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
Applicant’s election without traverse of group I, variant gene of interest, ii) expression level of recombinant protein of interest by said cell, protein fused to fluorescent protein or a fluorescent protein a protein; a protein in the reply filed on 12/18/2025 is acknowledged.
Claims 19-22 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/18/2025.
Priority
The instant application was filed 10/04/2022 and is a national stage entry of PCT/EP2021/058918 with an international filing date: 04/06/2021 and claims foreign priority to GB2005179.3, filed 04/08/2020.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) submitted on 10/4/2022, and 11/3/2025 are being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 1-18 objected to because of the following informalities:
Clam 1 recites, “a.”, “b.”. “c.”, “a.”, “b.” “c.”, “d.” MPEP 608.01(m) states: Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v.Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Clam 2 recites, “e.” MPEP 608.01(m) states: Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v.Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite because it lacks a positive active step relating back to the preamble. The preamble recites a method for the selection of a sequence optimized nucleic acid sequence from a plurality of nucleic acid sequence variants, however the last positive active step is drawn to selecting and isolating a cell with a defined phenotype from the cells. Therefore it is unclear as to whether the method is drawn to method for the selection of a sequence optimized nucleic acid sequence from a plurality of nucleic acid sequence variants or selecting and isolating a cell with a defined phenotype from the cells.
Claim 1 recites, “optimized nucleic acid sequence.” The recitation of optimized nucleic acid sequence suggests there are non-optimized nucleic acid sequence. The specification and claims do not provide a standard or definition to differentiate optimized nucleic acid sequence from non-optimized nucleic acid sequence. Thus the metes and bounds are unclear.
Claim 1 recites,” said sequence optimized nucleic acid sequence corresponding to said defined phenotype.” The specification teaches, “a "defined phenotype" meaning that for analysis and selection purposes of said optimized sequence variant, a cell having a particular physical characteristic or behavior as previously defined and discussed herein will be selected.” The teachings of the specification are limited to an optimized nucleic acid sequence which is indefinite for the reasons of record. Thus the metes and bounds are unclear.
Claim 1 recite, “nucleic acid sequence variant.” The recitation of variant suggests there is non-variant. Review and searching of the specification did not reveal a standard to differentiate a variant from non-variant. Thus the metes and bounds are unclear.
Claim 2 recite, “wherein each of the plurality of donor vectors of step ii) further comprises: e. an expression cassette encoding a second selection marker; and wherein said method further comprises the steps of: vi) excising a nucleic acid sequence flanked by the nucleic acid sequences El and E2 from a cell of step iii) or selected and isolated in step iv) or step v) in the presence of a second DNA enzyme, wherein the presence of the second DNA enzyme enables recombination between the nucleic acid sequences El and E2, wherein the presence of an expression cassette encoding a second selection marker that is not flanked by the nucleic acid sequences El and E2 in a cell is indicative of a stable integration of a donor vector at a genomic location outside the pre-defined genomic location of said cell; and vii) selecting cleavage. Thus the metes and bounds are unclear how to select a cell if isolation of nucleic acids prior to excision destroys the cell.
Regarding claim 6 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 8 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 13 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 14 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 16 recites, “plurality of donor vectors comprises nucleic acid sequence variants encoding essentially identical amino acid sequence variants of said recombinant protein of interest.” The recitation of essentially identical amino acid sequence variants suggests there are not essentially identical amino acid sequence variants. The claims and specification do not provide a standard or definition to differentiate essentially identical amino acid sequence variants from not essentially identical amino acid sequence variants
Regarding claim 17 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 17 recites, “a nucleic acid sequence region comprising essentially identical nucleic acid sequences to encode essentially identical recombinant proteins of interest but wherein said nucleic acid sequence region comprises different nucleic acid sequence variants of donor vector components.” The recitation of essentially identical nucleic acid sequences to encode essentially identical recombinant proteins of interest suggests there are not essentially identical nucleic acid sequences to encode not essentially identical recombinant proteins of interest. The claims and specification do not provide a standard or definition to differentiate essentially identical amino acid sequence variants from not essentially identical amino acid sequence variants
Claim 18 recites, “wherein said method identifies sequence optimized nucleic acid donor vector components for use in recombinant protein expression systems based on a eukaryotic cell system” The recitation of optimized nucleic acid donor vector components suggests non-optimized nucleic acid donor vector components. The specification and claims do not appear to provide a definition or standard on how to differentiate optimized nucleic acid donor vector components from non-optimized nucleic acid donor vector components. Further claim 18 is vague and unclear as to provides the intended outcome of the independent claim, but does not provide any specific limitations which provide for the outcome.
