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, corresponding to claims 1-13, 15-16 and 23 in the reply filed on 04/20/2026 is acknowledged.
Claims 17, 20 and 26-27 are withdrawn from further consideration pursuant to 37
CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or
linking claim.
Claims 1-13,15-16 and 23 are under examination.
Priority
This application claims priority to GB application GB2212472.1, filed on August 26, 2022.
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.
The file must be submitted in bytes not kilobytes.
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 11 and 15(a) objected to because of the following informalities: the claims read “a nucleic acid sequence of”. The claims should read “the nucleic acid sequence of.” Appropriate correction is required.
Claims 15(b) and 16 are objected to because of the following informalities: the claims read “an amino acid sequence of”. The claims should read “the amino acid sequence of.” Appropriate correction is required.
Claim Interpretation
For purposes of examination, claim 10 is interpreted as the retro viral vector of claim 1, wherein the RNA sequence is less than 9,000 bases in length and comprises a nucleic acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 1.
For purposes of examination, claim 12 is interpreted as the retro viral vector of claim 1, wherein the vector further comprises one or more of:
a p17 protein comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 2.
a p24 protein comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 3.
a p8 protein comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 4.
a protease comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 5.
a p51 comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 6.
a p15 comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 7.
a p31 comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 8.
For purposes of examination, claim 13 is interpreted as the retro viral vector of claim 1, wherein the vector further comprises one or more of:
a Gag protein comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 9 and/or
a Pol protein comprising an amino acid sequence that has at least 80% sequence identity to the entire sequence of SEQ ID NO: 10.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 10, 12, and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Lack of written description for the retroviral vector
Instant claim 10 broadly encompasses an engineered retroviral vector comprising a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1.
The Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to retroviral vector activity, i.e. expressing exogenous genes within a cell.
Regarding claim 10, SEQ ID NO: 1 is 7553 nucleic acids in length. A variant sharing only 80% identity to SEQ ID NO: 1 can have anywhere from 1 to 1511 substitutions, deletions or additions in any combination along any length of the sequence. Thus, just for substitutions with canonical nucleic acids alone, the instant claims encompass an enormous genus (41511 = 2.2 x 103305) comprising trillions upon trillions of sequences.
While the instant claims are drawn to a genus that comprises innumerable permutations of sequences, the Specification has only adequately described and successfully reduced to practice only the exact sequences listed in SEQ ID NO: 1, 19 – 25, and 40 – 44 disclosed in the sequence listing and in the drawings (Figures 1 – 3, and 5 – 7). As such, the Specification reasonably demonstrates that Applicant was in possession of variants having only the exact sequence identity to SEQ ID NO: 1, 19 – 25, and 40 – 44. However, this is not representative of the extremely large genus of sequences claimed, since there is no evidence of the innumerable sequences contained within a genus of sequences having only 80% identical to SEQ ID NO: 1 would function as a retroviral vector.
The data generated for the select variants of the retroviral vectors described in the Specification and Drawings cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of variants thereof because there are no indications that the genus of sequences having at least 80% identity to SEQ ID NO: 1, which includes innumerable permutations, would function as a retroviral vector nor is there a sufficient description of the structure that must be retained for functional characteristics.. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
At best, the Specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Vignuzzi et al (Nat Microbiol, 2019, hereinafter, “Vignuzzi”) evidences that universality and diversity of defective viral genomes and the predicted role of mutations in viral fitness (Abstract). Vignuzzi evidences that “point mutations in RNA viruses can result in detrimental alterations because of the highly constrained nature of their genome organization” and that “a majority of randomly introduced mutations are either lethal or confer a significant fitness cost.” Furthermore, Vignuzzi evidences that detrimental point mutations in different regions of the viral genome can result in widely varying effects from losing the ability from assembling properly, replicating to integrating into the host DNA (Section: Point mutations, hypermutations and frame shifts). The Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to infection of cells let alone the expression of genes within target cells. Thus, one of skill in the art would readily appreciate that single point mutations, truncations, or rearrangements resulting in 80% identity homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least
describe the structural features that are required for the claimed function, in this case the expression of transgenes using a retroviral vector as described in claims 1-13,15-16 and 23.
