracellular vesicles includes; a method for identifying a plurality of target ligands comprising, (a) contacting a reference microvesicle population with a plurality of ligands that are capable of binding one or more microvesicle surface markers, (b) isolating a plurality of reference ligands, wherein the plurality of reference ligands comprise a subset of the plurality of ligands that do not have an affinity for the reference microvesicle population; (c) contacting or fusing one or more test microvesicle with the plurality of reference ligands; and (d) identifying a subset of ligands from the plurality of reference ligands that form complexes with a surface markers or barcodes on the one or more test microvesicle, thereby identifying the plurality of target ligands (Paragraph 369, lines 1-10). Specifically, Domenyuk teaches that via the library, the at least one oligonucleotide or the plurality of oligonucleotides can be administered to a subject prior to the detecting, where such a method may allow imaging of at least one cell or tissue in the subject (Paragraph 501, lines 1-5).
Regarding claims 43-44, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles can be applied via detecting microvesicles using vesicle surface antigens where a commonly expressed vesicle surface antigen can be CD63, CD9, CD81, CD82, CD37, CD53, Rab-5b, Annexm V or MFG- E8; including tetraspanms, a family of membrane proteins with four transmembrane domains (i.e., CD151, CD53, CD37, CD82, CD81, CD9 and CD63) (Paragraph 135, lines 1-5).
Regarding claim 45, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles includes multiple capture binding agents in distinguishable addresses on an array or different wells of an immunoassay plate where the detection binding agents can be against the same antigen as the capture binding agent, or can be directed against other markers (Paragraph 142, lines 10-15). Specifically, Domenyuk teaches that the capture binding agent can be any useful binding agent, i.e., tethered aptamers, antibodies or lectins, and/or the detector antibodies can be similarly substituted, i.e., with detectable or labeled aptamers, antibodies, lectins or other binding proteins or entities (i.e., PMS2) (Table 3; Paragraph 142, lines 10-20).
Regarding claims 46-47, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles can be applied to any useful target or label or barcode, including without limitation a tissue, a cell, an organelle, a protein complex, a lipoprotein, a carbohydrate, a microvesicle, a virus, a membrane fragment, a small molecule, a heavy metal, a toxin, a drug, a nucleic acid, mRNA, microRNA, a protein-nucleic acid complex, and various combinations, fragments and/or complexes of any of these (Paragraph 400, lines 5-10). Further, Domenyuk teaches that the target or label or barcode can be applied via cellular microarrays (also called transfection microarrays), chemical compound microarrays, and carbohydrate arrays (glycoarrays) comprise biochips that provide high-density immobilized arrays of recognition molecules or sequences (i.e., aptamers or antibodies), where biomarker binding is monitored indirectly (i.e., via fluorescence) (Paragraph 150, lines 5-10).
Regarding claim 48, Domenyuk teaches that the previously described method of screening can be applied to proteins, RNA or DNA as appropriate, which can be circulating freely or in a complex with other biological molecules, and as desired, markers (Table 4) can also be used to detect tumor tissue or for capture and/or detection of vesicles for characterizing phenotypes (Paragraph 136, lines 1-5).
Regarding claim 49, Domenyuk teaches methods and compositions to identify oligonucleotides that bind targets of interest, where the targets include tissues, cells, circulating biomarkers such as microvesicles, including those derived from various diseases and the oligonucleotides can be used in diagnostic and therapeutic applications (Abstract). Specifically, Domenyuk teaches that the previously described methodology when applied to nucleic acid ligands containing modified nucleotides, incorporates improved characteristics on the ligand, such as improved in vivo stability or improved delivery characteristics (Paragraph 208, lines 10-15).
Further, Domenyuk teaches that the previously described methodology provides a method for identifying binding agents comprising contacting a plurality of extracellular microvesicles with a randomly generated library of binding agents, identifying a subset of the library of binding agents that have an affinity to one or more components of the extracellular microvesicles, where the binding agents may comprise aptamers, antibodies, and/or any other useful type of binding agent disclosed herein or known in the art (Paragraph 368, lines 5-15).
Domenyuk also teaches that the previously described screening methodology as applied to extracellular vesicles includes; a method for identifying a plurality of target ligands comprising, (a) contacting a reference microvesicle population with a plurality of ligands that are capable of binding one or more microvesicle surface markers, (b) isolating a plurality of reference ligands, wherein the plurality of reference ligands comprise a subset of the plurality of ligands that do not have an affinity for the reference microvesicle population; (c) contacting or fusing one or more test microvesicle with the plurality of reference ligands; and (d) identifying a subset of ligands from the plurality of reference ligands that form complexes with a surface markers or barcodes on the one or more test microvesicle, thereby identifying the plurality of target ligands (Paragraph 369, lines 1-10). Specifically, Domenyuk teaches that via the library, the at least one oligonucleotide or the plurality of oligonucleotides can be administered to a subject prior to the detecting, where such a method may allow imaging of at least one cell or tissue in the subject (Paragraph 501, lines 1-5).
Regarding claims 50-51, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles can be applied via detecting microvesicles using vesicle surface antigens where a commonly expressed vesicle surface antigen can be CD63, CD9, CD81, CD82, CD37, CD53, Rab-5b, Annexm V or MFG- E8; including tetraspanms, a family of membrane proteins with four transmembrane domains (i.e., CD151, CD53, CD37, CD82, CD81, CD9 and CD63) (Paragraph 135, lines 1-5).
