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 .
Election/Restrictions
Applicants election without traverse of Group 1 (Claims 1-3, 11, 12, 15, 16, 19, 20, 23, 25, 26, 28, 29, 31, 32, 34, 36, and new claims 63-70), drawn to an engineered cell for lentiviral vector production, and species election of SEQ ID NO: 1, in the reply filed on 04/10/2026 is acknowledged. Claims 47 and 54 are withdrawn from consideration, as being directed to a non-elected invention. Claims 1-3, 11, 12, 15, 16, 19, 20, 23, 25, 26, 28, 29, 31, 32, 34, 36, and 63-70 have been examined on the merits.
Priority
Acknowledgement is made that the instant application is a National Stage of International application No. PCT/US2022/026004 (filed 04/22/2022), which claims the benefits of US Provisional Application No. 63/179,129 (filed 04/23/2021).
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.
Claims 1, 3, 34 and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shin et al (US20210062220A1) cited in the IDS filed 01/22/2024.
Shin et al discloses transfecting a mammalian cell with an expression cassette encoding a REV gene under a first promoter, a VSV-G gene under control of a second promoter, and a GAG gene and POL gene under control of a third promoter (See claims 1 and 6). The expression cassettes of Shin et al are integrated chromosomally integrated into the mammalian cell (See ¶0016). Shin et al further discloses each of the promoters in the expression cassette is a de-repressible promoter comprising a functional promoter and a tetracycline operator sequence which is induced by addition of doxycycline (See claim 9 and ¶0062). The cell of Shin et al further comprises an antibiotic resistance selection marker. In one embodiment the selection marker is a Puromycin resistance gene under control of a human phosphoglycerate promoter (See ¶0154 and Fig. 1). In another embodiment the selection marker is a Bleomycin resistance gene under control of the SV40 promoter (See Fig. 2). Exemplary cells of Shin et al include HEK293 and HeLa cells (See ¶0044).
Regarding claims 1 and 3: Shin et al discloses a mammalian cell comprising a chromosomally integrated expression cassette (reads on a stably integrated heterologous polynucleic acid) encoding REV under a first promoter, VSV-G under a second promoter, and GAG and POL under a third promoter (reads on a polycistronic RNA comprising the nucleic acid sequence encoding for Gag and for Pol)which reads an engineered cell comprising integrated heterologous polynucleic acids comprising a nucleic acid sequence encoding for Gag; a nucleic acid sequence encoding for Pol; and a nucleic acid encoding for Rev. Shin et al further discloses each of the promoters is a de-repressible promoter comprising a tetracycline operator sequence which reads on at least one of the promoters is operably linked to a chemically inducible promoter. Furthermore, the expression cassette of Shin et al comprises an antibiotic selection gene under the control of a promoter.
Regarding claim 34: Following the discussion of claim 1 above, Shin et al teaches exemplary mammalian cells can include HEK293 and HeLa cells.
Regarding claim 36: Shin et al discloses the cell of claim 1 (see rejection above) which reads on a kit comprising the engineered cell of claim 1.
Claims 1-3, 11, 12, 15, 16, 19, 20, 23, 34, 36, 63, 64, are 67, are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Xue et al (US20230051793A1), filed 09/16/2020 as evidenced by Addgene #12251, 12253, and 12259.
Xue et al discloses a lentiviral vector producer cell comprising sequences of Gag, Pol, Rev, and VSV-G wherein one or more of the Gag, Pol, Rev, and VSV-G sequences is under control of a Tet-On and/or Cumate inducible expression system (See claim 61). The Tet-On system comprises a TRE3G or TREadv response elements and rtRAadv and rtTA3G transactivators (See ¶0151). Alternatively, the inducible expression system can comprise a Tet-off inducible system (See ¶0021). Gag, Pol, Rev, and VSV-G are stably integrated into the host cell’s genome using a transposon system (See ¶0026). Exemplary cells of Xue et al can comprise HEK293 and BHK cells. The cell production method of Xue uses separate plasmids comprising Gag-Pol, Rev, or VSV-G all of which could be integrated into the same cell (See Tables 4 and 13-14 and Fig. 1). The one or more constructs of Xue et al having Gag/Pol, Rev, VSV-G, a transcription cassette carrying a nucleic acid fragment of interest, and to coding sequence of an activator or repressor protein for the inducible system can further carry a screening gene sequence such as an antibiotic resistance gene that is preferably under the control of an SV40 promoter (See ¶0029). An exemplary plasmid comprising VSV-G further comprises a blasticidin resistance gene (BSD) sequence under the control of an SV40 promoter (See ¶0029 and Fig. 1). Xue et al further discloses introducing transfer-vector cassettes carrying a nucleic acid fragment of interest into the cell. One exemplary gene of interest is a gene encoding for human coagulation factor 8 with a deletion of B protein domain (BDDF8cHA) (See ¶0187, Table 3, and Fig. 1).