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.
Claim(s) 1-5, 8, 15-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nandy (PLANT BIOTECHNOLOGY JOURNAL, vol. 10, no. 8, 12 June 2012 (2012-06-12), pages 904-912), AYDIN (MOLECULAR BIOTECHNOLOGY ; PART B OF APPLIED BIOCHEMISTRY AND Biotechnology (2011-01-28), pages 82-89), and Wang (Plant Cell Rep (2011) 30:267–28).
This rejection is set forth in part due to the numerous 112 issues as the claims can best be understood. It is noted the claims are broad as the claims recite, E1, I1, E2, I2, promoter, defined phenotype first DNA enzyme, second DNA enzyme, donor vector, etc. These limitations generally provide names to what can be encompassed, but do not provide for any specific limitations.
Nandy teaches, “Site-specific recombination (SSR) systems carryout recombination between specific DNA sequences without addition or deletion of nucleotides (Van Duyne, 2001). This precision is highly desirable in plant genetic engineering as it. minimizes unintended mutations introduced by the transformation process. Most SSR systems are fairly simple involving a single recombinase protein that catalysis recombination between short DNA sequences (Hirano et al., 2011). in addition, these systems are functional in a variety of plant species, making them attractive tools for genetic engineering (Darbani et al., 2007; Gidoni et al., 2008; Ow, 2011; Srivastava and Gidoni, 2010). Although several SSR systems are under development, some efficient systems are already available such as P1 phage Cre-lox and yeast FLP-FRT systems. These systems have been widely used for (a) removing antibiotic selection marker genes from transgene locus (marker excision) and (b) integrating transgene into the predetermined genomic site (site-specific integration or SSI) (Gidoni et al., 2008; Srivastava and Gidoni, 2010; Tuteja et al., 2012). While marker excision technology is widely practiced, SSR-mediated gene integration technology IS not being utilized in spite of its distinct ability to generate precise SSI locus and consistent transgene expression (Akbudak et al., 2010; Albert et al., 1995; Chawla et al., 2006; Day et al., 2000; Nanto et al., 2009; Srivastava et al., 2004; Vergunst et al., 1998). One of the reasons for its inapplicability so far is the difficulty in removing marker genes from the SSI locus and recovering marker-free SSI (MF-SSI) lines (Ow, 2002). Marker excision combined with site-specific gene integration requires the use of two SSR systems (Darbani et al., 2007; Fladung and Becker, 2010; Nanto and Ebinuma, 2008; Srivastava and Ow, 2004), and for a long time, only Cre-/ox system was popularly used (Gilbertson, 2003). Recent studies have validated additional SSR systems for plant biotechnology, opening the doors for MF-SSI technology (Fladung et al., 2010; Moon et al., 2011; Nandy and Srivastava, 2011; Nanto et al., 2005; Thomson et al., 2009, 2010, 2012; Zhou et al., 2012). The feasibility of MF-SSI has been demonstrated in two previous studies (Akbudak and Srivastava, 2011; Nanto and Ebinuma, 2008). Nanto and Ebinuma (2008) used a combination of R-RS and Cre-/ox for transgene integration and marker excision, respectively, for generating MF-SSI plants of tobacco. Using rice callus cultures, Akbudak and Srivastava (2011) showed that SSI locus developed by Cre-lox system can be efficiently converted to MF-SSI locus by employing FLP-FRT system for marker excision. The critical component of this study was the use of thermostable FLP recombinase, FLPe, rather than the wild-type FLP. In both studies, however, the excision recombinase (Cre or FLPe) was introduced by retransformation of SSI lines, which relies on the use of selectable marker genes, thus adding extra steps for removing this newly added marker gene. Marker excisions can also be initiated by manual crosses; how- ever, that would also entail a time-consuming multi-generation screening for developing the final product.” (introduction)
