Prosecution Insights
Last updated: April 19, 2026
Application No. 18/217,863

TRANSPOSON-BASED VECTORS AND USES

Non-Final OA §103§DP
Filed
Jul 03, 2023
Examiner
BATES, KEENAN ALEXANDER
Art Unit
1631
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Just-Evotec Biologics Inc.
OA Round
1 (Non-Final)
46%
Grant Probability
Moderate
1-2
OA Rounds
3y 3m
To Grant
99%
With Interview

Examiner Intelligence

Grants 46% of resolved cases
46%
Career Allow Rate
25 granted / 54 resolved
-13.7% vs TC avg
Strong +71% interview lift
Without
With
+70.8%
Interview Lift
resolved cases with interview
Typical timeline
3y 3m
Avg Prosecution
88 currently pending
Career history
142
Total Applications
across all art units

Statute-Specific Performance

§101
6.3%
-33.7% vs TC avg
§103
31.9%
-8.1% vs TC avg
§102
24.3%
-15.7% vs TC avg
§112
28.3%
-11.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 54 resolved cases

Office Action

§103 §DP
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 Applicant’s election without traverse of Group I (Claims 1 -17 ; drawn to a recombinant expression vector and a mammalian cell comprising the vector ) in the reply filed on January 19 , 202 6 , is acknowledged. Claims 18-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Groups II and III), there being no allowable generic or linking claim. Applicant further elected the following species: a. SEQ ID NO: 46 as the sequence for the deleted SV40 promoter b. glutamine synthetase as the selectable marker In light of the Applicant’s elected species, claim 6 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. DETAILED ACTION The claims filed on July 3 , 202 3 , have been acknowledged. In light of the Applicant’s elected invention and species, claims 6 and 18-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-5 and 7-17 are pending and examined on the merits. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc. , 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed applications, Application No. 62/ 388 , 391, filed January 27, 2016, Application No. PCT/US2017/015130 , filed on January 26, 2017, Application No. 16/072,180, filed on July 24, 2018, Application No. 16/286,551, February 26, 2019 , and Application No. 17190954 , filed on March 3, 2021, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. These provisional applications do not provide information related to a recombinant expression vector, comprising: a first expression cassette, comprising: ( i ) a control sequence comprising: (A) a murine cytomegalovirus ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a human cytomegalovirus ( huCMV ) intron A sequence . None of the prior Applications recite the use of a huCMV intron A sequence as part of the recombinant vectors. In the instant Application, the huCMV intron A sequence is identified in Figures 31-36 a nd paragraphs 0023, 0025, 0028, 0259, 0262-0264, and 0346. These Figures and paragraphs are not included in any of the previous applications. Therefore, claims 1- 5 and 7- 17 do not receive domestic benefit from any of the previously filed applications. As such, claims 1- 5 and 7- 17 receive an effective filing date based on the filing date of the instant application, filed on July 3, 2023 . Information Disclosure Statement The information disclosure statements (IDS) filed on October 18 , 2023, have been considered. Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis ( i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . Claims 1- 5 and 7- 17 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 20220177916 (McGrew) and further in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay). Regarding claim s 1 and 12 , McGrew teaches a recombinant expression vector, compris ing : (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application) ; (b) a first expression cassette, comprising: ( i ) a control sequence comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence of the first promoter; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the control sequence; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame; ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) ( paragraphs 0031-0039) . McGrew does not teach wherein the recombinant vector comprises a human CMV intron A sequence. However, Gay teaches that that the activity of the h uman CMV promoter can be increased by inserting intron A of the major immediate early gene of the human cytomegalovirus . Gay teaches a mammalian expression vector comprising a murine CMV promoter and the first intron of t he major immediate early gene of the human cytomegalovirus (first hCMV intron) operably linked to a heterologous gene sequence encoding a desired recombinant protein. The mCMV promoter plus the first hCMV intron located downstream of the mCMV promoter form a regulatory unit which drives the expression of the downstream coding sequence. T he present vector comprising within the expression cassette the mCMV promoter in combination with