Regarding claim 1, 3, and 11: Xue et al discloses a lentiviral vector producer cell comprising stably integrated sequences of Gag, Pol, Rev, and VSV-G wherein one or more of the Gag, Pol, Rev, and VSV-G sequences is under control of a Tet-On and/or Cumate inducible expression system which reads on an engineered cell comprising one or more stably integrated heterologous polynucleic acids collectively comprising: a nucleic acid sequence encoding for Gag; a nucleic acid sequence encoding for Pol; and a nucleic acid encoding for Rev; at least one of which is operably linked to a chemically inducible promoter. Additionally, Xue et al discloses the cells are produced by integrating separate plasmids comprising Gag-Pol, VSV-G, and Rev which reads on a first polynucleic acid comprising the nucleic acid sequence encoding for Gag and Pol, a second polynucleic acid comprising the nucleic acid sequence encoding for VSV-G; and a third polynucleic acid comprising the nucleic acid sequence encoding for Rev.
Regarding claim 2: Following the discussion of claim 1 above, Xue et al discloses the Tet-On system can comprise a promoter with SEQ ID NO: 21 which has 100% similarity to SEQ ID NO: 1 of the instant application. See alignment at end of office action.
Regarding claim 12: Following the discussion of claims 1 and 11 above, Xue et al discloses a plasmid comprising Gag-Pol under control of a Tet-On and/or Cumate inducible expression system which reads on a first expression cassette comprising a nucleic acid sequence of a first chemically inducible promoter; and a nucleic acid sequence encoding for a polycistronic RNA comprising Gag and Pol. Additionally, Xue et al discloses the plasmid comprising Gag and Pol can further comprise a screening gene sequence under control of an SV40 promoter which reads on a selection marker operably linked to a promoter.
Regarding claim 15: Following the discussion of claims 1 and 11 above, Xue et al discloses a plasmid comprising VSV-G under control of a Tet-On and/or Cumate inducible expression system which reads on a second expression cassette comprising a nucleic acid sequence of a second chemically inducible promoter; and a nucleic acid sequence encoding for VSV-G.
Regarding claim 16: Following the discussion of claims 1, 11, and 15 above, Xue et al discloses a plasmid comprising VSV-G under control of a Tet-On and/or Cumate inducible expression system which reads on a second expression cassette comprising a nucleic acid sequence of a second chemically inducible promoter; and a nucleic acid sequence encoding for VSV-G. Xue further discloses the plasmid comprising VSV-G comprises a BSD selection gene under the control of an SV40 promoter which reads on a nucleic acid sequence of a selection marker that is operably linked to a nucleic acid sequence of a promoter.
Regarding claims 19 and 20: Following the discussion of claims 1 and 11 above, Xue et al discloses a plasmid comprising Rev under control of a Tet-On and/or Cumate inducible expression system which reads on a third expression cassette comprising a nucleic acid sequence of a third chemically inducible promoter; and a nucleic acid sequence encoding for Rev. Additionally, Xue et al discloses the plasmid comprising Rev can further comprise a screening gene sequence under control of an SV40 promoter which reads on a selection marker operably linked to a promoter
Regarding claim 23: Following the discussion of claims 1 and 11 above, Xue discloses the cells comprise a Tet-On system comprising TRE3G or TREadv response elements and rtRAadv and rtTA3G transactivators under the control of a CAGGS promoter (See Fig. 1). rtRAadv and rtTA3G read on transcriptional activators that when expressed in the presence of a small molecule inducer, bind to a chemically inducible promoter of the engineered cell.
Regarding claim 34: Following the discussion of claim 1 above, Xue discloses the cells can comprise HEK293 or BHK cells.
Regarding claim 36: Following the discussion of claim 1 above, Xue discloses the cell of claim 1 which reads on a kit comprising the engineered cell of claim 1.
