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or rejection of record in the previous Office Action, mailed 7/14/2025, which is not addressed in this action has been withdrawn in light of Applicants' amendments and/or arguments. This action is FINAL.
Election/Restriction
Applicant’s election without traverse of Group II in the reply filed on 6/13/2025 is acknowledged. Claims 1-5, 7-10, 12, 14, 16-18, 20, 24-27, 29, 30, 32-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Group 1, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/13/2025.
Claim Status
Applicant amended claims 35-36, 53, 56, 59 and 61 (1/13/2026). Applicant canceled claims 1-34, 39, 41, 43, 49-50, 52, and 54-55 were previously canceled (5/13/2022, 6/13/2025), without prejudice or disclaimer. No new matter was added.
Accordingly, claims 35-38, 40, 42, 44-48, 51, 53, and 56- 61 are under examination (1/13/2026).
Priority
Claims 35-38, 40, 42, 44-48, 51, 53, and 56- 61 receive a priority date of 3/29/2019, the effective filing date of US Provisional Patent 62/826,763.
Objections Withdrawn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The objections to the specification due to the use of a trademark or tradenames are withdrawn in view of Applicant’s amendments.
The objections to the specification due to the use of hyperlinks are withdrawn in view of Applicant’s amendments.
Drawings:
The objections to the Drawings, specifically Figure 15D, due to the lack of a sequence identifier, are withdrawn in view of Applicant’s amendments.
Claims:
The minor formality objections to claims 35, 53, 56, 59 and 61 are withdrawn in view of Applicant’s amendments.
Rejections Withdrawn
Claim Rejections - 35 USC § 112(b)
The rejection of claim 36 under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 2nd paragraph, are withdrawn in view of Applicant’s amendments of claim 35.
Rejections Maintained
Claim Rejections—35 U.S.C. § 102
Claims 35-38, 40, 42, 44-48, 51, 53, and 56-61 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated Bejanin et al., (US PGPub 2005/0119171 A1, published 6/2/2005).
Regarding claim 35, Bejanin teaches methods involving the use of polynucleotide fragments as probes, primers, molecular weight markers and for expressing the polypeptide fragments of the present invention, where fragments include portions of polynucleotides selected from the group consisting of a) polynucleotide sequences of the Sequence Listing, b) genomic GENSET sequences, c) polynucleotides encoding a polypeptide of the present invention, d) sequences of human cDNA clone inserts of the deposited clone pool, and e) polynucleotides encoding the polypeptides encoded by the human cDNA clone inserts of the deposited clone pool (Paragraph 124, lines 1-10). Specifically, Bejanin teaches the application of the previously described involvement of polynucleotide or fusion protein fragments in a kit that may contain an antibody directed against antibodies against one or more of the markers allowing for the condition of an individual to be monitored continuously and the quantified amount of this particular protein measured in the pathological sample can be compared with the amount quantified in a biological sample of a normal individual or with previous samples from the same individual (Paragraph 342, lines 20-25). Bejanin further teaches that the fragmented polypeptide may further be expressed as a fusion protein with a polypeptide signal specifying excretion from the body (Paragraph 634, lines 1-5), and coupled to the cell by introducing a polynucleotide construct (i.e., RNA construct sequence) comprising an expression control element operably linked to the coding sequence (Paragraph 584, lines 1-5).
Bejanin teaches that the previously described continuous cell monitoring method includes an excitation-secretion uncoupling peptide (ESUP) (Paragraph 568, lines 1-5). Further, Bejanin teaches that the selected construct RNA sequence or polynucleotide construct includes any of a wide variety of expression systems can be used to provide the recombinant proteins where suitable expression vehicles include, but are not limited to plasmids, viral particles or baculovirus for insect cells and the expression vehicle can be integrated into the host cell genome (Paragraph 550, lines 10-15). Further, Bejanin teaches that an inducible expression vector can be used to achieve tight controlled expression or capture of the gene in the host cell and recombinant protein can be recovered or retrieved from the host cell and purified by any technique (Paragraph 550, lines 15-20).