the first hCMV intron drives the expression of heterologous protein products at levels higher than those seen for vectors only containing the mCMV promoter (page 2, paragraph 3-page 3, paragraph 3) . It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the EF1 α intron of the recombinant expression vector of McGrew with the human CMV intron A of Gay to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Gay teaches that that the activity of the human and mouse CMV promoter can be increased by inserting human CMV intron A into the expression vector downstream of the promoter. Therefore, it would have been obvious that one could replace the EF1 α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claim s 2 -4 and 13-14 , McGrew teaches that the vector can further compris e : (e) a third expression cassette comprising: ( i ) a control sequence comprising an inducible promoter comprising one or more TetO sequences; (ii) an open reading frame encoding a protein of interest operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV-P sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence (paragraphs 0300-0320) . Regarding claim 3 and 13, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 5 and 7, McGrew teaches that the weak constitutive promoter is a deleted SV 40 promoter and wherein the deleted SV40 promoter comprises the nucleotide sequence of SEQ ID NO:46 (which has 100% sequence identity to SEQ ID NO: 46 of the instant application ( paragraphs 0263-0265). Regarding claims 8-10, McGrew teaches that the selectable marker can be glutamine synthetase encoded by the nucleotide sequence of SEQ ID NO: 49 (which has 100% sequence identity to SEQ ID NO: 49 of the instant application) (paragraphs 0266-0268). Regarding claim 11, McGrew teaches that the polyadenylation sequence can be from a SV40 late polyadenylation (paragraph 0132). Regarding claims 15-17, McGrew teaches a mammalian host cell comprising the expression vector, wherein the host cells is a CHO-K1 cell (paragraphs 0213-0298). 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 . Claim s 1- 5 and 7- 17 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim s 1-29 of U.S. Patent No. 11028410 in view of United States Patent Application No. 20220177916 (McGrew) and World Intellectual Property Organization Patent Application No. 2006111387 (Gay). Regarding claim s 1 and 12 , ‘410 claims a recombinant expression vector comprising an expression cassette, comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- 1 alpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the promoter ; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame (claims 1, 8, and 14 -15 ). ‘410 is silent regarding the overall construction of the recombinant expression vector. However, McGrew teaches a recombinant expression vector, compris ing : (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application) ; (b) a first expression cassette, comprising: ( i ) a control sequence comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence of the first promoter; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the control sequence; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame; ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) ( paragraphs 0031-0039) . McGrew teaches that the vector can further comprise: (e) a third expression cassette comprising: ( i ) a control sequence comprising an inducible promoter comprising one or more TetO sequences; (ii) an open reading frame encoding a protein of interest operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV-P sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence (paragraphs 0300-0320). McGrew teaches that the weak constitutive promoter is a deleted SV 40 promoter and wherein the deleted SV40 promoter comprises the nucleotide sequence of SEQ ID NO:46 (which has 100% sequence identity to SEQ ID NO: 46 of the instant application (paragraphs 0263-0265). McGrew teaches that the selectable marker can be glutamine synthetase encoded by the nucleotide sequence of SEQ ID NO: 49 (which has 100% sequence identity to SEQ ID NO: 49 of the instant application) (paragraphs 0266-0268). McGrew teaches that the polyadenylation sequence can be from a SV40 late polyadenylation (paragraph 0132). As McGrew shows the same expression cassette of ‘410 can be included in a recombinant expression vector with piggybac ITRs and a second and third expression cassette, it would have been obvious that the expression cassette of ‘410 could be included in a larger recombinant expression vector, as outlined in McGrew. The combined teachings of ‘410 and McGrew do not teach wherein the recombinant vector comprises a human CMV intron A sequence. However, Gay teaches that that the activity of the human CMV promoter can be increased by inserting intron A of the major immediate early gene of the human cytomegalovirus. Gay teaches a mammalian expression vector comprising a murine CMV promoter and the first intron of