Regarding claims 63, 67, : Following the discussion of claim 1 above, Table 3 of Xue et al discloses a Tet-On protein (i.e. optirtTA3G) having a nucleic acid sequence of SEQ ID NO: 28. The amino acid translation of SEQ ID NO: 28 has a 99.2% similarity to SEQ ID NO: 10 of the instant application (reads on at least 80% identity). Additionally Table 3 of Xue et al discloses a Gag/Pol having a sequence identical to the Gag sequences of Gag/Pol from Addgene #12251, a VSV-G sequence identical to the VSV-G sequence of Addgene #12259, and a Rev sequence identical to the Rev sequence of Addgene #12253. The Gag sequence from Addgene #12251 has 96.8% similarity to SEQ ID NO: 17 of the instant application (reads on at least 80%) and the Pol sequence from Addgene #12251 has 100% similarity to SEQ ID NO: 18 of the instant application. The VSV-G sequence of Addgene #12259 has 100% similarity to SEQ ID NO: 19 of the instant application. The Rev sequence of Addgene #12253 has 100% similarity to SEQ ID NO: 20 of the instant application. See Sequence Alignments at end of office action. Furthermore, Xue discloses one or more of the Gag, Pol, Rev, and VSV-G sequences is under control of a Tet-On thus, in some embodiments all of Gag, Pol, VSV-G, and Rev are operably linked to a promoter capable of being activated by the Tet-On protein.
Regarding claim 64: Following the discussion of claims 1 and 63 above, Xue et al discloses further introducing a nucleic acid comprising a gene of interest (e.g. BDDF8cHA) into the producer cell. The exemplary plasmid comprising BDDF8cHA in Fig. 1 of Xue further comprises a 5’ LTR and a 3’LTR.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-3, 11, 12, 15, 16, 19, 20, 23, 34, 36, 63-67, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Xue et al (US20230051793A1), as evidenced by Addgene #12251, 12253, and 12259 and in view of Bisgrove et al (US9127283B2).
The teachings of Xue et al and Addgene are set forth above.
Xue et al, evidenced by Addgene, anticipates claims 1-3, 11, 12, 15, 16, 19, 20, 23, 34, 36, 63, 64, and 67.
Regarding claims 65 and 66: Following the discussion of claim 1 above, Xue et al discloses a producer cell comprising Gag/Pol, Rev and VSV-G under the control of inducible promoters. The inducible promoter can comprise a Tet-off expression system. Table 3 of Xue et al discloses a Gag/Pol having a sequence identical to the Gag sequences of Gag/Pol from Addgene #12251, a VSV-G sequence identical to the VSV-G sequence of Addgene #12259, and a Rev sequence identical to the Rev sequence of Addgene #12253. The Gag sequence from Addgene #12251 has 96.8% similarity to SEQ ID NO: 17 of the instant application (reads on at least 80%) and the Pol sequence from Addgene #12251 has 100% similarity to SEQ ID NO: 18 of the instant application. The VSV-G sequence of Addgene #12259 has 100% similarity to SEQ ID NO: 19 of the instant application. The Rev sequence of Addgene #12253 has 100% similarity to SEQ ID NO: 20 of the instant application. See Sequence Alignments at end of office action. Furthermore, Xue discloses one or more of the Gag, Pol, Rev, and VSV-G sequences is under control of an inducible system thus, in some embodiments all of Gag, Pol, VSV-G, and Rev are operably linked to a promoter capable of being activated by the Tet-Off protein.
Xue et al does not disclose a sequence for the promoter of a Tet-Off system.
Bisgrove discloses a Tet-Off promoter having SEQ ID NO: 16 which has 100% similarity to SEQ ID NO: 11 of the instant application. See alignment at end of office action.
Given that Xue et al discloses a producer cell comprising Gag/Pol, Rev, and VSV-G under control of a Tet-Off system and Bisgrove discloses a promoter having SEQ ID NO: 16 for a Tet-Off system, it would have been prima facie obvious to substitute the Tet-Off system of Xue et al with the Tet-Off system of Bisgrove, having a promoter with SEQ ID NO: 16, in the cell of Xue et al. One would have expected the Tet-Off system of Bisgrove to work equivocally with the Tet-Off system of Xue et al in the cell of Xue et al because both systems are Tet-Off systems. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Regarding claim 69: Following the discussion of claim 1 above, Xue et al discloses a producer cell comprising Gag/Pol, Rev and VSV-G under the control of an inducible system which can comprise a Tet-Off System. It would have been prima facie obvious to substitute the Tet-Off system of Xue et al with the Tet-Off System of Bisgrove (See rejection of claim 65 above). Additionally, Xue et al discloses examples in which plasmids are transiently transfected (reads on not stably integrated) into the cells in order to optimize the virus producing packaging cells (See Example 6).
