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 .
DETAILED ACTION
This Non-Final Office Action is responsive to the communication received 10/28/2022.
Claims 1-20 are pending.
Claims 1-20 are under examination in this Office Action.
Claim Rejections - 35 USC § 103(a)
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103(a) 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.
5. Secondary considerations (objective evidence of nonobviousness): a) commercial success; b) long felt need; c) evidence of unexpected results; d) skepticism of experts; and e) copying.
Common Ownership of Claimed Invention Presumed
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the Examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the Examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Sclimenti et al (12/15/2001) Nucleic Acids Research volume 29 pages 5044 to 5051 (hereinafter known as "Sclimenti") in view of Carlos et al. (05/21/2015) US Patent Application Publication 2015/0140665 A1 (hereinafter known as "Carlos") and Payne et al. (11/08/2018) US Patent Application Publication 2018/0319850 A1 (hereinafter known as "Payne").
With regards to claims 1, 5-6 and 10-12, Sclimenti teaches:
a) as in claims 1, 5-6 and 10-12, a method comprising: (1) obtaining a first plurality of mammalian cells each of which comprises at a genomic locus a first recombination site recognized by a serine integrase, and (2) introducing into the first plurality of mammalian cells a nucleic acid, each of the nucleic acid comprising: (i) a second recombination site recognized by the serine integrase, (ii) a polynucleotide encoding a variant of the target gene, wherein at least one of the nucleic acids comprises a desired variant of the target gene, thereby generating a second plurality of mammalian cells comprising the nucleic acids; (3) expressing in each of the second plurality of mammalian cells the serine integrase, and (4) maintaining the second plurality of mammalian cells expressing the serine integrase under conditions that facilitate recombination between the first and the second recombination sites mediated by the serine integrase, thereby generating a cell comprising a third plurality of mammalian cells each of which comprises a variant of the target gene at the genomic locus; wherein each of the first plurality of mammalian cells further comprises at the genomic locus a first promoter capable of driving the expression of the variant of the target gene in the third plurality of mammalian cells; wherein the first promoter is a Tet-on promoter; wherein the first plurality of mammalian cells are HEK293 cells; wherein the target gene is an enzyme; wherein the target gene is a site-specific recombinase (see entire document including Figure 1A and 1B).
Sclimenti does not explicitly teach:
a) as in claims 1-4, 7-9 and 13-14, (2) introducing into mammalian cells a library of nucleic acid constructs; wherein the specific genomic locus is Hipp11 (H11) locus; wherein the serine integrase is Bxb1 integrase; wherein the Bxb1 integrase is expressed using a construct comprising polynucleotide sequence as set forth in SEQ ID NO: 1; wherein each of the nucleic acid constructs further comprises a selectable marker; wherein each of the first plurality of mammalian cells further comprises at the genomic locus a second promoter capable of driving the expression of the selectable marker in the third plurality of mammalian cells; wherein the second promoter is an EF-1 alpha promoter; wherein the site-specific recombinase is Bxb1 integrase; wherein the site-specific recombinase recognizes a variant recombination site.
With regards to claims 1-4, 7-9 and 13-14, Carlos teaches:
a) as in claims 1-4, 7-9 and 13-14, (2) introducing into mammalian cells a library of nucleic acid constructs; wherein the specific genomic locus is Hipp11 (H11) locus; wherein the serine integrase is Bxb1 integrase; wherein the Bxb1 integrase is expressed using a construct comprising polynucleotide sequence as set forth in SEQ ID NO: 1; wherein each of the nucleic acid constructs further comprises a selectable marker; wherein each of the first plurality of mammalian cells further comprises at the genomic locus a second promoter capable of driving the expression of the selectable marker in the third plurality of mammalian cells; wherein the second promoter is an EF-1 alpha promoter; wherein the site-specific recombinase is Bxb1 integrase; wherein the site-specific recombinase recognizes a variant recombination site (see Figure 1 and [0055] to [0092]).
