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 103 – 118 and 120 in the reply filed on 03/27/2026 is acknowledged. Examiner also acknowledges applicant’s election of species:
Species I: Amino Acid Sequence for a Viral Structural Protein – SEQ ID NO: 2
Species II: Heterologous Molecule of Interest – CAR
Species III: Amino Acid Sequence for CAR – SEQ ID NO: 52
Species IV: Moiety Target – CD7 + T-Cell
Species V: Means of Attaching the Targeting Moiety – IgG Fc stalk
Species VI: Amino Acid Sequence of a Targeting Moiety – SEQ IN NO:28
Claims 116, 119, 121, and 122 are withdrawn from further consideration pursuant to 37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 103 – 115, 117, 118, and 120 are under examination.
Priority
This application claims priority to US provisional application 63/267870, filed on February 11, 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 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 103 – 115, 117, 118, and 120 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.”
I. Lack of written description for an innumerable combination of amino acids corresponding to a viral structural protein
The claims are broadly drawn to a genus comprising: an amino acid sequence that is at least 90%, 95%, or 98% identical to SEQ ID NO: 2. However, 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 protein function. There is not sufficient description of the structural features that must be retained to establish a functional relationship with respect to viral envelope stability and viral tropism.
The broadest reasonable interpretation of the claims encompasses innumerable permeations of the proteins of SEQ ID NO: 2. The Specification fails to disclose which regions of SEQ ID NO: 2 can be mutated, deleted, truncated, etc., or which regions of SEQ ID NO: 2 must be retained with respect to function. The claims improperly define the genus based on what it does—not what it is.
SEQ ID NO: 2 is 491 amino acids in length. A variant sharing 90% identity to SEQ ID NO: 2 can have anywhere from 1 to 49 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 2049 = 5.63 x 1063) comprising trillions upon trillions of sequences.
While the claims are drawn to a nebulous genus of ill-defined variants, the Specification has only adequately described and successfully reduced to practice specific 7 different viral structural proteins (Figure 1, Figure 2, ¶124).
At best, the Specification contemplates the use of BLAST to identify functional homologs based on sequence homology (¶0033). 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, with regards to SEQ ID NO: 2, viral envelope stability and viral tropism.
However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to function, let alone the various improved properties required throughout the instant claims. Applicant merely offers a cursory statement that any amino acid sequence with 90% identity to SEQ ID NOs: 2, 28, or 52 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 before the effective filing date of the claimed invention.
II. Lack of written description for CAR
Claims 109 and 120 broadly encompasses a CAR comprising an antigen binding domain with at least 90% sequence identity to SEQ ID NO: 52, with claim 120 limiting the sequence identity to 95% or 98%. There is not sufficient description of the structural features that must be retained to establish a functional relationship with respect to producing a functional and stable chimeric antigen receptor (CAR).
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 the ability of the antigen-binding protein to bind to the CAR. The claims define the CAR based on what it does—not what it is. Additionally, 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 the ability of the antigen-binding protein to bind to the CAR. There are no structural limitations assigned to the CAR and does not establish a structure-function relationship with the ability to bind to an antigen. As such, the claim describes a countless amount of CARs thereof.
SEQ ID NO: 52 is 244 amino acids in length. A variant sharing 90% identity (the most restrictive scenario) to SEQ ID NO: 52 can have anywhere from 1 to 24 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 (2024 = 1.68 x 1031) comprising trillions upon trillions of sequences.
While the instant claims are drawn to a genus that comprises innumerable number of CAR, the Specification has only adequately described and successfully reduced to practice a singular CAR (Figure 2, 4, and 5). However, this is not representative of the extremely large genus of CAR claimed.
The data generated for the select antibodies described in the Specification and Drawings cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of CARs because no structure-function relationship is established as to amino acid sequence and function 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).
Moreover, Manning et al (Immunity, 1998, 10.1016/s1074-7613(00)80547-6, hereinafter, “Manning”) teaches that highly similar CAR structures do not result in predictable function. Manning teaches the antigen recognition site plays a key role in the target affinity of an antigen, showing that even a single amino acid alteration in the antigen recognition site can result in loss of antigen-binding function (Figure 2, Table 2). Because the properties and function of a CAR are highly dependent upon the amino acid sequences of CDRs, wherein, even one amino acid difference in a CDR region leads to different functional properties, different conformations of CDR sequences would result in CARs having different properties. Thus, when taken with the teachings of Manning, one of skill in the art would readily appreciate that mere knowledge of structure alone cannot serve as the basis to describe members of the genus that have the recited function because a single CAR’s structure is unpredictable.