However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to retroviral vector activity, let alone the various improved properties required throughout the instant claims. The Specification also fails to describe which regions, domains, etc. of the variant sequences must be retained in order to have a functioning variant of the vector. Instead, Applicant merely offers a cursory statement that any variant 80% of SEQ ID NO: 1 will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Lack of written description for the retroviral vector proteins
Instant claim 12 broadly encompasses an engineered retroviral vector comprising amino acid sequences of different encoded proteins having at least 80% sequence identity to SEQ ID NO: 2, 3, 4, 5, 6, 7, and 8, respectively. Instant claim 13 broadly encompasses an engineered retroviral vector comprising amino acid sequences of different encoded proteins having at least 80% sequence identity to SEQ ID NO: 9 and 10 respectively.
The Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to retroviral vector protein function.
Regarding, claim 12, the shortest amino acid sequence listed in the claim is SEQ ID NO: 4 which is 54 amino acids in length. A variant sharing only 80% identity to SEQ ID NO: 4 can have anywhere from 1 to 11 substitutions, deletions or additions in any combination along any length of the sequence. Thus, just for substitutions with canonical nucleic acids alone, the instant claims encompass an enormous genus (2011 = 2.048 x 1014) comprising trillions upon trillions of sequences alone. Factoring the possible inclusion of one or more of SEQ ID NO: 2, 3, 5, 6, 7, and 8 greatly increases the possible number of combinations.
Similarly, for claim 13, the shortest amino acid sequence listed in the claim is SEQ ID NO: 9 which is 519 amino acids in length. A variant sharing only 80% identity to SEQ ID NO: 9 can have anywhere from 1 to 104 substitutions, deletions or additions in any combination along any length of the sequence. Thus, just for substitutions with canonical nucleic acids alone, the instant claims encompass an enormous genus (20104 = 2.028 x 10135) comprising trillions upon trillions of sequences alone. Factoring the possible inclusion of SEQ ID NO: 10 greatly increases the possible number of combinations.
While the instant claims are drawn to a genus that comprises innumerable permutations of sequences, the Specification has only adequately described and successfully reduced to practice only the exact sequences listed in SEQ ID NO: 1 – 46, disclosed in the sequence listing and in the drawings (Figures 1 – 3, and 5 – 7). As such, the Specification reasonably demonstrates that Applicant was in possession of variants having only the exact sequence identity to SEQ ID NO: 1 – 46. However, this is not representative of the extremely large genus of sequences claimed, since there is no evidence of the innumerable sequences contained within a genus of sequences having only 80% identical to SEQ ID NO: 2 – 10 respectively.
The data generated for the select variants of the retroviral vector proteins described in the Specification cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of variants and functional fragments thereof because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
At best, the Specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Moreover, Friedberg (Brief Bioinformatics, 7:225-242 (2006)) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling
of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thorton et al. (Nature Struct. Biol, Struct. Genom. Suppl. Nov., 991-994 (2000), hereinafter “Thorton”) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thorton further describes examples of little correlation between specific enzyme function and overall protein structure (page 992, right column, at lines 2-10). Thus, when taken with the teachings of Friedberg and Thorton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least
describe the structural features that are required for the claimed function, in this case the expression of transgenes using a retroviral vector as described in claims 1-13,15-16 and 23.
However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to retroviral vector activity, let alone the various improved properties required throughout the instant claims. The Specification also fails to describe which regions, domains, etc. of the variant sequences must be retained in order to have a functioning variant of the vector. Instead, Applicant merely offers a cursory statement that any variant 80% of SEQ ID NO: 2 - 10 will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 3, 4, 5, 6, 8, 9, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mitomo et al (Molecular Therapy, 2010, hereinafter, “Mitomo”) as evidenced by Nakajima et al (Human Gene Therapy, 2000, hereinafter, “Nakajima”).
Mitomo discloses a simian immunodeficiency virus (SIV) pseudotyped with envelope proteins from Sendai virus (SeV) (Abstract). Mitomo discloses that this viral vector is efficient at transducing airway epithelial cells and when encoding cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel genes achieves a therapeutic effect that is long lasting, can be administered multiple times, and can be used in a clinical setting (Abstract). Mitomo discloses that the parent virus used to create their viral vector was obtained from Nakajima (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1).
Nakajima evidences the development of multiple viral vectors for human gene therapy (Abstract). Nakajima evidences that a SIV was modified through pseudotyping, inclusion of transgenes, and deletion and modification of SIV ORFs to produce safe viral vectors (Abstract). Nakajima also evidences key retroviral elements and motifs needed for efficient and safe viral vectors (Abstract).
