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 .
Application Status
The preliminary amendment filed December 1, 2022 is acknowledged. Claims 1-8, 10-18, 45, 50, 63 and 69-70 are pending and under examination.
Drawings
The drawings are objected to because the lines, shadings, numbers and letters of FIGs 1-5, 11, 17, 21, 23, 25, 27 and 40 are not sufficient to provide satisfactory reproduction characteristics. 37 CFR 1.84(l) states that “all drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.” In the instant case, the text in the noted FIGs is light grey, very small, of poor resolution, or otherwise not sufficiently dense and dark to permit satisfactory reproduction characteristics; and the letters over shading especially in FIGs with vector maps are not sufficiently dark for reproduction.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the terms EX-CELL® CD, ClonaCellTM-CHO, ActiProTM, CHOZN®, and SYPRO®, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(b)
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 5-7 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 5 recites “wherein the nucleic acid construct comprises an extending packaging region between the first promoter and the selectable marker”. Claim 5 is indefinite because it is not clear what an “extending packaging region” (EPR) is or what the minimum sequence requirements of the EPR are. The Specification recites an “extended packing region” and an “extending packaging region” two times, on page 3 and on page 9. Page 3 states “In some preferred embodiments, the nucleic acid construct comprises an extending packaging region (EPR) between the first promoter and the selectable marker. In some preferred embodiments, the EPR comprises multiple potential Kozak sequences and/or ATG translation start sites.” Page 10 refers to an EPR = MMLV Extended Packaging Region. Page 41 also recites “without being limited to any particular mechanism, the known presence of a weak Kozak sequence in the EPR could lead to aberrant translation, reducing the translation efficiency of the GS protein.” The only reference to an MMLV Extended Packaging Region in the are, was from a plasmid vector manual from Agilent (pVPack Vectors, 217566-12, published 2015; page 6), which describes “an extended version of the viral packaging signal, psi-plus). However, the manual states that the packaging signal is required for viral RNA to be packaged into virion particles (page 6, ¶1). It is not clear how a Kozak sequence and ATG sequences, which play a role in protein translation is related to a signal for packaging viral RNAs in the viral capsids. As such, it is not clear what the sequence or minimum components of the EPR are.
Claim 6 is rejected for depending from claim 5 and not remedying the indefiniteness. Although claim 6 recites having a Kozak sequence and/or ATG translation start site, it is not clear how those relate to viral RNA packaging signals or if there are a separate element. As such it is not clear what sequences are required.
Claim 7 recites “wherein the first promoter sequence is a weak promoter sequence”. The term “weak” is a relative term which renders the claim indefinite. The term “weak” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Although the Specification provides examples of weak promoters, including the MMSV 5’ proviral SIN-LTR (page 10), weaker than a generic SIN LTR promoter or the UBC promoter (page 29). However, the cited passages are not definitions and the Specification does not define transcriptional cutoffs or specific cells for what constitutes week expression. As such, the claim is indefinite.
Claim Interpretations
The claims recite “a selectable maker”. The Specification defines “selectable marker” as a gene that encodes an enzymatic activity or other protein that confers the ability to grow in medium lacking what would otherwise be an essential nutrient; in addition, a selectable marker may confer resistance to an antibiotic or drug upon the cell in which the selectable marker is expressed.) (page 15, ¶2). This disclosure is interpreted as limiting the genus of “selectable markers” to those that can limit or permit growth under specific conditions. Although fluorescent and bioluminescent proteins like Luciferase and GFP are known in the art to allow selection by visual means, they do not affect growth in medium lacking essential nutrients or having antibiotic/drugs. As such the nucleic acid sequences encoding fluorescent and bioluminescent proteins are not encompassed by the claimed “selectable marker sequence”.
The claims also recite elements in “operable association” which is described in the specification as “linkage of nucleic acid sequence in such a manner that a nucleic acid molecule capable of directing the transcription of a given gene and/or the synthesis of a desired protein molecule is produced.” (page 15, ¶1). In the art, promoter sequences and polyA sequences drive and stop, respectively, the expression of a sequence that codes for a protein or noncoding. Promoters are not known to act on other promoters. As such “in operable association” is interpreted as applying to the first promoter sequence and selectable marker sequence as an expression unit, and as applying to the second promoter sequence the nucleic acid sequence encoding the protein of interest and the polyA signal.