Given that Xue et al discloses transiently transfecting cells in order to optimize the virus producing cells, it would have been prima facie obvious to a person or ordinary skill in the art to transiently transfect Plasmids comprising a Tet-Off protein into the producer cells of Xue et al. One would have been motivated to transiently transfect the plasmid into the cells of Xue et al in order to optimize conditions for the cells. There is a reasonable expectation of success because Xue et al teaches examples in which conditions are optimized using transient transfections.
Claims 1-3, 11, 12, 15, 16, 19, 20, 23, 25, 26, 28, 29, 31, 32, 34, 36, and 63-70 are rejected under 35 U.S.C. 103 as being unpatentable over Xue et al (US20230051793A1), as evidenced by Addgene #12251, 12253, and 12259 and in view of Bisgrove et al (US9127283B2) and Shin et al (US20210062220A1).
The teachings of Xue et al, Addgene, Bisgrove et al, and Shin et al are set forth above.
Xue et al, evidenced by Addgene, anticipates claims 1-3, 11, 12, 15, 16, 19, 20, 23, 34, 36, 63, 64, and 67.
Xue et al in view of Bisgrove render claims 1-3, 11, 12, 15, 16, 19, 20, 23, 34, 36, 63-67, and 69 obvious.
Regarding claims 25 and 29 : Following the discussion of claim 1 above, Xue et al discloses a producer cell comprising Gag/Pol, Rev and VSV-G under the control of an inducible system. The system of Xue et al comprises a first stably integrated polynucleic acid comprising sequences encoding for Gag and Pol.
Xue et al does not disclose a single polynucleic acid comprising the sequences of VSV-G and Rev.
Shin et al discloses a polynucleic acid that can be stably integrated into a lentiviral producer cell. The polynucleic acid of Shin et al comprises a REV gene under a first promoter, a VSV-G gene under control of a second promoter, and a GAG gene and POL gene under control of a third promoter. Shin et al further teaches lentiviral production systems utilizing four separate plasmids are labor-intensive (See ¶0004-0009).
Given that Xue et al discloses plasmids for stably integrating Gag/Pol, Rev, and VSV-G into cells for lentiviral production under the control of an inducible promoter system and Shin et al teaches Gag/Pol, Rev, and VSV-G can be combined into the same polynucleotide, it would have been prima facie obvious to a person of ordinary skill in the art to modify the plasmids of Xue et al by including expression cassettes comprising any of Gag/Pol, Rev, and/or VSV-G in the same plasmid in the method of Xue et al in order to simplify integration of the polynucleotide into the producer cell. One would have been motivated to modify the plasmids of Xue et al to comprise any of Gag/Pol, Rev, and/or VSV-G in a single plasmid because Shin et al teaches using separate plasmids is labor-intensive. There is a reasonable expectation of success because Shin et al teaches Gag/Pol, Rev, and VSV-G can be combined into a single plasmid while each is still under the control of its own inducible promoter.
Regarding claim 26: Following the discussion of claims 1 and 25 above, Xue et al discloses a plasmid comprising Gag-Pol under control of a Tet-On and/or Cumate inducible expression system which reads on a first expression cassette comprising a nucleic acid sequence of a first chemically inducible promoter; and a nucleic acid sequence encoding for a polycistronic RNA comprising Gag and Pol.
Regarding claim 28: Following the discussion of claims 1, 25, and 26 above, Xue et al discloses the plasmid comprising Gag and Pol can further comprise a screening gene sequence under control of an SV40 promoter which reads on a selection marker operably linked to a promoter
Regarding claim 31: Following the discussion of claims 1 and 25 above, Xue et al discloses any of the plasmids can further comprise a screening gene sequence under control of an SV40 promoter which reads on a selection marker operably linked to a promoter.