Bejanin also teaches a method to purify export vesicles comprising the steps of: i) contacting an antibody specific for the cytoplasmic portion of DOV polypeptide or targeted polynucleotide with a biological sample under conditions that allow antibody binding and ii) removing contaminating materials not bound to the antibody, where such antibody is primarily or secondarily attached to an insoluble matrix or secretion-inducing domain to enable purification (Paragraph 570, lines 1-5). Further, Bejanin teaches vesicle docking results in release of vesicle contents to the extracellular space and harvested at specified times (Paragraph 563, lines 1-5; Paragraph 570, lines 1-5; Paragraph 632, lines 10-15).
Regarding claim 36, Bejanin teaches the previously described method of continuously monitoring live cells, that includes the various liposome-nucleic acid complexes or DNA-RNA complexes that are prepared using methods well known in the art (Paragraph 313, lines 1-5) via amplification of the polynucleotide or RNA molecule through preliminary reverse transcription and synthesis of a second cDNA strand are first performed in order to provide a DNA template to be amplified (Paragraph 1044, lines 1-5). Further, Bejanin teaches that the previously described technique comprises methods for detecting the presence of a polynucleotide of the invention in a sample, the method comprising bringing into contact said sample and a nucleic acid probe or a plurality of nucleic acid probes which hybridize to the polynucleotide, and detecting the hybrid complex formed between said probe or said plurality of probes and said polynucleotide, where the probes can be labeled or barcoded or are immobilized on a substrate (Paragraph 1043, lines 1-10).
Bejanin teaches that through using the previously described duplex methodology, identified labeled or barcoded probes can form a ligand library in recombinant phages, and, following washing, the phages that bind specifically to the targeted protein are either eluted or isolated by a buffer (acid pH) or immunoprecipitated using an antibody specific to the targeted protein (Paragraph 1095, lines 1-5).
Regarding claims 37-38 and 40, Bejanin teaches the previously described method of continuously monitoring live cells, that includes purified or isolated polynucleotide or RNA constructs comprising at least 20 to 400 amino acids (Paragraph 124, lines 5-10).
Bejanin further teaches that epitope-bearing polypeptides of the present invention are used to induce antibodies according to methods well known in the art including, but not limited to, in vivo immunization, in vitro immunization, and phage display methods (Paragraph 207, lines 1-5) and can be applied to a including eukaryotic, prokaryotic, or phage clone (Paragraph 219, lines 10-15).
Regarding claim 42, Bejanin teaches the previously described method of continuously monitoring live cells, that includes amplification of the polynucleotide or RNA molecule through preliminary reverse transcription and synthesis of a second cDNA strand are first performed in order to provide a DNA template to be amplified (Paragraph 1044, lines 1-5). Further, Bejanin teaches that the previously described technique comprises methods for detecting the presence of a polynucleotide of the invention in a sample, the method comprising bringing into contact said sample and a nucleic acid probe or a plurality of nucleic acid probes which hybridize to the polynucleotide, and detecting the hybrid complex formed between said probe or said plurality of probes and said polynucleotide, where the probes can be labeled or barcoded or are immobilized on a substrate (Paragraph 1043, lines 1-10).
Regarding claim 44, Bejanin teaches the previously described method of continuously monitoring live cells, that includes bacterial cells containing a particular clone can be obtained from the composite deposit using standard methods, i.e., by plating a culture of the composite deposit, transferring the lysed colonies to a filter, and hybridizing the filter with a labelled probe such as an oligonucleotide probe specific for the clone of interest (Paragraph 93, lines 1-5). Specifically, Bejanin teaches that a DNA construct or identifying sequence is used that comprises, from 5'-end to 3'-end: a first nucleotide sequence that is found in the library of polypeptide-encoding genomic sequence; a nucleotide sequence comprising a positive selection marker; and a second nucleotide sequence that is found in the GENSET polypeptide-encoding genomic sequence and is located downstream (Paragraph 1077, lines 1-10). Further, Bejanin teaches that a nucleotide sequence of interest or filter sequence is inserted in a targeted location or at a fixed distance the genome harbors at least two loxP sites in the same orientation and located at the respective ends of a nucleotide sequence to be excised from the recombinant genome (Paragraph 1078, lines 1-5).
Regarding claims 45-46, Bejanin teaches the previously described method of continuously monitoring live cells including specified polynucleotides (15-200 bp long) or adaptor sequences that are complementary to targeted binding sites, more preferably to the 5'end or to a splicing donor or acceptor site of the targeted site; where a combination of different antisense polynucleotides complementary to different parts of the desired targeted gene are used (Paragraph 1131, lines 1-5) via a first primer capable of hybridizing to the polyA tail of the targeted site and is hybridized, and a reverse transcription reaction is performed to generate a first cDNA strand (Paragraph 257, lines 1-5).
