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 .
Priority
This application is a divisional application (DIV) of U.S. Application Serial Number 17/584,508, filed 1/26/2022, which is a DIV of U.S. Application Serial Number 16/313,060, filed 12/24/2018, which is a 371 of PCT/IL2017/050731, filed 6/29/2017. This application claims benefit to U.S. Provisional Application Serial Number 62/355,898, filed 6/29/2016. Claims 1-20 are pending and have been examined on the merits.
Note: The instant claims are not drawn to the non-elected invention from the restriction requirement mailed 5/3/2023 for the 17/584,508 application (parent application of instant application) because the instant claims are drawn to methods of transcriptional modulation or genome editing in a host cell, while the non-elected invention from the restriction requirement mailed 5/3/2023 for the 17/584,508 application is drawn to methods of administering a polypeptide wherein no transcriptional modulation or genome editing is recited or suggested; hence, the instant claims have been rejected on the ground of nonstatutory double patenting over US 12070476 (from 17/584508 application) and over US 11260081 (from 16/313060 application) as set forth on pp. 14-19 below.
Information Disclosure Statement
The information disclosure statements submitted on 9/4/2024, 4/9/2025, 6/17/2025 and 1/29/2026 have been considered by the examiner.
Claim Objections
Claims 1, 4-5, 7-8 and 15-20 are objected to because of the following informalities:
Claim 8, lines 2-3, recites “Toxoplasma gondii” which should be “Toxoplasma gondii” because taxonomic names are italicized.
Claim 1, lines 2, 4, 7, 9; claim 4, line 1; claim 5, line 1; claim 7, line 1; claim 15, line 3; claim 16, line1; claim 17, lines 1-2; claim 18, line 1; claim 19, line 1 and claim 20, line 1 recite “Toxoplasma” which should be “Toxoplasma” because taxonomic names are italicized.
Claim 19 recites “in-vivo” which should be italicized - “in vivo”.
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.
Claim 9 is 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 9 recites the limitation "wherein said dense granule comprises" in line 1. There is insufficient antecedent basis for this limitation in the claim. It would appear that the phrase should be "wherein said dense granule protein comprises" because claim 9 depends from claim 8 and claim 8 recites “a dense granule protein”.
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.
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, 4-6, 16 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Koshy et al., 2012 (cite U, attached PTO-892; herein “Koshy”).
Koshy teaches methods of genome editing in a host cell comprising contacting Cre-reporter cells or animals, i.e., contacting the host cell, with a Toxoplasma gondii transformed with a nucleic acid construct comprising a heterologous polynucleotide expressing a rhoptry:Cre recombinase fusion protein wherein the rhoptry protein is toxofilin under the control of the toxofilin promoter, i.e., comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein which is a rhoptry protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical agent for genome editing, i.e., Cre recombinase, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma wherein said promoter is a Toxoplasma endogenous promoter, wherein said Toxoplasma secreted protein is secreted to the host cell (Abst.; pp. 11-12, “Generation and selection of Cre- and -b-lactamase-secreting Toxoplasma”; pp. 12-13, “Evaluation of rhoptry secretion using Cre-reporter cells”; p. 13, “Infection of Cre-reporter mice”).
Hence, Koshy only differs from the method of claim 1 in that claim 1 recites “with the proviso that said promoter is not a Toxofilin promoter”; thus, excluding the construct in Koshy.
However, Koshy further teaches that the Toxoplasma are also transfected with nucleic acid constructs expressing reporter proteins (mCherry) under the control of the GRA2 promoter or the GRA1 promoter (pp. 11-12, “Generation and selection of Cre- and -b-lactamase-secreting Toxoplasma”).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of Koshy wherein the promoter driving the rhoptry:Cre recombinase fusion protein expression is the GRA2 promoter or the GRA1 promoter with a reasonable expectation of success because Koshy teaches that the GRA2 promoter and the GRA1 promoter function in Toxoplasma at the time that the rhoptry:Cre recombinase fusion protein is expressed; therefore, claims 1, 4-6, 16 and 19 are prima facie obvious.
Regarding claim 16, the Toxoplasma in Koshy can be derived from Toxoplasma RH, an unattenuated strain (pp. 11-12, “Generation and selection of Cre- and -b-lactamase-secreting Toxoplasma”); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Koshy wherein the Toxoplasma is not attenuated; therefore, claim 16 is prima facie obvious.