Regarding claim 52, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles includes multiple capture binding agents in distinguishable addresses on an array or different wells of an immunoassay plate where the detection binding agents can be against the same antigen as the capture binding agent, or can be directed against other markers (Paragraph 142, lines 10-15). Specifically, Domenyuk teaches that the capture binding agent can be any useful binding agent, i.e., tethered aptamers, antibodies or lectins, and/or the detector antibodies can be similarly substituted, i.e., with detectable or labeled aptamers, antibodies, lectins or other binding proteins or entities (i.e., PMS2) (Table 3; Paragraph 142, lines 10-20).
Regarding claims 53-54, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles can be applied to any useful target or label or barcode, including without limitation a tissue, a cell, an organelle, a protein complex, a lipoprotein, a carbohydrate, a microvesicle, a virus, a membrane fragment, a small molecule, a heavy metal, a toxin, a drug, a nucleic acid, mRNA, microRNA, a protein-nucleic acid complex, and various combinations, fragments and/or complexes of any of these (Paragraph 400, lines 5-10). Further, Domenyuk teaches that the target or label or barcode can be applied via cellular microarrays (also called transfection microarrays), chemical compound microarrays, and carbohydrate arrays (glycoarrays) comprise biochips that provide high-density immobilized arrays of recognition molecules or sequences (i.e., aptamers or antibodies), where biomarker binding is monitored indirectly (i.e., via fluorescence) (Paragraph 150, lines 5-10).
Regarding claim 55, Domenyuk teaches that the previously described method of screening or identifying extracellular microvesicles can be applied to
Domenyuk teaches each and every limitation of claims 36, 39-55, and therefore Domenyuk anticipates claims 36, 39-55.
Applicant’s Response: The Applicant argues that the amended independent claims, 36, 42, and 49, are not anticipated by Domenyuk because Domenyuk allegedly does not teach a step of comparing quantity ratios of barcode RNAs before and after administration nor using such a comparison to identify a factor influencing extracellular vesicle targeting efficiency, stability or secretion. The Applicant further asserts that Domenyuk does not teach using barcode RNA ration changes for this purpose and therefore fails to disclose the newly added technical features.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully and fully considered but are not found persuasive, as discussed below.
As stated above, the Applicant argues that Domenyuk does not teach a step of comparing a “quantity ratio” of barcode RNAs detected after administration with a corresponding quantity ration prior to administration, nor using such a comparison to identify a factor influencing extracellular vesicle targeting efficiency, stability, or secretion.
As set forth in Domenyuk, the taught screening methodologies include detecting and identifying subsets of ligands, oligonucleotides, or binding agents based on their relative presence, enrichment, or depletion following interaction with extracellular vesicles (Paragraphs 368-369). Further, Domenyuk teaches quantitative detection of binding and biomarker signals using fluorescence or equivalent signal-based readouts (Paragraph 150), which inherently require comparison of signal magnitudes across conditions. Under the broadest reasonable interpretation, a comparison of relative quantities necessarily encompasses a comparison of quantity ratios, even if the term “ratio” is not explicitly used.
Additionally, Domenyuk teaches administering oligonucleotides or libraries to a subject and subsequently detecting and analyzing their distribution or localization in cells, tissues, or biological fluids (Paragraph 501). Comparing detected barcode or ligand signals after administration to reference populations or pre-administration libraries is an inherent aspect of the disclosed screening and selection process (Paragraphs 368-369). Accordingly, the amended limitation requiring comparison of quantity rations before and after administration is disclosed, either expressly or inherently, by Domenyuk.
Further, the Applicant’s argument that Domenyuk does not teach using the comparison to “identify a factor” influencing efficiency, stability, or secretion is likewise unpersuasive. Domenyuk teaches screening methods for identifying ligands, barcodes, or binding agents that preferentially bind, persist, localize, or are enriched in association with extracellular vesicles, and further teaches that such results may be applied to diagnostic and therapeutic applications (Abstract; Paragraphs 368-368, 501). Identifying ligands or barcodes that are enriched or depleted as a result of screening inherently identifying factors influencing extracellular vesicle targeting, stability, or secretion, regardless of whether such factors are labeled using the same terminology as the Applicant.
Moreover, statements in the instant claims directed to identifying a factor that influences efficiency, stability, or secretion merely recite an intended use of result of the disclosed comparison and do not impose additional structural or procedural limitations beyond the comparison itself. Intended use or result language does not distinguish over the prior art where the underlying steps are disclosed. See MPEP 2111.04.
Finally, anticipation does not require that a reference recognize the same problem or articulate the same advantage as the claimed invention. A prior art reference anticipates if it discloses the claimed steps, either expressly or inherently, even if the reference does not describe them in the same terms or for the same stated purpose (see MPEP 2111, 2131). Accordingly, Domenyuk teaches or inherently discloses each limitation of amended claims 36, 42 and 48 under the broadest reasonable interpretation. Therefore, the rejection under 35 USC 102(a)(1) and 102(a)(2) for claims 36, 39-55 is maintained.
Conclusions
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30.
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/ELIZABETH ROSE LAFAVE/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684