Specifically, Bejanin teaches that the first cDNA strand is then hybridized to a second primer containing at least 10 consecutive nucleotides of a polynucleotide of the invention and often, the second primer used contains sequences located upstream of the translation initiation site, where the second primer is extended to generate a second cDNA strand complementary to the first cDNA strand (Paragraph 258, lines 1-5).
Regarding claims 47-48 and 51, Bejanin teaches the previously described method of continuously monitoring live cells, that includes bacterial cells containing a particular clone can be obtained from the composite deposit using standard methods, i.e., by plating a culture of the composite deposit, transferring the lysed colonies to a filter, and hybridizing the filter with a labelled probe such as an oligonucleotide probe specific for the clone of interest (Paragraph 93, lines 1-5). Specifically, Bejanin teaches that genomic DNA may be used as a test probe or label to associate that genomic DNA with a particular phenotypic or cell line characteristic displays (Paragraph 271, lines 1-5).
Bejanin teaches the previously described method of continuously monitoring live cells, that includes the various liposome-nucleic acid complexes or DNA-RNA complexes that are prepared using methods well known in the art (Paragraph 313, lines 1-5) via amplification of the polynucleotide or RNA molecule through preliminary reverse transcription and synthesis of a second cDNA strand are first performed in order to provide a DNA template to be amplified (Paragraph 1044, lines 1-5).
Regarding claim 53, Bejanin teaches the previously described method of continuously monitoring live cells, that includes a suitable promoter that may be heterologous with respect to the nucleic acid for which it controls the expression or alternatively can be endogenous to the native polynucleotide containing the coding sequence to be expressed, where promotor regions can be selected from any desired gene using, for example, CAT (chloramphenicol transferase) vectors and more preferably pKK232-8 and pCM7 vectors and preferred bacterial promoters are the LacI, LacZ, the T3 or T7 bacteriophage RNA polymerase promoter (Paragraph 284, lines 1-5).
Regarding claims 56-57, Bejanin teaches methods involving the use of polynucleotide fragments as probes, primers, molecular weight markers and for expressing the polypeptide fragments of the present invention, where fragments include portions of polynucleotides selected from the group consisting of a) polynucleotide sequences of the Sequence Listing, b) genomic GENSET sequences, c) polynucleotides encoding a polypeptide of the present invention, d) sequences of human cDNA clone inserts of the deposited clone pool, and e) polynucleotides encoding the polypeptides encoded by the human cDNA clone inserts of the deposited clone pool (Paragraph 124, lines 1-10). Specifically, Bejanin teaches the application of the previously described involvement of polynucleotide or fusion protein fragments in a kit that may contain an antibody directed against antibodies against one or more of the markers allowing for the condition of an individual to be monitored continuously and the quantified amount of this particular protein measured in the pathological sample can be compared with the amount quantified in a biological sample of a normal individual or with previous samples from the same individual (Paragraph 342, lines 20-25). Bejanin further teaches that the fragmented polypeptide may further be expressed as a fusion protein with a polypeptide signal specifying excretion from the body (Paragraph 634, lines 1-5), and coupled to the cell by introducing a polynucleotide construct (i.e., RNA construct sequence) comprising an expression control element operably linked to the coding sequence (Paragraph 584, lines 1-5), that includes purified or isolated polynucleotide or RNA constructs comprising at least 20 to 400 amino acids (Paragraph 124, lines 5-10).
Bejanin teaches that the previously described continuous cell monitoring method includes an excitation-secretion uncoupling peptide (ESUP) (Paragraph 568, lines 1-5). Further, Bejanin teaches that the selected construct RNA sequence or polynucleotide construct includes any of a wide variety of expression systems can be used to provide the recombinant proteins where suitable expression vehicles include, but are not limited to plasmids, viral particles or baculovirus for insect cells and the expression vehicle can be integrated into the host cell genome (Paragraph 550, lines 10-15). Further, Bejanin teaches that an inducible expression vector can be used to achieve tight controlled expression or capture of the gene in the host cell and recombinant protein can be recovered or retrieved from the host cell and purified by any technique (Paragraph 550, lines 15-20).