Regarding claim 19, Koshy performs the method in vivo (p. 13, “Infection of Cre-reporter mice”); hence, claim 19 is prima facie obvious.
Regarding claim 4, Koshy teaches that the Toxoplasma strain can be an encysting strain (pp. 11-12, “Generation and selection of Cre- and -b-lactamase-secreting Toxoplasma”); hence, a person of ordinary skill in the art at the time of filing would have found it obvious that said Toxoplasma persists in said host cell following infection; therefore, claim 4 is prima facie obvious.
Claims 1, 4-9, 12, 14 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Koshy in view of Blanchard et al., WO 2016/046321 (Foreign Patent Document cite 10; herein “Blanchard”).
The discussion of Koshy regarding claims 1, 4-6, 16 and 19 set forth in the rejection above is incorporated herein.
As discussed above, Koshy makes obvious methods of genome editing in a host cell comprising contacting the host cell with a Toxoplasma gondii transformed with a nucleic acid construct comprising a heterologous polynucleotide construct comprising a Toxoplasma endogenous promoter, which is not the toxofilin promoter, expressing a rhoptry:Cre recombinase fusion protein wherein the rhoptry is toxofilin, i.e., comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein which is a rhoptry protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical agent for genome editing, i.e., Cre recombinase, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma wherein said promoter is a Toxoplasma endogenous promoter, wherein said Toxoplasma secreted protein is secreted to the host cell, but Koshy does not specifically teach using a non-rhoptry secreted protein as the N-terminal part of the fusion protein. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the Toxoplasma secreted protein on which the fusion protein is based to be the dense granule protein, GRA6, in view of the disclosure of Blanchard.
Blanchard, like Koshy, teaches transforming Toxoplasma with nucleic acid constructs which comprise a heterologous nucleic acid encoding a fusion protein of a Toxoplasma secreted protein and a pharmaceutical protein (Abst.). Blanchard teaches that the Toxoplasma secreted protein can be GRA6, a dense granule protein comprising the amino acid sequence of instant SEQ ID NO: 249 (Abst.).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Koshy wherein the Toxoplasma secreted protein comprising the N-terminal part of the fusion protein is GRA6, because Blanchard discloses transforming Toxoplasma with nucleic acid constructs which comprise a heterologous nucleic acid encoding a fusion protein of GRA6 and a pharmaceutical protein wherein administration of the Toxoplasma is effective for delivering the pharmaceutical protein to a subject in need thereof for the treatment of cancer or infectious diseases (Abst.); therefore, claims 7-9 are prima facie obvious.
Blanchard further teaches that the transformed Toxoplasma can comprise nucleic acid for the negative selection marker thymidine kinase (p. 7, full ¶1). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the nucleic acid construct to further comprise a third nucleic acid sequence encoding thymidine kinase; therefore, claims 12 and 14 are prima facie obvious.
Because cells comprising the thymidine kinase gene can be killed by treatment with ganciclovir which is harmless to cells which are not expressing thymidine kinase, under a broadest reasonable interpretation, the thymidine kinase gene constitutes an inducible self-destruction element wherein the inducible self-destruction element is active in response to a drug, i.e., ganciclovir.
Blanchard teaches that their methods, which encompass administration to human subjects (p. 19, ll. 31-33), use attenuated Toxoplasma (Abst.). Blanchard teaches that the Toxoplasma can be attenuated such that their replication in cells is blocked (p. 7, ll. 11-19); therefore, claim 17 is prima facie obvious.
Regarding claims 18 and 20, Blanchard discloses attenuating the Toxoplasma for use in human subjects; hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the Toxoplasma are devoid of virulence genes which are not necessary for delivery of said pharmaceutical polypeptide into the host cell, into a central nervous system (CNS) or a muscle tissue of a subject; therefore, claims 18 and 20 are prima facie obvious.
Claims 1, 4-10, 12, 14 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Koshy in view of Blanchard and Hu et al., 2015 (NPL cite 40, IDS, 9/4/2024; herein “Hu”).
The discussion of Koshy and Blanchard regarding claims 1, 4-9, 12, 14 and 16-20 set forth in the rejection above is incorporated herein.