the major immediate early gene of the human cytomegalovirus (first hCMV intron) operably linked to a heterologous gene sequence encoding a desired recombinant protein. The mCMV promoter plus the first hCMV intron located downstream of the mCMV promoter form a regulatory unit which drives the expression of the downstream coding sequence. The present vector comprising within the expression cassette the mCMV promoter in combination with the first hCMV intron drives the expression of heterologous protein products at levels higher than those seen for vectors only containing the mCMV promoter (page 2, paragraph 3-page 3, paragraph 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the EF1α intron of the recombinant expression vector of ‘410 and McGrew with the human CMV intron A of Gay to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Gay teaches that that the activity of the human and mouse CMV promoter can be increased by inserting human CMV intron A into the expression vector downstream of the promoter. Therefore, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 2-4 and 13-14, McGrew , as stated supra, teaches that the vector can further comprise: (e) a third expression cassette comprising: ( i ) a control sequence comprising an inducible promoter comprising one or more TetO sequences; (ii) an open reading frame encoding a protein of interest operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV-P sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence (paragraphs 0300-0320). Regarding claim 3 and 13, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 5 and 7, McGrew , as stated supra, teaches that the weak constitutive promoter is a deleted SV 40 promoter and wherein the deleted SV40 promoter comprises the nucleotide sequence of SEQ ID NO:46 (which has 100% sequence identity to SEQ ID NO: 46 of the instant application (paragraphs 0263-0265). Regarding claims 8-10, McGrew , as stated supra, teaches that the selectable marker can be glutamine synthetase encoded by the nucleotide sequence of SEQ ID NO: 49 (which has 100% sequence identity to SEQ ID NO: 49 of the instant application) (paragraphs 0266-0268). Regarding claim 11, McGrew , as stated supra, teaches that the polyadenylation sequence can be from a SV40 late polyadenylation (paragraph 0132). Regarding claims 15-17, ‘410 claims a mammalian host cell comprising the expression vector, wherein the host cells is a CHO-K1 cell (claims 16-19) and McGrew teaches a mammalian host cell comprising the expression vector, wherein the host cells is a CHO-K1 cell (paragraphs 0213-0298). Claims 1 - 5, 7-10, and 15- 17 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1- 13 of U.S. Patent No. 11098310 in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay). Regarding claim 1, ‘310 claims a recombinant expression vector, compris ing : (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application) ; (b) a first expression cassette, comprising: ( i ) a control sequence comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the control sequence; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame; ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) ( claim 1 ) . ‘310 does not claim wherein the recombinant vector comprises a human CMV intron A sequence. However, Gay teaches that that the activity of the h uman CMV promoter can be increased by inserting intron A of the major immediate early gene of the human cytomegalovirus . Gay teaches a mammalian expression vector comprising a murine CMV promoter and the first intron of t he major immediate early gene of the human cytomegalovirus (first hCMV intron) operably linked to a heterologous gene sequence encoding a desired recombinant protein. The mCMV promoter plus the first hCMV intron located downstream of the mCMV promoter form a regulatory unit which drives the expression of the downstream coding sequence. T he present vector comprising within the expression cassette the mCMV promoter in combination with the first hCMV intron drives the expression of heterologous protein products at levels higher than those seen for vectors only containing the mCMV promoter (page 2, paragraph 3-page 3, paragraph 3) . It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the EF1 α intron of the recombinant expression vector of ‘310 with the human CMV intron A of Gay to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Gay teaches that that the activity of the human and mouse CMV promoter can be increased by inserting human CMV intron A into the expression vector downstream of the promoter. Therefore, it would have been obvious that one could replace the EF1 α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 2-4, McGrew teaches that the vector can further comprise: (e) a third expression cassette comprising: ( i ) a control sequence comprising a promoter; (ii) an open reading frame encoding a protein of interest operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence ( claims 