Bejanin also teaches a method to purify export vesicles comprising the steps of: I) contacting an antibody specific for the cytoplasmic portion of DOV polypeptide or targeted polynucleotide with a biological sample under conditions that allow antibody binding and ii) removing contaminating materials not bound to the antibody, where such antibody is primarily or secondarily attached to an insoluble matrix or secretion-inducing domain to enable purification (Paragraph 570, lines 1-5). Further, Bejanin teaches vesicle docking results in release of vesicle contents to the extracellular space and harvested at specified times (Paragraph 563, lines 1-5; Paragraph 570, lines 1-5; Paragraph 632, lines 10-15).
Further Bejanin teaches that the previously described method of continuous monitoring of live cells includes preferred expression vectors include viral vectors, especially adenoviral and lentiviral vectors (Paragraph 355, lines 1-5).
Regarding claims 58-59, Bejanin teaches that the previously described method of continuous monitoring of live cells includes a polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA) (Paragraph 120, lines 1-5). Further, Bejanin teaches that the capture domain or acceptor sites encodes a calcium-dependent conformational change that allows the cytoplasmic portion of the polyA binding protein or targeted protein (i.e., DOV) to dock with specific proteins on the plasma membrane (Paragraph 571, lines 1-5).
Regarding claim 60, Bejanin teaches that the previously described method of continuous monitoring of live cells includes selectable markers that confer an identifiable change to the cell permitting easy identification of cells containing the expression construct, where the selectable marker genes for selection of transformed host cells are preferably dihydrofolate reductase or neomycin resistance for eukaryotic cell culture, TRPl for S. cerevisiae or tetracycline (Paragraph 287, lines 1-5).
Regarding claim 61, Bejanin teaches methods involving the use of polynucleotide fragments as probes, primers, molecular weight markers and for expressing the polypeptide fragments of the present invention, where fragments include portions of polynucleotides selected from the group consisting of a) polynucleotide sequences of the Sequence Listing, b) genomic GENSET sequences, c) polynucleotides encoding a polypeptide of the present invention, d) sequences of human cDNA clone inserts of the deposited clone pool, and e) polynucleotides encoding the polypeptides encoded by the human cDNA clone inserts of the deposited clone pool (Paragraph 124, lines 1-10). Specifically, Bejanin teaches the application of the previously described involvement of polynucleotide or fusion protein fragments in a kit that may contain an antibody directed against antibodies against one or more of the markers allowing for the condition of an individual to be monitored continuously and the quantified amount of this particular protein measured in the pathological sample can be compared with the amount quantified in a biological sample of a normal individual or with previous samples from the same individual (Paragraph 342, lines 20-25). Bejanin further teaches that the fragmented polypeptide may further be expressed as a fusion protein with a polypeptide signal specifying excretion from the body (Paragraph 634, lines 1-5), and coupled to the cell by introducing a polynucleotide construct (i.e., RNA construct sequence) comprising an expression control element operably linked to the coding sequence (Paragraph 584, lines 1-5). Further, Bejanin teaches that the capture domain or acceptor sites encodes a calcium-dependent conformational change that allows the cytoplasmic portion of the polyA binding protein or targeted protein (i.e., DOV) to dock with specific proteins on the plasma membrane (Paragraph 571, lines 1-5).
Bejanin teaches that the previously described continuous cell monitoring method includes an excitation-secretion uncoupling peptide (ESUP) (Paragraph 568, lines 1-5). Further, Bejanin teaches that the selected construct RNA sequence or polynucleotide construct includes any of a wide variety of expression systems can be used to provide the recombinant proteins where suitable expression vehicles include, but are not limited to plasmids, viral particles or baculovirus for insect cells and the expression vehicle can be integrated into the host cell genome (Paragraph 550, lines 10-15). Further, Bejanin teaches that an inducible expression vector can be used to achieve tight controlled expression or capture of the gene in the host cell and recombinant protein can be recovered or retrieved from the host cell and purified by any technique (Paragraph 550, lines 15-20).
Bejanin also teaches a method to purify export vesicles comprising the steps of: i) contacting an antibody specific for the cytoplasmic portion of DOV polypeptide or targeted polynucleotide with a biological sample under conditions that allow antibody binding and ii) removing contaminating materials not bound to the antibody, where such antibody is primarily or secondarily attached to an insoluble matrix or secretion-inducing domain to enable purification (Paragraph 570, lines 1-5). Further, Bejanin teaches vesicle docking results in release of vesicle contents to the extracellular space and harvested at specified times (Paragraph 563, lines 1-5; Paragraph 570, lines 1-5; Paragraph 632, lines 10-15).