Claim Rejections - 35 USC § 102 - Zaiss
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 8, 14, 17, 45-50 and 69-70 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zaiss (Zaiss et al., Journal of Virology (2002), 76: 7209-7219).
Regarding claim 1, Zaiss teaches a nucleic acid construct comprising from 5’ to 3’ 1) an EF1a E/P (i.e., a first promoter) operable linked to 2) a tk coding sequence (i.e., thymidine kinase, a selectable marker), 3) a PGK promoter (i.e., a second promoter sequence) operably linked to 4) neo (i.e., a first protein of interest), and 5) bGHpA (i.e., a polyA signal sequence) (Fig 6A). Zaiss teaches the nucleic acid construct also comprises two loxP sites (i.e., insertion elements) that are between the first promoter and the poly A sequence (Fig 6A).
Regarding claim 2, Zaiss’s nucleic acid construct does not comprise a poly A sequence between the tk selectable marker and the PGKp promoter (Fig 6A).
Regarding claim 3, Zaiss teaches the tk coding sequence (i.e., the selectable marker) is adjacent to PGKp (i.e., the second promoter) (Fig 6A).
Regarding claims 4, Zaiss teaches PGKp (i.e., the second promoter) is adjacent to neo (i.e., the nucleic acid encoding the protein of interest).
Regarding claim 8, Zaiss teaches the tk gene is driven by the human EF1a promoter (Fig 6; page 7217, ¶3).
Regarding claims 14 and 17, Zaiss teaches the LoxP sites are recognized by the Cre recombinase (i.e., the LoxP insertions are a recombinase insertion element that is also an attachment site for the Cre recombinase) (Fig 6A).
Regarding claims 45 and 50, Zaiss teaches TE26 cells comprising the nucleic acid (i.e., 1 copy) described above for claim 1 (Fig 6A; page 7210, ¶5).
Regarding claims 69-70, Zaiss teaches the TE26 cells comprising the nucleic acid of claim 1 and also comprising an expression cassette for the Cre recombinase (i.e., a second nucleic acid construct encoding an enzyme that is a recombinase) (Fig 6A-B).
Claim Rejections - 35 USC § 102 - Bennett
Claims 1-2, 4-7, 12, 14, 17 and 45-50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bennett (US 20040219516 A1, published November 4, 2004). Claim 6 is evidenced by SnapGene (pLenti6 UbC V5-DEST, https://www.snapgene.com/plasmids/gateway_cloning_vectors/pLenti6_UbC_V5-DEST, retrieved January 21, 2026).
Regarding claim 1, Bennett teaches the features of the pLETI6/UbC/V5-DEST plasmid (i.e., a nucleic acid construct for expression of a protein of interest (FIG. 36D; [0873]). Bennett teaches the plasmid comprises 1) PUBC (i.e., a first promoter) operably linked to 2) CmR (i.e., the chloramphenicol resistance marker sequence), 3) PSV40 and the EM7 promoter (i.e., second promoter sequences), operably linked to 4) the blasticidin resistance gene (i.e., a nucleic acid sequence encoding a first protein of interest that is operably linked to the second promoter), and an SV40 polyadenylation signal sequence ([FIG. 36D; [0873]). Bennet also teaches the plasmid comprises attR sites (i.e., insertion elements) between the first promoter and the first resistance marker (FIG 36D, [0873]).
Regarding claim 2, Bennett teaches there is no polyA signal sequence between the CmR gene and the SV40 promoter (FIG. 36D, [0873]).
Regarding claim 4, Bennett teaches the EM7 promoter is adjacent to the Blasticidin gene (i.e., encoding the protein of interest).
Claim 5 is indefinite for the reasons described above in paragraphs 9 and 10. For the purpose of compact prosecution, claim 5 is interpreted as requiring a viral packaging sequence.