2-3 ). Regarding claim 3, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 5 and 7, ‘310 claims that the weak constitutive promoter is a deleted SV 40 promoter and wherein the deleted SV40 promoter comprises the nucleotide sequence of SEQ ID NO:46 (which has 100% sequence identity to SEQ ID NO: 46 of the instant application ( claims 4 and 6 ). Regarding claims 8-10, ‘310 claims that the selectable marker can be glutamine synthetase encoded by the nucleotide sequence of SEQ ID NO: 49 (which has 100% sequence identity to SEQ ID NO: 49 of the instant application) ( claims 7-9 ). Regarding claims 15-17, ‘310 claims a mammalian host cell comprising the expression vector, wherein the host cells is a CHO-K1 cell ( claims 10-12 ). Claims 1 , 3- 4 and 11-14 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-13 of U.S. Patent No. 11098310 in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay) as applied to claims 1 and 3 -4 above, and further in view of United States Patent Application No. 20220177916 (McGrew) . T he teachings of ‘310 and Gay are as discussed above. ‘310 does not teach wherein the polyadenylation site is an SV40 late polyadenylation site nor wherein the promoter sequence contains one or more TetO sequences. However, McGrew teaches a recombinant expression vector, compris ing : (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application) ; (b) a first expression cassette, comprising: ( i ) a control sequence comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence of the first promoter; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the control sequence; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame; ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) (paragraphs 0031-0039) . McGrew teaches that the vector can further comprise: (e) a third expression cassette comprising: ( i ) a control sequence comprising an inducible promoter comprising one or more TetO sequences; (ii) an open reading frame encoding a protein of interest operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV-P sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence (paragraphs 0300-0320). McGrew teaches that the SV40 polyadenylation sequence can be from a SV40 late polyadenylation (paragraph 0132). As McGrew teaches the same expression vector of ‘310 and directly identifies the SV40 late polyadenylation sequence as an option for use in their vector, it would have been obvious that this sequence could also be used in the similar expression vector of ‘310. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding the TetO sequences, it would have been obvious that the expression vector of ‘310 could be modified to include TetO sequences in their promoter sequences as McGrew teaches the same expression vector of ‘310 and directly identifies that this expression vector can be modified to include TetO sequences. Therefore, McGrew has successfully reduced to practice that the expression vector of ‘310 can be modified to include TetO sequences in the promoter. One of ordinary skill in the art would want to make this modification because TetO sequences allow for inducible control of the expression of the protein of interest. This allows for greater control of the expression of the protein of interest. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Claims 1-5 , 7- 10, and 12- 17 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1- 13 of U.S. Patent No. 11261462 in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay). Regarding claim s 1 and 12 , ‘ 462 claims a recombinant expression vector comprising an expression cassette, comprising: (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application); (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- 1 alpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the promoter ; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) ( claim 1 ) . ‘462 does not teach wherein the recombinant vector comprises a human CMV intron A sequence. However, Gay teaches that that the activity of the human CMV promoter can be increased by inserting intron A of the major immediate early gene of the human cytomegalovirus. Gay teaches a mammalian expression vector comprising a murine CMV promoter and the first intron of the major immediate early gene of the human cytomegalovirus (first hCMV intron) operably linked to a heterologous gene sequence encoding a desired recombinant protein. The mCMV promoter plus the first hCMV intron located downstream of the mCMV promoter form a regulatory unit which drives the expression of the downstream coding sequence. The present vector comprising within the expression cassette the mCMV promoter in combination with the first hCMV intron drives the expression of heterologous protein products at levels higher than those seen for vectors only containing the mCMV promoter (page 2, paragraph 3-page 3, paragraph 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the EF1α intron of the recombinant