One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have had a reasonable expectation of success in arriving at the Applicant's invention as claimed with the above cited references before them. One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have recognized functional equivalents in the substitution of Carlos's serine integrase Bxb1 for Sclimenti's serine integrase phiC31, especially in view of the similar nature of both teachings with respect to serine integrases, and in view of the detailed use of both Bxb1 and phiC31 provided by Carlos (see Figure 1 and [0055] to [0092]).
Sclimenti does not explicitly teach:
a) as in claims 1 and 15-20, a method of generating a cell library for screening a desired variant of a target gene, the method comprising: (2) introducing into cells a library of nucleic acid constructs; wherein the target gene is a Cas protein; wherein the Cas protein is Cas9; wherein the variant of the Cas protein recognizes a variant protospacer adjacent motif (PAM); wherein the target gene is a virus capsid gene; wherein the virus capsid gene is a lentivirus capsid gene; wherein the variant of the virus capsid gene has increased packaging ability of packaging>10 kb DNA in size or increased infectivity to a target cell/tissue.
With regards to claims 1 and 15-20, Payne teaches:
a) as in claims 1 and 15-20, a method of generating a cell library for screening a desired variant of a target gene, the method comprising: (2) introducing into cells a library of nucleic acid constructs; wherein the target gene is a Cas protein; wherein the Cas protein is Cas9; wherein the variant of the Cas protein recognizes a variant protospacer adjacent motif (PAM); wherein the target gene is a virus capsid gene; wherein the virus capsid gene is a lentivirus capsid gene; wherein the variant of the virus capsid gene has increased packaging ability of packaging>10 kb DNA in size or increased infectivity to a target cell/tissue (see [0012] to [0051]).
One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have had a reasonable expectation of success in arriving at the Applicant's invention as claimed with the above cited references before them. One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have recognized the advantages of substituting Payne's library for Carlos's and Sclimenti's individual construct in order to screen multiple targets at one time in a library. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the time of the effective filing date of the claimed invention.
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.
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Claims 1-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of U.S. Patent Number 11492613.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of generating a cell library for screening a desired variant of a target gene, the method comprising: (1) obtaining a first plurality of mammalian cells each of which comprises at a genomic locus a first recombination site recognized by a serine integrase, and (2) introducing into the first plurality of mammalian cells a library of nucleic acid constructs, each of the nucleic acid constructs comprising: (i) a second recombination site recognized by the serine integrase, (ii) a polynucleotide encoding a variant of the target gene, wherein at least one of the nucleic acid constructs comprises a desired variant of the target gene, thereby generating a second plurality of mammalian cells comprising the library of nucleic acid constructs; (3) expressing in each of the second plurality of mammalian cells the serine integrase, and (4) maintaining the second plurality of mammalian cells expressing the serine integrase under conditions that facilitate recombination between the first and the second recombination sites mediated by the serine integrase, thereby generating a cell library comprising a third plurality of mammalian cells each of which comprises a variant of the target gene at the genomic locus and claim 1 in U.S. Patent Number 11492613 is drawn to a method of screening for a desired variant of a target site-specific recombinase, the method comprising: (1) obtaining a first plurality of mammalian cells each of which comprises at a genomic locus (i) a first recombination site recognized by a serine integrase, wherein the serine integrase is different from the target site-specific recombinase and (ii) a first promoter and a second promoter; (2) generating a cell library by (i) introducing into the first plurality of mammalian cells a library of nucleic acid constructs, each of the nucleic acid constructs comprising: (a) a second recombination site recognized by the serine integrase (b) a polynucleotide encoding a variant of the target site-specific recombinase, and (c) a first selectable marker, thereby generating a second plurality of mammalian cells comprising the library of nucleic acid constructs, wherein at least one of the nucleic acid constructs comprises a polynucleotide encoding the desired variant of the target site-specific recombinase, (ii) expressing in each of the second plurality of mammalian cells the serine integrase, and (iii) maintaining the second plurality of mammalian cells expressing the serine integrase under