Aydin teaches, “Selectable marker genes encoding resistance to antibiotics and herbicides are co-transformed with the gene-of-interest (GOI) during plant transformation to facilitate isolation of transformed clones. Otherwise, large-scale screening based on polymerase chain reaction (PCR) is implemented to isolate transformed clones, which is an inefficient and expensive approach [1]. Presence of marker genes such as antibiotic resistance and herbicide resistance genes in transgenic crops, however, is considered a major environ- mental and health risk [2]. To address these concerns, an alternative marker gene encoding phospho-mannose isomerase (PMI) has been developed that allows isolation of clones on mannose supplemented media [3]. However, superfluous expression of marker genes in transgenic plants cannot be prevented unless they are removed. If the marker gene and the GOI integrate into genetically segregated loci, GOI-containing "marker-free" transgenic plants can be recovered in the next generation. However, in the majority of transgenic events and in precise transformation strategies the marker gene is linked to the GOI; therefore, its removal relies on DNA excision technologies. One of the popular approaches for excising marker genes is based on the use of Cre-lox site-specific recombination (SSR) system, which can excise a specific DNA fragment if flanked by loxP sequences. Alternative SSR systems are also available; however, their efficiency was found to be significantly lower [4-10]. Cre-lox system has also been used for site-specific transgene integration to generate precise full-length integration of transgenes in a pre-determined chromosomal location [11-13]. The site-specific integration approaches also utilize selection marker genes, excision of which relies on the use of a second SSR system. For example, SSI locus developed by Cre-lox system should be subjected to marker excision by a second SSR system such as FLP-FRT [14, 15]. In the present study, the feasibility of converting an SSI locus into marker-free locus was tested by using Cre-lox and FLP-FRT systems. An SSI locus containing FRT-flanked marker gene, neomycin phospho- transferase II (NPT), was generated by Cre-lox mediated transgene integration, which was subjected to NPT excision upon the introduction of FLP activity by re-transformation. First, a heat-inducible or a constitutively expressed FLP gene was employed. This FLP gene, referred to as wild- type FLP (FLPwt) in the present study, is a modified version of the native yeast FLP gene. The FLPwt carries silent mutations to remove three canonical polyadenylation AATAAA signals and cryptic splice acceptor sites [16]. FLP activity encoded by FLPwt gene has been shown to be functional in a variety of plant cells and effective in marker removal [8, 9, 17-19]. However, FLPwt activity in the present work failed to excise marker gene from the rice genome. Instead, the use of an enhanced FLP (FLPe), a thermostable version of wild-type FLP (FLPwt), generated ~ 100% excision in 5 out of 10 transgenic lines containing the SSI locus. Thus, FLPe-FRT-mediated marker excision is highly efficient in rice and suitable for generating marker-free site-specific integration lines.” (introduction)
Wang provides a review of recombinase technology and applications. Wang teaches, “We also provide alternative strategies for the combined use of multiple site-specific recombinase systems for genome engineering to precisely insert transgenes into a pre-determined locus, and removal of unwanted selectable marker genes. “ Abstract) Wang teaches recombinase superfamily and integration of genes of interest relative to promoters and use of markers. (figures, throughout). Wang discusses the use of promoters in recombination events( p 270) Wang teaches use of recombinase to introduce a gene of interest (GOI) or protein (figures). Wang teaches, “. As can be seen, recombinase-mediated excision offers many benefits over traditional genomic engineering methods, namely the removal of unwanted DNA, recycling of selectable markers and resolution of complex transgene concatemers to single copy stable loci” (page 272, 1st column) Wang teaches the use of FACS to detect and sort cells based on gene expression (page 279, 1st column).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to contact a population of eukaryotic cells containing recombinase site with a donor vector providing compatible recombination sites a selection marker and nucleic acid sequence variant, and selecting cells based on a selection marker such as antibiotic resistance and/or cell morphology or gene expression by FACS. The artisan would have a reasonable expectation of success as the artisan is merely using known methods.