Blanchard discloses transformed Toxoplasma which secrete fusion proteins comprising the dense granule protein, GRA6, for the N-terminal part of the fusion protein but Blanchard does not disclose that the dense granule protein is GRA16 or GRA24; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the dense granule protein in the method made obvious by Koshy in view of Blanchard to be GRA16 or GRA24 in view of the disclosure of Hu.
Hu teaches that Toxoplasma gondii comprises the dense granule proteins GRA16 and GRA24 (p. 665). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the dense granule protein used in the method made obvious by Koshy in view of Blanchard to form the fusion protein could be GRA16 or GRA24 in place of GRA6 with a reasonable expectation of success; therefore, claim 10 is prima facie obvious.
Claims 1, 4-12, 14 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Koshy in view of Blanchard, Hu and Sibley et al., 2011 (NPL cite 44, IDS, 9/4/2024; herein “Sibley”)
The discussion of Koshy, Blanchard and Hu regarding claims 1, 4-10, 12, 14 and 16-20 set forth in the rejection above is incorporated herein.
Koshy makes obvious methods of genome editing in a host cell comprising contacting the host cell with a Toxoplasma gondii transformed with a nucleic acid construct comprising a Toxoplasma endogenous promoter, which is not the toxofilin promoter, expressing a fusion protein of a Toxoplasma-secreted protein fused to a genome editing protein wherein the genome editing protein is Cre recombinase and wherein the Toxoplasma-secreted protein is toxofilin, a rhoptry protein; Blanchard makes obvious that the Toxoplasma-secreted protein can be the dense granule protein GRA6; and Hu makes obvious that the Toxoplasma-secreted protein can be the dense granule proteins GRA16 or GRA24 as set forth in the rejections above, but none disclose that the Toxoplasma-secreted protein can be a microneme protein comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 280-322. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the Toxoplasma-secreted protein to be the microneme protein MIC2, which is instant SEQ ID NO: 301, or the microneme protein AMA1, which is instant SEQ ID NO: 282 in view of the disclosure of Sibley.
Sibley discloses that microneme proteins MIC2 and AMA1 are discharged, i.e., secreted, during Toxoplasma invasion of the host cell (p. 7); hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the Toxoplasma-secreted protein in the method made obvious by Koshy can be MIC2 (SEQ ID NO: 301) or AMA1 with a reasonable expectation of success; therefore, claim 11 is prima facie obvious.
Claims 1, 4-12 and 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Koshy in view of Blanchard, Hu, Sibley and Kahn, US 5693325 (US Patent Document cite 6, IDS, 9/4/2024; herein “Kahn”).
The discussion of Koshy, Blanchard, Hu and Sibley regarding claims 1, 4-12, 14 and 16-20 set forth in the rejection above is incorporated herein.
None of the references specifically recite that the expressed fusion protein comprises at least one in frame cleavage site which allows detachment of said pharmaceutical polypeptide from said Toxoplasma secreted protein. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the fusion protein in the method made obvious by Koshy to further comprise a cleavage site which allows detachment of said pharmaceutical polypeptide from said Toxoplasma secreted protein in view of the disclosure of Kahn.
Kahn teaches therapeutic proteins comprising two functional parts joined by a cleavable linker (Abst.) wherein the cleavable linker can be, e.g., a Cathepsin D recognition site (col. 21, ll. 28-34).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the method made obvious by Koshy to further comprise engineering a cleavable linker between the Toxoplasma secreted protein and the genome engineering polypeptide with a reasonable expectation of success; therefore, claim 15 is prima facie obvious.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Koshy in view of Blanchard, Hu, Sibley Kahn and Sanjana et al., 2012 (cite U, attached PTO-892; herein “Sanjana”).
The discussion of Koshy, Blanchard, Hu and Sibley regarding claims 1, 4-12 and 14-20 set forth in the rejection above is incorporated herein.
Koshy makes obvious methods of genome editing in a host cell comprising contacting the host cell with a Toxoplasma gondii transformed with a nucleic acid construct comprising a Toxoplasma endogenous promoter, which is not the toxofilin promoter, expressing a fusion protein of a Toxoplasma-secreted protein fused to a genome editing protein wherein the genome editing protein is Cre recombinase, but Koshy does not specifically recite using a different transcriptional modulation or genome editing polypeptide as part of the expressed fusion protein. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the transcription modulating or genome editing polypeptide in Koshy’s fusion polypeptide to be TALE transcription factors or nucleases in view of the disclosure of Sanjana.