Regarding claims 1, 8, and 9, Mitomo discloses a modified RNA retrovirus that is codon substituted, is comprised of a promoter and transgene, and is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from the respiratory paramoxyvirus SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1,2; Discussion ¶5). Furthermore, Mitomo discloses that the parent gene transfer vector used was created by Nakajima (Section: Production of SIV vector). Nakajima evidences that the SIV parent gene transfer vector removes and combines open reading frames (ORFs) resulting in less ORFs than the wildtype virus (Figure 1, reproduced below). Nakajima evidences the rearrangement and removal of several ORFs to create a viral vector based on SIV such as the truncation and combining of gag, pol, partial vif, and partial vpr genes into a single ORF (Figure 1). Furthermore, Nakajima evidences that the ORF encoding for the envelope is removed and replaced with a chimeric partial vif, partial vpr, tat, and rev ORF (Figure 1). Finally, Nakajima evidences that these two singular ORFs are combined intoa singular ORF resulting in less total ORFs compared to SiV (Figure 1).
Regarding claim 3, Mitomo discloses the respiratory virus is a SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1).
Regarding claim 4, Mitomo discloses the promoter being used is a CMV promoter (Discussion ¶5).
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Regarding claims 5 and 6, Mitomo discloses the transgene used is a CFTR gene (Introduction ¶7; Section: Transduction with F/HN-SIV carrying the CFTR complementary DNA leads to expression of cAMP-dependent chloride channels).
Regarding claim 23, Mitomoto discloses that the retroviral vector was suspended in PBS before administration (Section: Production of SIV vector).
Accordingly, Mitomo, as evidenced by Nakajima, anticipates the claimed invention.
Claim Rejections - 35 USC § 103
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 2 is rejected under 35 U.S.C. 103 as being unpatentable over Mitomo as applied to claims 1, 3, 4, 5, 6, 8, 9, and 23 above, and further in view of Nakajima.
As discussed above, claims 1, 3, 4, 5, 6, 8, 9, and 23 were anticipated by Mitomo.
The reference does not disclose the exact length of RRE used in the retroviral vector.
However, regarding claim 2, Nakajima discloses that the viral vectors’ RRE sequence’s length was modified, which changed expression levels of transgenes (Abstract, Figure 3).
Mitomo and Nakajima are considered to be analogous to the claim invention because they both teach retroviral vectors that can be used for gene therapy. Mitomo discloses a modified RNA retrovirus that is codon substituted, is comprised of a promoter and transgene, and is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from the respiratory paramyxovirus SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1,2; Discussion ¶5). Nakajima discloses that the SIV parent gene transfer vector removes and combines open reading frames (ORFs) resulting in less ORFs than the wildtype virus and with modified RRE lengths (see above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use a partial RRE sequence as taught by Nakajima in a viral vector disclosed by Mitomo because Nakajima teaches that modified RRE sequence improve transgene expression in cells. One of ordinary skill in the art would have had a reasonable expectation of success in using modified RRE sequence in a viral vector as defined by Mitomo given that RRE modifications are known to improve transgene expression in cells, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Mitomo as applied to claims 1, 3, 4, 5, 6, 8, 9, and 23 above, and further in view of Alton et al (Thorax, 2016, hereinafter, “Alton”).
As discussed above, claims 1, 3, 4, 5, 6, 8, 9, and 23 were anticipated by Mitomo.
The reference does not disclose a retroviral vector encoding both a hCEF promoter and a CTFR transgene.
However, Alton discloses using a SIV pseudotyped with HN and F proteins encoding a codon optimized CFTR driven by hCEF in preparation for patients diagnosed with cystic fibrosis (Abstract, Generation of pharmacopoeia-compliant producer plasmid). Alton discloses that gene therapy using this construct led to high transduction efficiency and acceptable toxicity (Abstract). Furthermore, Alton discloses the modification of the viral vector used by Mitomo to achieve the hCEF driven viral vector (Materials and Methods: Section Generation of pharmacopoeia-compliant producer plasmid).
Regarding claim 7, Alton discloses the generation and use of a SIV vector pseudotyped with HN and F proteins from SeV that drives a codon optimized CFTR with hCEF (Section: CFTR expression and function after rSIV.F/HN-hCEF-CFTR transduction).