With regards to claim 2, Wang teaches, “We also provide alternative strategies for the combined use of multiple site-specific recombinase systems for genome engineering to precisely insert transgenes into a pre-determined locus, and removal of unwanted selectable marker genes.” (abstract)
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Thus it would have been further prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claim to excise one nucleic acid sequence or marker and introduce a second maker or gene by use of a second recombinase. The artisan would be motivated as Wang appears to specifically suggest the use of multiple recombination steps using different recombinases and target sequences. The artisan would have a reasonable expectation of success as the artisan is merely using known methods of use recombinases to introduces multiple markers or genes of interest into cells.
With regards to claim 3, Wang teaches sequence analysis.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to sequence the nucleic acids or variants that are introduced into the cells. The artisan would be motivated to sue sequencing to allow for analysis of the nucleotide sequence and detect variants. The artisan would have a reasonable expectation of success as the artisan is merely using known methods to analyze nucleic acid sequence.
With regards to claims 4, Wang, Nandy, and Aydin teach genes of interests and variants.
With regards to claim 5, 8 16-18Wang teaches use of FACS to sort cells. Thus detection of recombinant protein expression.
With regards to claim 14, Wang teaches FACS or flow cytometry.
Claim(s) 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nandy (PLANT BIOTECHNOLOGY JOURNAL, vol. 10, no. 8, 12 June 2012 (2012-06-12), pages 904-912), AYDIN (MOLECULAR BIOTECHNOLOGY ; PART B OF APPLIED BIOCHEMISTRY AND Biotechnology (2011-01-28), pages 82-89), and Wang (Plant Cell Rep (2011) 30:267–28) as applied to claim1-5, 8, 15-18 above, and further in view of Tang (Cell 154, 928–939, August 15, 2013)
The teachings of Nandy, Aydin and Wang are drawn to use of recombinases to insert genes of interest or markers into cells. Nandy, Aydin and Wang do not specifically teach the use of antibodies or nanobodies and/or fluorescent proteins.
However Tang teaches nanobody-based system using fluorescent proteins. Tang teaches, “We explored whether artificially derived binding proteins can confer GFP with the ability to regulate genes. GFP seems relatively inert in many heterologous systems; it is freely diffusible in the cytoplasm, can enter the nucleus, confers low cytotoxicity, and has few interactions with host proteins (Trinkle Mulcahy et al., 2008). The development of GFP-binding proteins (GBPs) from Camelid antibodies (Kirchhofer et al., 2010) has made possible the construction of GBP-fusion proteins non covalently linking GFP to a variety of proteins in living cells (Caussinus et al., 2012). These reagents, termed nanobodies, are single-chain antigen-binding domains that are relatively small in size ( 300–400 bp) and can be easily expressed in living cells (Rothbauer et al., 2006). Given the availability of multiple GBPs, we reasoned that GFP might be used as a scaffold to organize the formation of biologically active complexes. In one scheme, GFP would act like a small-molecule ‘‘dimerizer,’’ bridging the association of distinct modular domains or protein fragments to reconstitute useful activities such as transcription and recombination (Jullien et al., 2003; Pollock and Clackson, 2002).”
Therefore it would have prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use GFP labeled proteins, antibodies or nanobodies as the gene, protein or marker of interest. The artisan would have been motivated to use GFP labeled proteins, antibodies or nanobodies as the gene, protein or marker of interest in cells using recombination as taught by Nandy, Aydin and Wang to produce GFP labeled proteins, antibodies or nanobodies. The artisan would have a reasonable expectation of success as the artisan is merely using known proteins with known sequence to produce quantities of GFP labeled proteins, antibodies or nanobodies.
With regards to claim 6, 9, 11-12 antibodies have a membrane anchor and is expressed on cell surface and has affinity..