Sanjana discloses that transcription activator-like effectors (TALEs) are a class of naturally occurring DNA-binding proteins found in the plant pathogen Xanthomonas sp.; that the DNA-binding domain of each TALE consists of tandem 34-amino acid repeat modules that can be rearranged according to a simple cipher to target new DNA sequences; and that customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing (Abst.).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the method of Koshy for genome editing in a host cell can be modified to express a fusion protein comprising a Toxoplasma-secreted protein fused to a genome editing or transcription modulating protein wherein the genome editing or transcription modulating protein is a TALE transcription factor (TALE TF) or a TALE nuclease (TALEN); therefore, claims 2-3 and 13 are prima facie obvious.
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 and 4-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-10, 13-16 of U.S. Patent No. 11260081 (“’081” herein) in view of Koshy.
Claim 1 of ‘081 recites a method of administering a protein-of-interest into a central nervous system of a subject, the method comprising: administering to the subject a Toxoplasma transformed with a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a Toxofilin promoter, wherein said toxoplasma secreted protein is secreted to a host cell, and wherein said toxoplasma secreted protein is selected from the group consisting of a rhoptry secreted protein, a microneme protein, a dense granule protein and a Toxoplasma gondii macrophage migration inhibitory factor (TgMIF), and wherein said dense granule protein is selected from the group consisting of GRA16 and GRA24, thereby administering the protein-of-interest to the central nervous system of the subject.
‘081 does not recite that the protein-of-interest is a pharmaceutical agent for transcriptional modulation or genome editing; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the protein-of-interest to be a pharmaceutical agent for transcriptional modulation or genome editing in view of the disclosure of Koshy, discussed in detail on pp. 5-7 above; therefore, instant claim 1 is prima facie obvious over claim 1 of ‘081 in view of Koshy.
Instant claims 4-20 are prima facie obvious over claims 4, 9-10, 13-16 of ‘081 in view of Koshy.
Claims 1 and 4-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12070476 (“’476” herein) in view of Koshy.
Claim 1 of ‘476 recites a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein said Toxoplasma secreted protein is secreted to a host cell when infected by the Toxoplasma, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a Toxofilin promoter.
Claim 1 of ‘476 does not teach a method of transcriptional modulation or genome editing in a host cell; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice a method of transcriptional modulation or genome editing in a host cell with the nucleic acid constructs and transformed Toxoplasma recited in claims 1-18 of ‘476 in view of the disclosure of Koshy.
Koshy teaches methods of genome editing in a host cell comprising contacting Cre-reporter cells or animals, i.e., contacting the host cell, with a Toxoplasma gondii transformed with a nucleic acid construct comprising a heterologous polynucleotide expressing a rhoptry:Cre recombinase fusion protein wherein the rhoptry is toxofilin under the control of the toxofilin promoter, i.e., comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein which is a rhoptry protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical agent for genome editing wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma wherein said promoter is a Toxoplasma endogenous promoter, wherein said Toxoplasma secreted protein is secreted to the host cell (Abst.; pp. 11-12, “Generation and selection of Cre- and -b-lactamase-secreting Toxoplasma”; pp. 12-13, “Evaluation of rhoptry secretion using Cre-reporter cells”; p. 13, “Infection of Cre-reporter mice”).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice a method of transcriptional modulation or genome editing in a host cell, comprising contacting the host cell with a Toxoplasma transformed with a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical agent for transcriptional modulation or genome editing, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a Toxofilin promoter, wherein said Toxoplasma secreted protein is secreted to the host cell because Koshy demonstrates that the nucleic acid constructs and transformed Toxoplasma recited in claims 1-18 of ‘476 can be used for said method wherein the pharmaceutical polypeptide is a recombinase; therefore, instant claim 1 is prima facie obvious.
Instant claims 4-20 are prima facie obvious over claims 1-18 of ‘476 in view of Koshy.
Conclusion
No claims are allowed.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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