Mitomo and Alton are considered to be analogous to the claim invention because they both teach retroviral vectors that can be used for gene therapy. Mitomo discloses a modified RNA retrovirus that is codon substituted, is comprised of a promoter and transgene, and is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from the respiratory paramyxovirus SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1,2; Discussion ¶5). Alton discloses the generation and use of a SIV vector pseudotyped with HN and F proteins from SeV that drives a codon optimized CFTR with hCEF (Section: CFTR expression and function after rSIV.F/HN-hCEF-CFTR transduction).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to encode both a hCEF and a CTFR transgene, as taught by Alton, in a viral vector disclosed by Mitomo because the exact combination is known to be efficient transgene expression within certain cell types. One of ordinary skill in the art would have had a reasonable expectation of success in encode both a hCEF and a CTFR tansgene in a viral vector given that the combination of hCEF and CTFR transgene in a pseudotyped SIV viral vector is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary
Claim 12 are rejected under 35 U.S.C. 103 as being unpatentable over Mitomo as applied to claims 1, 3, 4, 5, 6, 8, 9, and 23 above, and further in view of Haynes (US20120213817A1, hereinafter, “Haynes”).
As discussed above, claims 1, 3, 4, 5, 6, 8, 9, and 23 were anticipated by Mitomo.
The reference does not disclose the exact sequence of the p17 sequence as defined in SEQ ID NO: 2.
However, Haynes teaches chimeric virus like particles (VLPs) comprised of lentiviruses and RSV (Abstract). Haynes teaches that SIV p17 can be used in multiple chimeric VLPs (¶0001, Figure 32). Furthermore, Haynes teaches the use of chimeric VLPs to immunize subjects by delivering the VLP to the lung (¶0349, Figure 42).
Regarding claim 12, Haynes teaches the exact sequence of SEQ ID NO: 2 encoding the p17 protein (reproduced below, Qy is SEQ ID NO: 2, Db is Haynes).
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Mitomoand Haynes are considered to be analogous to the claim invention because they all teach compositions that can be used for gene therapy. Mitomo discloses a modified RNA retrovirus that is codon substituted, is comprised of a promoter and transgene, and is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from the respiratory paramoxyvirus SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1,2; Discussion ¶5). Haynes teaches the exact sequence of SEQ ID NO: 2 encoding the p17protein (see above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use the exact p17 sequence taught by Haynes in a viral vector disclosed by Alton because this exact p17 sequence improves viral stability. One of ordinary skill in the art would have had a reasonable expectation of success in using a the exact p17 sequence as SEQ ID NO: 2 in a viral vector as defined by Alton given that the p17 sequence and use in other VLPs is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Mitomo as applied to claims 1, 3, 4, 5, 6, 8, 9, and 23 above, and further in view of Fukasawa (Nature, 1988, hereinafter, “Fukasawa”).
As discussed above, claims 1, 3, 4, 5, 6, 8, 9, and 23 were anticipated by Mitomo.
The references do not disclose the exact sequence of the Gag sequence as defined in SEQ ID NO: 9.
However, Fukasawa teaches the sequence of SIV (Abstract). Fukasawa teaches that SIV is found in wild Afircan green monkey of Kenyan Origin (Abstract). Furthermore, Fukasawa teaches that this SIV is related to HIV Abstract).
Regarding claim 13, Fukasawa teaches a 99.8% sequence identity of SEQ ID NO: 9 encoding the Gag protein (reproduced below, Query is SEQ ID NO: 9, Sbjct is Fukasawa).
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Mitomoand Fukasawa are considered to be analogous to the claim invention because they all teach compositions that include SIV. Mitomo discloses a modified RNA retrovirus that is codon substituted, is comprised of a promoter and transgene, and is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from the respiratory paramoxyvirus SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1,2; Discussion ¶5). Fukasawa teaches 99.8% sequence identity of SEQ ID NO: 9 encoding the Gag protein (see above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use the exact Gag sequence taught by Fukasawa in a viral vector disclosed by Alton because this Gag sequence is important for viral structure. One of ordinary skill in the art would have had a reasonable expectation of success in using the Gag sequence as taught by Fukasawa in a viral vector as defined by Alton given that the Gag sequence and use in other SIV is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1 – 9, and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, and 5 of U.S. Patent No. US10704061B2 in view of Mitomo as evidenced by Nakajima.
Instant claim 1, 8, and 9 are drawn to a codon substituted, reduced ORFs, SIV RNA retroviral sequence comprising a promoter and a transgene that is pseudotyped with HN and F proteins from a respiratory paramyxovirus. U.S. Patent ‘061 claim 1 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a respiratory paramyxovirus with a promoter. U.S. Patent ‘061 claims 3 and 5 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a respiratory paramyxovirus encoding a transgene.
‘061 does not explicitly teach a codon substituted viral vector or a reduced number of ORFs.
However, Mitomo discloses a simian immunodeficiency virus (SIV) pseudotyped with envelope proteins from Sendai virus (SeV) (Abstract). Mitomo discloses that this viral vector is efficient at transducing airway epithelial cells and when encoding cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel genes achieves a therapeutic effect that is long lasting, can be administered multiple times, and can be used in a clinical setting (Abstract). Mitomo discloses that the parent virus used to create their viral vector was obtained from Nakajima (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1).