expression vector of ‘462 with the human CMV intron A of Gay to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Gay teaches that that the activity of the human and mouse CMV promoter can be increased by inserting human CMV intron A into the expression vector downstream of the promoter. Therefore, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 2-4 and 13-14, ‘462 claims that the vector can further comprise: (e) a third expression cassette comprising: ( i ) a control sequence comprising an inducible promoter comprising one or more TetO sequences; (ii) an open reading frame encoding a protein of interest operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV-P sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence ( claims 2-3 ). Regarding claim 3 and 13, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 5 and 7, ‘462 claims that the weak constitutive promoter is a deleted SV 40 promoter and wherein the deleted SV40 promoter comprises the nucleotide sequence of SEQ ID NO:46 (which has 100% sequence identity to SEQ ID NO: 46 of the instant application ( claims 4 and 6 ). Regarding claims 8-10, ‘462 claims that the selectable marker can be glutamine synthetase encoded by the nucleotide sequence of SEQ ID NO: 49 (which has 100% sequence identity to SEQ ID NO: 49 of the instant application) ( claims 7-9 ). Regarding claims 15-17, ‘ 462 claims a mammalian host cell comprising the expression vector, wherein the host cells is a CHO-K1 cell (claims 10-12 ) . Claims 1 and 11 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-13 of U.S. Patent No. 11261462 in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay) as applied to claim 1 above, and further in view of United States Patent Application No. 20220177916 (McGrew) . The teachings of ‘ 462 and Gay are as discussed above. ‘ 462 does not teach wherein the polyadenylation site is an SV40 late polyadenylation site . However, McGrew teaches a recombinant expression vector, compris ing : (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application) ; (b) a first expression cassette, comprising: ( i ) a control sequence comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence of the first promoter; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the control sequence; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame; ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) (paragraphs 0031-0039) . McGrew teaches that the SV40 polyadenylation sequence can be from a SV40 late polyadenylation (paragraph 0132). As McGrew teaches the same expression vector of ‘ 462 and directly identifies the SV40 late polyadenylation sequence as an option for use in their vector, it would have been obvious that this sequence could also be used in the similar expression vector of ‘ 462 . Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Claims 1-5 and 7-17 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-13 of U.S. Patent No. 11685933 in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay) and United States Patent Application No. 20220177916 (McGrew) . Regarding claim s 1 -4 and 12 -14 , ‘ 933 claims a recombinant expression vector comprising an expression cassette, comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- 1 alpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a first immunoglobulin subunit operably linked to the control sequence ; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame ( b ) a second expression cassette comprising: ( i ) a control sequence comprising an inducible promoter comprising one or more TetO sequences; (ii) an open reading frame encoding a second immunoglobulin subunit operably linked to the control sequence; and (iii) a second polyadenylation site operably linked 3' to the open reading frame wherein the control sequence ( i ) of the third expression cassette comprises: (1) a mCMV enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV-P sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF- lalpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF -1 alpha intron sequence (claims 1 -3). ( d ) a third expression cassette, comprising: ( i ) a weak constitutive promoter, operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame ( claims 1-3 ). ‘ 933 does not teach wherein the recombinant vector comprises a human CMV intron A sequence. However, Gay teaches that that the activity of the human CMV promoter can be increased by inserting intron A of the major immediate early gene of the human cytomegalovirus. Gay teaches a mammalian expression vector comprising a murine CMV promoter and the first intron of the major immediate early gene of the human cytomegalovirus (first hCMV intron) operably linked to a heterologous gene sequence encoding a desired recombinant protein. The mCMV promoter plus the first hCMV intron located downstream of the mCMV promoter form a regulatory unit which drives the expression of the downstream coding sequence. The present vector comprising within the