Regarding claim 32: Following the discussion of claims 1 and 25 above, Xue discloses the cells comprise a Tet-On system comprising TRE3G or TREadv response elements and rtRAadv and rtTA3G transactivators under the control of a CAGGS promoter (See Fig. 1). rtRAadv and rtTA3G read on transcriptional activators that when expressed in the presence of a small molecule inducer, bind to a chemically inducible promoter of the engineered cell.
Regarding claims 68 and 70: Following the discussion of claims 1, 36, and 65 above, Xue et al discloses a producer cell comprising Gag/Pol, Rev and VSV-G under the control of an inducible system which can comprise a Tet-Off System. It would have been prima facie obvious to substitute the Tet-Off system of Xue et al with the Tet-Off System of Bisgrove (See rejection of claim 65 above). Xue et al further discloses introducing a nucleic acid comprising a gene of interest (e.g. BDDF8cHA) into the producer cell. The exemplary plasmid comprising BDDF8cHA in Fig. 1 of Xue further comprises a 5’ LTR and a 3’LTR. Additionally, Xue et al discloses examples in which plasmids are transiently transfected (reads on not stably integrated) into the cells in order to optimize the virus producing packaging cells (See Example 6).
Given that Xue et al discloses transiently transfecting cells in order to optimize the virus producing cells, it would have been prima facie obvious to a person or ordinary skill in the art to transiently transfect Plasmids comprising a Tet-Off protein and the BDDF8cHA protein which further comprises 5’ and 3’ LTR sequences into the producer cells of Xue et al. One would have been motivated to transiently transfect the plasmids into the cells of Xue et al in order to optimize conditions for the cells. There is a reasonable expectation of success because Xue et al teaches examples in which conditions are optimized using transient transfections.
Xue et al does not disclose a single polynucleic acid comprising a Tet-Off protein and a gene of interest.
Shin et al teaches combining multiple components required for lentiviral production onto the same plasmid. Shin et al further teaches lentiviral production systems utilizing four separate plasmids are labor-intensive (See ¶0004-0009).
Given that Xue et al discloses plasmids for lentiviral producer cells and Shin et al teaches multiple components for lentiviral production can be combined onto the same plasmid, it would have been prima facie obvious to modify the expression cassettes comprising a Tet-Off protein so that it further comprises a gene of interest along which further comprises a 5’ and 3’ LTR in the method of Xue et al in order to simplify integration of the polynucleotide into the producer cell. One would have been motivated to express both the Tet-Off protein and gene of interest from a single plasmid because Shin et al teaches using separate plasmids is labor-intensive. There is a reasonable expectation of success because Shin et al teaches components for lentiviral producer cells can be combined into the same plasmid.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARISOL ANN O'NEILL/ Examiner, Art Unit 1633
/ALLISON M FOX/ Primary Examiner, Art Unit 1633
Sequence Alignments
Xue et al SEQ ID NO: 21 (Qy) vs. SEQ ID NO: 1 of instant application (DB)
Query Match 100.0%; Score 307; DB 1; Length 346;
Best Local Similarity 100.0%;
Matches 307; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TCCCTATCAGTGATAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGATAGAGAACGAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 12 TCCCTATCAGTGATAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGATAGAGAACGAT 71
Qy 61 GTCGAGTTTACTCCCTATCAGTGATAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 72 GTCGAGTTTACTCCCTATCAGTGATAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGA 131
Qy 121 TAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGATAGAGAACGTATGTCGAGTTTATC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 132 TAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGATAGAGAACGTATGTCGAGTTTATC 191
Qy 181 CCTATCAGTGATAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGATAGAGAACGTATG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 192 CCTATCAGTGATAGAGAACGTATGTCGAGTTTACTCCCTATCAGTGATAGAGAACGTATG 251