With regards to claim 10, Wang teaches nanobodies.
Claim(s) 15-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nandy (PLANT BIOTECHNOLOGY JOURNAL, vol. 10, no. 8, 12 June 2012 (2012-06-12), pages 904-912), AYDIN (MOLECULAR BIOTECHNOLOGY ; PART B OF APPLIED BIOCHEMISTRY AND Biotechnology (2011-01-28), pages 82-89), and Wang (Plant Cell Rep (2011) 30:267–28) as applied to claim1-5, 8, 15-18 above, and further in view of Mauro (Methods Mol Biol . 2018:1850:275-288.)
This rejection is drawn to the interpretation optimized sequence requires codon optimization.
The teachings of Nandy, Aydin and Wang are drawn to use of recombinases to insert genes of interest or markers into cells. Nandy, Aydin and Wang do not specifically teach codon optimization.
However, Mauro teaches, “Codon optimization refers to approaches using synonymous mutations to increase protein expression from a gene of interest. This approach is routinely used to enhance recombinant protein expression, both for bioproduction applications, as well as for in vivo nucleic acid therapeutic applications [18, 19]. This approach is often used simply to increase expression, particularly when a protein is expressed in a heterologous expression system, to match the expression system [20, 21].”
Therefore it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims to provide multiple different nucleotide sequences encoding the same amino acid sequence or essentially the same nucleotide sequence. The artisan would be motivated to use multiple different nucleotide sequences encoding the same amino acid sequence or essentially the same nucleotide sequence to identify which nucleotide sequence provides for the highest or best protein expression. Thea artisan would have a reasonable expectation of success as the artisan is merely using known methods to maximize protein production.
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.
Claims 1-18 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-36 of copending Application No. 17/995,571. Although the claims at issue are not identical, they are not patentably distinct from each other because coextensive in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is drawn to A method for the selection of a sequence optimized nucleic acid sequence from a plurality of nucleic acid sequence variants, wherein said sequence optimized nucleic acid sequence corresponds to a eukaryotic cell with a defined phenotype, said method comprising: i) providing a population of isolated eukaryotic cells, each cell comprising a pre- defined genomic location, which pre-defined genomic location comprises: a. a nucleic acid sequence Il comprising a recognition site for a first DNA enzyme’s. a nucleic acid sequence El comprising a recognition site for a second DNA enzyme; and c. a promotor nucleic acid sequence; ii) providing a plurality of donor vectors, each donor vector comprising: a. a nucleic acid sequence 12;b. a nucleic acid sequence E2 comprising a recognition site for said second DNA enzyme; c. a nucleic acid sequence encoding a first selection marker; and. a nucleic acid sequence region comprising a nucleic acid sequence variant, iii) contacting the plurality of donor vectors with the population of cells in the presence of a first DNA enzyme, wherein the presence of the first DNA enzyme enables recombination between the nucleic acid sequence 12 of a donor vector and the nucleic acid sequence Il present in the pre-defined genomic location of a cell; iv) selecting and isolating a cell having a donor vector integrated at the pre-defined genomic location by detecting the expression of the first selection marker in the cell, wherein the expression of the first selection marker is activated by the promotor nucleic acid sequence at the pre-defined genomic location; and v) selecting and isolating a cell with a defined phenotype from the cells of step iv), thereby selecting and isolating a sequence optimized nucleic acid sequence from said nucleic acid sequence variants, said sequence optimized nucleic acid sequence corresponding to said defined phenotype.