expression cassette the mCMV promoter in combination with the first hCMV intron drives the expression of heterologous protein products at levels higher than those seen for vectors only containing the mCMV promoter (page 2, paragraph 3-page 3, paragraph 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the EF1α intron of the recombinant expression vector of ‘ 933 with the human CMV intron A of Gay to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Gay teaches that that the activity of the human and mouse CMV promoter can be increased by inserting human CMV intron A into the expression vector downstream of the promoter. Therefore, it would have been obvious that one could replace the EF1α intron with a human CMV intron A as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. The combined teachings of ‘933 and Gay do not teach using piggyback ITRs. However, However, McGrew teaches a recombinant expression vector, comprising: (a) a 5' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO:45 (which is 100% identical to SEQ ID NO: 45 of the instant application); (b) a first expression cassette, comprising: ( i ) a control sequence comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- lalpha intron sequence, comprising one or more TetO sequences inserted within the CMV promoter sequence of the first promoter; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a protein of interest operably linked to the control sequence; and ( iii ) a polyadenylation site operably linked 3 ' to the open reading frame; ( c ) a second expression cassette, comprising: ( i ) a weak constitutive promoter , operably linked to an open reading frame encoding a selectable marker; and ( ii ) a polyadenylation site operably linked 3' to the open reading frame; and ( d ) a 3 ' PiggyBac ITR comprising the nucleotide sequence of SEQ ID NO : 47 (which has 100% sequence identity to SEQ ID NO: 47 of the instant application) (paragraphs 0031-0039). As McGrew teaches the same expression vector of ‘ 933 and directly identifies the piggybac ITRs of sequences of SEQ ID NOs: 45 and 47 as an option for use in their vector, it would have been obvious that these sequence s could also be used in the similar expression vector of ‘ 933 . Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claim 3 and 13, it would have been obvious that one could replace the EF1α intron with a human CMV intron A in the second expression cassette as human CMV intron A was known to increase the activity of the human and mouse promoter when included in an expression vector. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 5 and 7, ‘ 933 claims that the weak constitutive promoter is a deleted SV 40 promoter and wherein the deleted SV40 promoter comprises the nucleotide sequence of SEQ ID NO:46 (which has 100% sequence identity to SEQ ID NO: 46 of the instant application (claims 4 and 6). Regarding claims 8-10, ‘ 933 claims that the selectable marker can be glutamine synthetase encoded by the nucleotide sequence of SEQ ID NO: 49 (which has 100% sequence identity to SEQ ID NO: 49 of the instant application) (claims 7-9). Regarding claim 11, McGrew teaches that the SV40 polyadenylation sequence can be from a SV40 late polyadenylation (paragraph 0132). As McGrew teaches the same expression vector of ‘ 933 and directly identifies the SV40 late polyadenylation sequence as an option for use in their vector, it would have been obvious that this sequence could also be used in the similar expression vector of ‘462. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success. Regarding claims 15-17, ‘ 933 claims a mammalian host cell comprising the expression vector, wherein the host cells is a CHO-K1 cell (claims 10-12). Claims 1-5 and 7-17 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-13 of U.S. Patent No. 11692193 in view of World Intellectual Property Organization Patent Application No. 2006111387 (Gay) and United States Patent Application No. 20220177916 (McGrew) . Regarding claim s 1 -4 and 12-14 , ‘ 193 claims a recombinant expression vector comprising an expression cassette, comprising: (1) a murine CMV ( mCMV ) enhancer sequence, comprising a mCMV enhancer element ( mCMV -E) and a CMV promoter (CMV-P) sequence at its 3' end, operably linked 5' to a rat EF- 1 alpha intron sequence; (2) an intervening first leader sequence operably linked, 3' to the CMV-P sequence of the mCMV enhancer sequence, and 5' to the rat EF-1 alpha intron sequence; and (3) a second leader sequence operably linked 3' to the rat EF-1 alpha intron sequence; ( ii ) an open reading frame encoding a first immunoglobulin subunit operably linked to the control sequence ; and ( iii ) a polyadenylation
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Prosecution Timeline

Jul 03, 2023
Application Filed
Mar 27, 2026
Non-Final Rejection — §103, §DP (current)

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3y 3m
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