Qy 241 TCGAGGTAGGCGTGTACGGTGGGAGGCCTATATAAGCAGAGCTCGTTTAGTGAACCGTCA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 252 TCGAGGTAGGCGTGTACGGTGGGAGGCCTATATAAGCAGAGCTCGTTTAGTGAACCGTCA 311
Qy 301 GATCGCC 307
|||||||
Db 312 GATCGCC 318
translation of Xue et al SEQ ID NO: 28 (Qy) vs. SEQ ID NO: 10 of instant application (DB)
Query Match 99.2%; Score 1289.5; DB 1; Length 249;
Best Local Similarity 99.6%;
Matches 248; Conservative 0; Mismatches 0; Indels 1; Gaps 1;
Qy 1 MSRLDKSKVINSALELLNGVGIEGLTTRKLAQKLGVEQPTLYWHVKNKRALLDALPIEML 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSRLDKSKVINSALELLNGVGIEGLTTRKLAQKLGVEQPTLYWHVKNKRALLDALPIEML 60
Qy 61 DRHHTHSCPLEGESWQDFLRNNAKSYRCALLSHRDGAKVHLGTRPTEKQYE-TLENQLAF 119
||||||||||||||||||||||||||||||||||||||||||||||||||| ||||||||
Db 61 DRHHTHSCPLEGESWQDFLRNNAKSYRCALLSHRDGAKVHLGTRPTEKQYELTLENQLAF 120
Qy 120 LCQQGFSLENALYALSAVGHFTLGCVLEEQEHQVAKEERETPTTDSMPPLLKQAIELFDR 179
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LCQQGFSLENALYALSAVGHFTLGCVLEEQEHQVAKEERETPTTDSMPPLLKQAIELFDR 180
Qy 180 QGAEPAFLFGLELIICGLEKQLKCESGGPTDALDDFDLDMLPADALDDFDLDMLPADALD 239
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QGAEPAFLFGLELIICGLEKQLKCESGGPTDALDDFDLDMLPADALDDFDLDMLPADALD 240
Qy 240 DFDLDMLPG 248
|||||||||
Db 241 DFDLDMLPG 249
Xue et al VSV-G sequence(Addgene #12259) (Qy) vs. SEQ ID NO: 19 of instant application (DB)
Query Match 100.0%; Score 2783; DB 1; Length 511;
Best Local Similarity 100.0%;
Matches 511; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVK 60
Qy 61 MPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTW 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 MPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTW 120
Qy 121 LNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNS 180
Qy 181 TTWHSDYKVKGLCDSNLISMDITFFSEDGELSSLGKEGTGFRSNYFAYETGGKACKMQYC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TTWHSDYKVKGLCDSNLISMDITFFSEDGELSSLGKEGTGFRSNYFAYETGGKACKMQYC 240
Qy 241 KHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 KHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLC 300
Qy 301 QETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMV 360
Qy 361 GMISGTTTERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GMISGTTTERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQV 420
Qy 421 FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFL 480
Qy 481 VLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK 511
|||||||||||||||||||||||||||||||
Db 481 VLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK 511
Xue et al GAG sequence(Addgene #12251) (Qy) vs. SEQ ID NO: 17 of instant application (DB)
Query Match 96.8%; Score 2234.5; DB 1; Length 432;
Best Local Similarity 99.3%;
Matches 429; Conservative 0; Mismatches 0; Indels 3; Gaps 3;
Qy 1 MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQI 60
Qy 61 LGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQ-AA 119
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||
Db 61 LGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAA 120
Qy 120 DTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGA- 178
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT 180
Qy 179 PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPV-AGPIAPGQMREPRGSDIAGTT 237
|||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||
Db 181 PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTT 240
Qy 238 STLQEQIGWMTHNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF 297
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 STLQEQIGWMTHNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF 300
Qy 298 YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKA 357
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKA 360
Qy 358 RVLAEAMSQVTNPATIMIQKGNFRNQRKTVKCFNCGKEGHIAKNCRAPRKKGCWKCGKEG 417
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 RVLAEAMSQVTNPATIMIQKGNFRNQRKTVKCFNCGKEGHIAKNCRAPRKKGCWKCGKEG 420
Qy 418 HQMKDCTERQAN 429
||||||||||||
Db 421 HQMKDCTERQAN 432
Xue et al POL sequence(Addgene #12251) (Qy) vs. SEQ ID NO: 18 of instant application (DB)
Query Match 100.0%; Score 4852; DB 1; Length 1003;
Best Local Similarity 100.0%;
Matches 912; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92 MNLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGC 151
Qy 61 TLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 152 TLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPY 211