The claims of 571 are drawn to A method for targeted integration of a donor vector into a pre-defined genomic location of an isolated eukaryotic cell, said method comprising: I) Providing an isolated eukaryotic cell comprising a pre-defined genomic location, which pre-defined location comprises: a. a nucleic acid sequence Il comprising a recognition site for a first DNA enzyme; b. a nucleic acid sequence El comprising a recognition site for a second DNA enzyme; and c. a promotor nucleic acid i) providing a donor vector comprising: a. a nucleic acid sequence 12; b. a nucleic acid sequence of interest; c. a nucleic acid sequence E2 comprising a recognition site for said second DNA enzyme; d. a nucleic acid sequence encoding a first selection marker; e. optionally an expression cassette encoding a second selection marker; iii) contacting the donor vector with the cell in the presence of a first DNA enzyme, wherein the presence of the first DNA enzyme enables recombination between the nucleic acid sequence 12 of the donor vector and the nucleic acid sequence Il present in the pre-defined genomic location of the cell; iv) Selecting a cell having the donor vector integrated at the pre-defined genomic location by detecting the expression of the first selection marker in the cell, wherein the expression of the first selection marker is activated by the promotor nucleic acid sequence P1 at the pre-defined genomic location; and v) isolating the cell.
Thus it is prima facie obvious to one of skill in the art prior to the effective filing dare of the claims the claims of 571 are obvious as they encompass the instant claims.
Dependent claim are obvious as they are coextensive in scope.
Claims 1-18 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,802, 297. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
Claim 1 is drawn to A method for the selection of a sequence optimized nucleic acid sequence from a plurality of nucleic acid sequence variants, wherein said sequence optimized nucleic acid sequence corresponds to a eukaryotic cell with a defined phenotype, said method comprising: i) providing a population of isolated eukaryotic cells, each cell comprising a pre- defined genomic location, which pre-defined genomic location comprises: a. a nucleic acid sequence Il comprising a recognition site for a first DNA enzyme’s. a nucleic acid sequence El comprising a recognition site for a second DNA enzyme; and c. a promotor nucleic acid sequence; ii) providing a plurality of donor vectors, each donor vector comprising: a. a nucleic acid sequence 12;b. a nucleic acid sequence E2 comprising a recognition site for said second DNA enzyme; c. a nucleic acid sequence encoding a first selection marker; and. a nucleic acid sequence region comprising a nucleic acid sequence variant, iii) contacting the plurality of donor vectors with the population of cells in the presence of a first DNA enzyme, wherein the presence of the first DNA enzyme enables recombination between the nucleic acid sequence 12 of a donor vector and the nucleic acid sequence Il present in the pre-defined genomic location of a cell; iv) selecting and isolating a cell having a donor vector integrated at the pre-defined genomic location by detecting the expression of the first selection marker in the cell, wherein the expression of the first selection marker is activated by the promotor nucleic acid sequence at the pre-defined genomic location; and v) selecting and isolating a cell with a defined phenotype from the cells of step iv), thereby selecting and isolating a sequence optimized nucleic acid sequence from said nucleic acid sequence variants, said sequence optimized nucleic acid sequence corresponding to said defined phenotype.
The claims of 297 are drawn to A method to obtain a cell suitable for expressing a protein of interest comprising the following steps: a) integration of a nucleic acid molecule comprising a polynucleotide encoding a first protein of interest into a pre-defined site in the genome of a recipient cell, wherein the nucleic acid molecule comprises in 5′ to 3′ sequence order: a first recombinase recognition sequence; a first copy of a second recombinase recognition sequence; a promoter-less selection marker gene and the polynucleotide encoding the first protein of interest, wherein the promoter-less selection marker and the polynucleotide encoding the first protein of interest are in any order and orientation; and an additional copy of said second recombinase recognition sequence, wherein the first and the second recombinase recognition sequences are recognition sequences for different recombinases; b) identification of cells expressing the first protein of interest; c) excision of the nucleic acid molecule comprising a polynucleotide encoding the first protein of interest from the genome of the identified cells to provide a resulting cell containing the first recombinase recognition sequence and a copy of the second recombinase recognition sequence enabling targeted introduction of a nucleic acid molecule encoding a second protein of interest into said pre-defined site in the genome; and d) subsequent to step c), integration of the nucleic acid molecule encoding the second protein of interest into the pre-defined site in the genome of the resulting cell.
Thus it is prima facie obvious to one of skill in the art prior to the effective filing dare of the claims the claims of 297 are obvious as they encompass the instant claims.
Dependent claim are obvious as they are coextensive in scope.
Summary
No claims are allowed.
Conclusion
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