Bejanin teaches each and every limitation of claims 35-38, 40, 42, 44-48, 51, 53, and 56-61, and therefore Bejanin anticipates claim 35-38, 40, 42, 44-48, 51, 53, and 56-61.
Applicant’s Response: The Applicant argues that Bejanin does not anticipate the independent claims because it fails to disclose a construct RNA sequence capture domain that binds cellular RNA and is exported from the cell as a complex with a fusion protein via a secretion-inducing domain. Further, the Applicant asserts that Bejanin teaches secretion signals and protein export or purification, but does not teach self-assembly of export vesicles containing captured cellular RNA transcripts, nor the claimed dual requirement of RNA capture and vesicle-mediated export.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully and fully considered but are not found persuasive, as discussed below.
The Applicant’s argue that Bejanin fails to disclose a construct RNA sequence capture domain that binds cellular RNA and is exported from the cell as a complex with a fusion protein via a secretion-inducing domain, and further contend that Bejanin does not teach self-assembly of export vesicles containing captured cellular RNA transcripts, as previously stated.
As set forth in Bejanin, the reference teaches continuous monitoring of live cells using polynucleotide constructs and fusion proteins that are expressed in host cells and include signal peptides or secretion-inducing domains directing export of expressed products from the cell (Paragraphs 568, 634). Bejanin further teaches introduction of polynucleotide constructs (i.e. RNA constructs) operably linked to expression control elements into host cells, expression of those constructs, and recovery of nucleic acids or associated products from the extracellular environment at selected time points (Paragraphs 550, 563, 570, 632). Under the broadest reasonable interpretation, the claimed construct RNA sequence capture domain reads on Bejanin’s disclosed polynucleotide probes, adapters, and hybridization-based capture sequences used to bind and detect target RNA or DNA molecules (Paragraphs 313, 1043-1044).
The Applicant’s attempts to distinguish Bejanin on the basis that it allegedly teaches only protein secretion rather than RNA capture and export is unavailing. Anticipation does not require the reference to describe the invention in the same terms used by the Applicants, nor does it require an explicitly recitation of Applicant’s proposed mechanism, so long as the claimed elements are disclosed, either expressly or inherently, in a single reference (see MPEP 2131; In re Schreiber, 128 F. 3s 1473 (Fed. Cir. 1997)). Bejanin teaches hybridization-based capture of polynucleotides, amplification of RNA via reverse transcription, barcoding or labeling of nucleic acids, and recovery of such material following secretion or vesicle release, which collectively meets the claimed limitations when given their broadest reasonable interpretation (Paragraphs 3131, 550, 563, 570, 1043-1044).
Further, in response to the Applicant’s argument that Bejanin fails to teach self-assembly of export vesicles, Bejanin teaches secretion pathways and vesicle-mediated release of cellular contents into the extracellular space, including docking and release of vesicle contents harvested at defined times (Paragraphs 563, 570, 632). The instant claims do not positively require any particular vesicle biogenesis mechanism, nor do they exclude conventional secretion or vesicle pathways as taught by Bejanin. Absent such limiting language, the Applicant’s argument improperly imports features from the specification into the claims, which is inconsistent with examination under the broadest reasonable interpretation (see MPEP 2111).
The Applicant also asserts that Bejanin is silent as to the claimed dual requirement of RNA capture and vesicle-mediated export. However, Bejanin teaches both (i) nucleic acid capture using probes, primers, adapters, and poly(A)-binding interactions, and (ii) secretion or release of expressed constructs or associated products from live cells for downstream detection and analysis (Paragraphs 257, 313, 550, 568, 570). A reference is anticipatory if it discloses all claim limitations arranged as in the claim, even if disclosed across multiple embodiments with the same reference (see MPEP 2131; In re Gleave, 560 F. 3d 1331 (Fed. Cir. 2009)).
Accordingly, Bejanin teaches each and every limitation of the rejected claims, either expressly or inherently, and Applicants have not identified any claim limitation that is absent from the reference when properly construed. The rejection under 35 USC 102(a)(1) and (a)(2) is therefore 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