Regarding claim 5, Bennett teaches the plasmid also comprises an RSV promoter and an HIV-1 5’ LTR (i.e., a first promoter) (FIG. 36D, [0873]). Bennett teaches the plasmid also comprises an HIV-1 psi packaging signal and Rev response element between the 5’ LTR and the CmR selectable marker gene (i.e., an extending packaging sequence) (FIG. 36D; [0873]).
Claim 6 is indefinite for the reasons described above in paragraphs 9 and 10. For the purpose of compact prosecution, claim 6 is interpreted as requiring a viral packaging sequence and multiple ATG sequences between the first promoter and the selection marker.
Bennett teaches between downstream of the HIV-1 packaging sequence is ~ 1500 base pairs that also includes an RRE (Fig 36D). Bennet is silent as to the sequence of these 1500 base pairs. SnapGene teaches the features and sequences of pLentib Ubc V5-DEST. SnapGene teaches there are many ATG sequences between the HIV-1 packaging signal and the RRE.
Regarding claim 7, Bennet’s plasmid comprises the UBC promoter (FIG 36D, [0873]), which the Specification indicates is a weak promoter (page 29, ¶2).
Regarding claim 12, Bennett teaches the promoter driving expression of the blasticidin protein of interest is the SV40 promoter (FIG 36D, [0873]).
Regarding claims 14, Bennett teaches the insertion sites are attR site (i.e., recombinase insertion sites).
Regarding claims 45 and 50, Bennet teaches the pLenti6/UbC/V5-DEST plasmid for use in host cells to express one or more sequences (i.e., transduce 1 copy of the nucleic acid into host cells) ([0670]).
Claim Rejections - 35 USC § 103 - Shin
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4, 10-14, 17, 45, 50, 63 and 69-70 are rejected under 35 U.S.C. 103 as being unpatentable over Shen (US 20160115502 A1, published April 28, 2016).
Regarding claims 1 and 11-14, Shen teaches a plasmid (i.e., a nucleic acid) comprising from 5’ to 3’: a lox site (i.e., a recombinase insertion element), Hyg (i.e., a hygromycin selectable marker resistance gene), a CMV promoter (i.e., a second promoter) operably linked to a gene of interest that encodes for Fc (i.e., a heavy chain immunoglobulin sequence), and another lox site (Fig 3). Shen teaches that the sequence flanking the lox sites is recombined with an actively expressed mKate sequence and the hygromycin gene is expressed ([0144]-[0145]), indicating that in the recombined nucleic acid, the hygromycin gene is operably linked to a first promoter.
Shen does not teach that the Fc-encoding gene ends with a polyadenylation sequence.
However, Shen also teaches that the gene-of-interest can also be linked to a polyadenylation sequence ([0037]). Shen teaches transcriptional control sequences liked polyadenylation sites are well known in the art ([0118]-[0119]).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have included a polyadenylation site down stream of the Fc gene of interest. It would have amounted to combining known genetic elements by known means to yield predictable results. The skilled artisan would have been motivated to include a polyadenylation site because Shen suggests it and they are well known in the art to be required for gene expression in mammalian cells.
Regarding claim 2, Shen teaches that there is not a polyA signal sequence between the hygromycin marker and the CMV promoter (Fig 3A).
Regarding claim 4, Shen teaches the CMV promoter is adjacent to Fc (i.e., gene of interest) coding sequence (Fig 3A; [0144]-[0145).
Regarding claim 10, Shen also teaches selection markers that provide a dominant trait and are amplifiable can also be used ([0132]). Shen teaches useful selectable markers for gene amplification include DHFR-MTX resistance ([0133]).
It would have been obvious to one skilled in the art to have substituted the DHFR selectable marker for the hygromycin marker in the nucleic acid construct rendered obvious for claims 1 and 11. It would have amounted to the simple substitution of one known selectable marker for another by known means to yield predictable results. The skilled artisan would have predicted that the DHFR markers could be used because Shen teaches that they are known in the art and are “useful”. Because the prior art recognizes the equivalence of hygromycin and DHFR or GS for the purpose of selecting for integration of an expression cassette into the CHO cell genome, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP 2144.06.II.
Regarding claim 17, Shen teaches the Lox sites are recognized by the Cre recombinase (i.e., the LoxP insertions are a recombinase insertion element that is also an attachment site for the Cre recombinase) (Fig 3A; [0144]-[0145).