Qy 121 NTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKQKKSVTVLDVGDAYF 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 212 NTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKQKKSVTVLDVGDAYF 271
Qy 181 SVPLDKDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQCSMTKILEPFRKQNP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 272 SVPLDKDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQCSMTKILEPFRKQNP 331
Qy 241 DIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGFTTPDKKHQKEPPFLWMGYELHP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 332 DIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGFTTPDKKHQKEPPFLWMGYELHP 391
Qy 301 DKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQIYAGIKVRQLCKLLRGTKALTEVVPLT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 392 DKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQIYAGIKVRQLCKLLRGTKALTEVVPLT 451
Qy 361 EEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYAR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 452 EEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYAR 511
Qy 421 MKGAHTNDVKQLTEAVQKIATESIVIWGKTPKFKLPIQKETWEAWWTEYWQATWIPEWEF 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 512 MKGAHTNDVKQLTEAVQKIATESIVIWGKTPKFKLPIQKETWEAWWTEYWQATWIPEWEF 571
Qy 481 VNTPPLVKLWYQLEKEPIIGAETFYVDGAANRETKLGKAGYVTDRGRQKVVPLTDTTNQK 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 572 VNTPPLVKLWYQLEKEPIIGAETFYVDGAANRETKLGKAGYVTDRGRQKVVPLTDTTNQK 631
Qy 541 TELQAIHLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVSQIIEQLIKKEKVYLAWV 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 632 TELQAIHLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVSQIIEQLIKKEKVYLAWV 691
Qy 601 PAHKGIGGNEQVDKLVSAGIRKVLFLDGIDKAQEEHEKYHSNWRAMASDFNLPPVVAKEI 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 692 PAHKGIGGNEQVDKLVSAGIRKVLFLDGIDKAQEEHEKYHSNWRAMASDFNLPPVVAKEI 751
Qy 661 VASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQE 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 752 VASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQE 811
Qy 721 TAYFLLKLAGRWPVKTVHTDNGSNFTSTTVKAACWWAGIKQEFGIPYNPQSQGVIESMNK 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 812 TAYFLLKLAGRWPVKTVHTDNGSNFTSTTVKAACWWAGIKQEFGIPYNPQSQGVIESMNK 871
Qy 781 ELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQ 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 872 ELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQ 931
Qy 841 ITKIQNFRVYYRDSRDPVWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 932 ITKIQNFRVYYRDSRDPVWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMA 991
Qy 901 GDDCVASRQDED 912
||||||||||||
Db 992 GDDCVASRQDED 1003
Xue et al REV sequence(Addgene #12253) (Qy) vs. SEQ ID NO: 20 of instant application (DB)
Query Match 100.0%; Score 601; DB 1; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAGRSGDSDEDLLKAVRLIKFLYQSNPPPNPEGTRQARRNRRRRWRERQRQIHSISERIL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAGRSGDSDEDLLKAVRLIKFLYQSNPPPNPEGTRQARRNRRRRWRERQRQIHSISERIL 60
Qy 61 STYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQILVESPTILESGAKE 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 STYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQILVESPTILESGAKE 116
SEQ ID NO: 11 of instant application (Qy) vs. SEQ ID NO: 16 of Bisgrove (DB)
Query Match 100.0%; Score 1300; Length 248;
Best Local Similarity 100.0%;
Matches 248; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSRLDKSKVINSALELLNEVGIEGLTTRKLAQKLGVEQPTLYWHVKNKRALLDALAIEML 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSRLDKSKVINSALELLNEVGIEGLTTRKLAQKLGVEQPTLYWHVKNKRALLDALAIEML 60
Qy 61 DRHHTHFCPLEGESWQDFLRNNAKSFRCALLSHRDGAKVHLGTRPTEKQYETLENQLAFL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRHHTHFCPLEGESWQDFLRNNAKSFRCALLSHRDGAKVHLGTRPTEKQYETLENQLAFL 120
Qy 121 CQQGFSLENALYALSAVGHFTLGCVLEDQEHQVAKEERETPTTDSMPPLLRQAIELFDHQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CQQGFSLENALYALSAVGHFTLGCVLEDQEHQVAKEERETPTTDSMPPLLRQAIELFDHQ 180
Qy 181 GAEPAFLFGLELIICGLEKQLKCESGGPADALDDFDLDMLPADALDDFDLDMLPADALDD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GAEPAFLFGLELIICGLEKQLKCESGGPADALDDFDLDMLPADALDDFDLDMLPADALDD 240
Qy 241 FDLDMLPG 248
||||||||
Db 241 FDLDMLPG 248
Prosecution Insights