conditions that facilitate recombination between the first and the second recombination sites mediated by the serine integrase, thereby generating a cell library comprising a third plurality of mammalian cells each of which comprises a variant of the target site-specific recombinase at the genomic locus, wherein the first promoter drives the expression of the variant of the target site-specific recombinase and the second promoter drives the expression of the first selectable marker; (3) selecting, from the cell library, a mammalian cell expressing the desired variant of the target site-specific recombinase by (i) introducing a selection construct to each mammalian cell of the cell library, wherein the selection construct comprises (a) a third recombination site, (b) a fourth recombination site, and (c) a second selectable marker, wherein at least one of the third and the fourth recombination sites are not recombined by the target site-specific recombinase but are recombined by the desired variant of the target site-specific recombinase, and wherein the second selectable marker is not expressed in the absence of a recombination between the third and the fourth recombination sites in the mammalian cell, and (ii) maintaining the cell library with the selection construct under conditions that facilitate recombination between the third and the fourth recombination sites mediated by the desired variant of the target site-specific recombinase, and (iii) detecting expression or the lack of expression of the second selectable marker that indicates the recombination between the third and the fourth recombination sites in the mammalian cell, and (4) generating from the mammalian cell selected in step (3) a polynucleotide encoding the desired variant of the target site-specific recombinase.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 11492613.
Claims 1-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-13 of U.S. Patent Number 12291706.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of generating a cell library for screening a desired variant of a target gene, the method comprising: (1) obtaining a first plurality of mammalian cells each of which comprises at a genomic locus a first recombination site recognized by a serine integrase, and (2) introducing into the first plurality of mammalian cells a library of nucleic acid constructs, each of the nucleic acid constructs comprising: (i) a second recombination site recognized by the serine integrase, (ii) a polynucleotide encoding a variant of the target gene, wherein at least one of the nucleic acid constructs comprises a desired variant of the target gene, thereby generating a second plurality of mammalian cells comprising the library of nucleic acid constructs; (3) expressing in each of the second plurality of mammalian cells the serine integrase, and (4) maintaining the second plurality of mammalian cells expressing the serine integrase under conditions that facilitate recombination between the first and the second recombination sites mediated by the serine integrase, thereby generating a cell library comprising a third plurality of mammalian cells each of which comprises a variant of the target gene at the genomic locus and claim 1 in U.S. Patent Number 12291706 is drawn to a method of generating a mammalian cell library for screening a desired variant of a target gene, the method comprising: (1) obtaining a first plurality of mammalian cells each of which comprises at genomic locus Hipp11 (H11) an attP site recognized by a Bxb1 integrase; (2) introducing into the first plurality of mammalian cells a library of nucleic acid constructs wherein at least one of the nucleic acid constructs comprises the desired variant of the target gene, each of the nucleic acid constructs comprising: a) an attB site recognized by the Bxb1 integrase, and b) a variant of a target gene, thereby generating a second plurality of mammalian cells comprising the library of nucleic acid constructs, wherein at least one of the second plurality of mammalian cells comprises the desired variant of the target gene: (3) expressing in each of the second plurality of mammalian cells the Bxb1 integrase encoded by the polynucleotide sequence of SEQ ID NO: 1 wherein the Bxb1 coding sequence is operably linked to an expression control sequence; and (4) maintaining the second plurality of mammalian cells under conditions that facilitate recombination between the attP and the attB sites mediated by the Bxb1 integrase to integrate the variants of the target gene at the genomic locus H11, thereby generating the mammalian cell library comprising a third plurality of mammalian cells each of which comprises a variant of the target gene at the genomic locus H11 wherein integration of the variants of the target gene at the genomic locus H11 does not involve a unidirectional recombinase other than the Bxb1 integrase.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 12291706.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Christian Boesen whose telephone number is 571-270-1321. The Examiner can normally be reached on Monday-Friday 9:00 AM to 5:00 PM.
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/CHRISTIAN C BOESEN/Primary Examiner, Art Unit 1684