Regarding claims 45 and 50, Shen teaches CHO cells comprising one copy of the recombined plasmid according claim 1 above ([0143]-[0145]).
Regarding claim 63, Shen teaches integrating the Fc coding sequence in CHO cells for the purpose of creating CHO cells with high volume production of the recombinant proteins ([0124]).
It would have been obvious to the skilled artisan before the effective filing date of the claimed invention to have purified the Fc fusion protein from the CHO cells comprising the obvious expression cassettes of claim 1 because Shen teaches that is the purpose of creating the recombinant CHO cell lines with the gene encoding the protein of interest.
Regarding claims 69-70, Shen teaches CHO cells comprising the integrated selection marker and gene of interest after recombination with a Cre recombinase that was expressed from a plasmid (i.e., a second nucleic acid construct encoding a recombinase enzyme) ([0144]-[0146]). Because the Fc gene of interest was integrated, the nucleic acid after integration must have existed at the same time the plasmid encoding the Cre recombinase was present (i.e., a system) ([0144]-[0146]).
Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Shen (US 20160115502 A1, published April 28, 2016) as applied to claims 1-2, 4, 10-14, 17, 45, 50, 63 and 69-70 above, and further in view of Skipper (Skipper et al., BMC Biotechnology (2019), 19:75, 1-11).
The teachings of Shen are recited above and applied as for claims 1-2, 4, 10-14, 17, 45, 50, 63 and 69-70.
Shen does not teach transposon insertion elements that are inverted terminal repeats (IRs).
Skipper teaches engineering CHO cells for the long-term expression of transgenes using Sleeping Beauty transposon-mediated genome insertion (Abstract). Skipper teaches a vector comprising two inverted terminal repeats, one positioned 5’ of a promoter sequence and one positioned 3’ of polyA sequence that terminates of a gene of interest (Fig ; page 8, ¶3). Skipper teaches integrating the IR-flanked cassette into the CHO genome using the SB transposon (Fig 1).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have substituted the Cre/Lox system in Shen’s CHO genome integration method for the SB/IR system and further included a promoter into the integration cassette. It would have amounted to the simple substitution of one means of CHO cell integration for another to yield predictable results. The skilled artisan would have predicted that the substitution could be made since both Shen and Skipper teach the systems are functional in CHO cells. Because the prior art recognizes the equivalence of the Cre/Lox system and SB/IR system for the purpose of integrating a gene or interest into a CHO cell, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP 2144.06.II. The skilled artisan would also have had a reasonable expectation that a first promoter could be included in the integration cassette such that the IR’s were position 5’ to a first promoter and 3’ to the poly A sequence because Skipper demonstrates such a cassette. One would have been motivated to have done so for the purpose of controlling expression of the transgene with a heterologous promoter.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Shen (US 20160115502 A1, published April 28, 2016) as applied to claims 1-2, 4, 10-14, 17, 45, 50, 63 and 69-70 above, and further in view of Gaidukov (Gaidukov et al., Nucleic Acids Research (2018), 46: 4072-4086).
The teachings of Shen are recited above and applied as for claims 1-2, 4, 10-14, 17, 45, 50, 63 and 69-70.
Shen does not teach attB integrase sites.
Gaidukov teaches engineering CHO cells for the long-term expression of transgenes using recombinase-mediated genome insertion (Abstract). Gaidukov teaches a vector comprising an attB recombinase attachment site upstream of a puromycin selection marker adjacent to a promoter that is driving expression of an immunoglobulin light chain gene (Figure 3). Gaidukov teaches integrating the Puromycin and light chain coding sequence into the CHO genome using Bxb1 integrase attB/attP integration (Figure 3).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have substituted the Cre/Lox system in Shen’s CHO genome integration method for the Bxb1/attB system. It would have amounted to the simple substitution of one means of CHO cell integration for another to yield predictable results. The skilled artisan would have predicted that the substitution could be made since both Shen and Gaidukov teach the systems are functional in CHO cells. Because the prior art recognizes the equivalence of the Cre/Lox system and BxB1/att system for the purpose of integrating a gene or interest into a CHO cell comprising an already integrating landing pad, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP 2144.06.II.