Nakajima evidences the development of multiple viral vectors for human gene therapy (Abstract). Nakajima evidences that a SIV was modified through pseudotyping, inclusion of transgenes, and deletion and modification of SIV ORFs to produce safe viral vectors (Abstract). Nakajima also evidences key retroviral elements and motifs needed for efficient and safe viral vectors (Abstract).
Regarding instant claims 1, 8, and 9, Mitomo discloses a modified RNA retrovirus that is codon substituted, is comprised of a promoter and transgene, and is pseudotyped with hemagglutinin-neuraminidase (HN) and fusion (F) proteins from the respiratory paramoxyvirus SeV (Section: F/HN-pseudotyped SIV vectors can be generated and produced at high titers ¶1,2; Discussion ¶5). Furthermore, Mitomo discloses that the parent gene transfer vector used was created by Nakajima (Section: Production of SIV vector). Nakajima evidences that the SIV parent gene transfer vector removes and combines open reading frames (ORFs) resulting in less ORFs than the wildtype virus (Figure 1, reproduced below). Nakajima evidences the rearrangement and removal of several ORFs to create a viral vector based on SIV such as the truncation and combining of gag, pol, partial vif, and partial vpr genes into a single ORF (Figure 1). Furthermore, Nakajima evidences that the ORF encoding for the envelope is removed and replaced with a chimeric partial vif, partial vpr, tat, and rev ORF (Figure 1). Finally, Nakajima evidences that these two singular ORFs are combined intoa singular ORF resulting in less total ORFs compared to SiV (Figure 1).
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Together, , Mitomo as evidenced by Nakajima,teach that the pseudotyped lentivirus can be codon substituted and contain a reduced number of ORFs. Thus, both instant claim 1 and U.S. Patent ‘061 claims 1, 3, and 5, in view of Mitomo as evidenced by Nakajima, are drawn to a pseudotyped lentivirus as described in instant claim 1, 8, and 9.
Instant claim 3 is drawn to a codon substituted, reduced ORFs, RNA retroviral sequence comprising a promoter and a transgene that is pseudotyped with HN and F proteins from a respiratory paramyxovirus further limited to a SeV. ‘061 claim 4 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a SeV. Thus, both instant claim 4 and U.S. Patent ‘061 claims 4, in view of Mitomo as evidenced by Nakajima, are drawn to a pseudotyped lentivirus as described in instant claim 1 pseudotyped with SeV proteins.
Instant claim 4 is drawn to a codon substituted, reduced ORFs, RNA retroviral sequence comprising a promoter and a transgene that is pseudotyped with HN and F proteins from a respiratory paramyxovirus further limited to include a hCEF promoter. ‘061 claim 1 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a respiratory paramyxovirus with a hCEF promoter. Thus, both instant claim 4 and U.S. Patent ‘061 claims 1, in view of Mitomo as evidenced by Nakajima, are drawn to a pseudotyped lentivirus as described in instant claim 1 with a hCEF promoter.
Instant claims 5 and 6 are drawn to a codon substituted, reduced ORFs, RNA retroviral sequence comprising a promoter and a transgene that is pseudotyped with HN and F proteins from a respiratory paramyxovirus further limited to include a CFTR transgene. ‘061 claim 5 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a respiratory paramyxovirus with a CFTR transgene. Thus, both instant claim 5 and 6 and U.S. Patent ‘061 claims 5, in view of Mitomo as evidenced by Nakajima, are drawn to a pseudotyped lentivirus as described in instant claim 1 with a CFTR transgene.
Instant claim 7 is drawn to a codon substituted, reduced ORFs, RNA retroviral sequence comprising a promoter and a transgene that is pseudotyped with HN and F proteins from a respiratory paramyxovirus further limited to include a hCEF promoter and a CFTR transgene. ‘061 claim 1 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a respiratory paramyxovirus with a hCEF promoter. ‘061 claim 5 is drawn to a lentivirus vector pseudotyped with HN and F proteins from a respiratory paramyxovirus with a CFTR transgene.
Thus, both instant claim 5 and 6 and U.S. Patent ‘061 claims 1 and 5, in view of Mitomo as evidenced by Nakajima, are drawn to a pseudotyped lentivirus as described in instant claim 1 with a CFTR transgene.
Conclusion
NO CLAIMS ARE ALLOWED
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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