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, 4, 7-8, 10, 13-14, 17, 45, 50 and 63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12157897 in view of Delenda (Christophe Delenda, Journal of Gene Medicine (2004), 6: S125-S138 and Bennett (US 20040219516 A1).
Patented claim 1 recites A vector for expression of a protein of interest comprising a nucleic acid sequence encoding a selectable marker in operable association with a first promoter sequence and a nucleic acid sequence encoding the protein of interest operably linked to a second promoter sequence, wherein the first promoter sequence is a viral Self-Inactivating (SIN) Long Terminal Repeat (LTR) promoter sequence that is at least 95% identical to SEQ ID NO:3. Patented claims 3-4 recite wherein the selectable marker is Glutamine Synthetase (GS) or Dihydrofolate Reductase (DHFR). Patented claim 6 recites wherein the vector comprises a first poly A signal sequence in operable association with said selectable marker and a second poly A signal sequence in operable association with said nucleic acid encoding the protein of interest. Patented claim 7 recites wherein the protein of interest is selected from the group consisting of an Fc-fusion protein, an enzyme, an albumin fusion, a growth factor, a protein receptor, a single chain antibody (scFv), a single chain-Fc (scFv-Fc), a diabody, and minibody (scFv-CH3), Fab, single chain Fab (scFab), an immunoglobulin heavy chain, and an immunoglobulin light chain. Patented claims 10 and 14 recite A host cell comprising the vector of claim 1, wherein the host cell comprises from about 1 to 1000 copies of the vector. Patented claim 18 recites A process for producing a protein of interest comprising culturing host cells according to claim 10 and purifying the protein of interest from the host cell culture.
The patented claims do not recite the 5’ to 3’ order of the genetic elements of the vector. The patented claims do not recite one or more insertion elements in the vector
Delenda teaches optimization of lentiviral vectors. Delenda teaches the overall structure and modularity of lentiviral vector elements (Fig 3). Delenda teaches an LTR at the 5’ end of the vector (Figure 3).
Bennet teaches a lentiviral vector comprising a 5’ LTR, internal promoters, selectable markers and attR sites (i.e., insertion elements) for the incorporation of additional genetic elements into the lentiviral vector.
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have arranged the elements in the patented vector such that they are 5’ to 3’: LTR promoter – selectable marker – second promoter – GOI – polyA, and included one or more insertion elements 5’ of, 3’ of, or in between the claimed elements. It would have amounted to arranging the patented elements to accommodate the known architecture of lentiviral vectors and including known insertion elements by known means to yield predictable results. The skilled artisan would have been motivated to arrange the patented elements and included attR insertion elements with a reasonable expectation of success because Delenda teaches an LTR is at the 5’ end of lentiviral vectors and Bennett demonstrates attR sites in a lentiviral vector.
Claims 1-2, 7-8, 45, 50 and 63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 34, 37, 38 and 108 of copending Application No. 18007302.
Copending claim 1 recites A host cell comprising a genome, the genome comprising from 1 to 500 integrated docking sites, each docking site comprising at least one dock site insertion element. Copending claims 34, 37 and 38 recite The host cell line of claim 1, further comprising nucleic acid expression constructs inserted at 1 or more of the docking sites, wherein the nucleic acid expression construct further comprises the following elements in operable association in 5' to 3' order: a first promoter sequence; a selectable marker sequence; a second promoter sequence; a nucleic acid sequence encoding a first protein of interest that is operably linked to the internal promoter; and a poly A signal sequence, wherein the nucleic acid construct further comprising at least one insertion element at a position or positions selected from the group consisting of 5' to the first promoter, 3' to the poly A signal sequence, between the first promoter and the poly A signal sequence, between the selectable marker and the second promoter sequence, and both 5' to the first promoter and 3' to the poly A signal sequence. Copending claim 108 recites A process for producing a protein of interest comprising culturing host cells according to claim 34 conditions that the protein of interest is expressed and purifying the protein of interest from the host cell culture. Therefore, the copending claims anticipate examined claims 1-2, 7-8, 45, 50, 63.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowable.
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/CATHERINE KONOPKA/Examiner, Art Unit 1635