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 amino acid sequences vital to antigen binding to a CAR. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to CAR epitope binding activity. The Specification also fails to describe which regions, domains, etc. of the CAR sequences must be retained in order of antigen recognition. Instead, Applicant merely offers a cursory statement that any antibody or antigen-binding fragment that binds to a CAR epitope 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.
III. Lack of written description for targeting moiety
Claim 120 broadly encompasses a targeting moiety that is an antibody or antigen-binding polypeptide (¶0113). There is not sufficient description of the structural features that must be retained to establish a functional relationship with respect to targeting cell types.
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 the ability of the antibody-binding polypeptide or antibody to bind to its target protein such as CD7. The claims define the protein based on it does—not what it is. Additionally, 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 the binding to the target protein.
The claim recites a targeting moiety with 90%, 95%, and 98% sequence identity to SEQ ID NO: 28 which alone encompasses a large amount of proteins as there are no structural limitations assigned to the protein and does not establish a structure-function relationship with the ability to bind to a target antigen, in this case CD7.
SEQ ID NO: 28 is 249 amino acids in length. A variant sharing 90% identity (the most restrictive scenario) to SEQ ID NO: 28 can have anywhere from 1 to 24 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 (2024 = 1.68 x 1031) comprising trillions upon trillions of sequences. Accounting for SEQ ID NO: 2 (2049 = 5.63 x 1063) and SEQ ID NO: 52 (2024 = 1.68 x 1031) would result in trillions upon trillions more combinatorial sequences for substitutions alone.
While the instant claims are drawn to a genus that comprises innumerable number of antibodies or antigen binding polypeptides, the Specification has only adequately described and successfully reduced to practice 2 targeting moieties (Figure 2, 4, and 5, ¶0118). However, this is not representative of the extremely large genus of antibodies or antigen binding polypeptides claimed.
The data generated for the select antibodies described in the Specification and Drawings cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of antibodies and antigen-binding polypeptides thereof because no there is no defined portion of the amino acid sequence that accounts for the structure 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).
Moreover, Rudikoff et al (PNAS, 1982, hereinafter, “Rudikoff”) teaches that highly similar antibody structures do not result in predictable function. Rudikoff teaches the CDR plays a key role in the target affinity of an antibody, showing that even a single amino acid alteration in the CDR can result in loss of antigen-binding function (Section: Implications for Generation of Diversity). Because the properties and function of an antibody are highly dependent upon the amino acid sequences and exact combination of CDRs, wherein, even one amino acid difference in a CDR region leads to different functional properties, different conformations of CDR sequences would result in antibodies or antigen-binding fragments having different properties. Furthermore, Einav et al (bioRxiv, 2020, hereinafter, “Einav”) teaches models of antibody mixtures through simulation. Einav teaches that even though models can be used to account for to help predict the activity of antibody mixtures, it can be “difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized” (Abstract). Thus, when taken with the teachings of Rudikoff and Einav, one of skill in the art would readily appreciate that mere knowledge of structure alone cannot serve as the basis to describe members of the genus that have the recited function because a single antibody’s or antigen-binding polypeptide’s structure is unpredictable.
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 binding to a target protein. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to epitope binding activity. The Specification also fails to describe which regions, domains, etc. of the antibody sequences must be retained in order to bind to the target protein such as CD7. Instead, Applicant merely offers a cursory statement that any antibody or antigen-binding poly peptide that binds to an epitope 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 § 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.
Claims 103, 105, 106, 113, 114, 117, and 118, are rejected under 35 U.S.C. 103 as being unpatentable over Taube et al (PLOS one, 2008, 10.1371/journal.pone.0003181, hereinafter, “Taube”), in view of Charneu et al (US20100297168A1, hereinafter, “Charneu”).
Taube teaches pseudotyped lentiviral vectors that are comprised of a single-chain variable region antibody fragments (scFv) and foreign viral glycoproteins (G proteins) (Abstract, Section: Generation of scFvFc-TM/VSV-G pseudotyped lentiviruses and 293T cells stably expressing scFvFc-TM through lentiviral transduction). Taube teaches the optimization of transmembrane domains, targeting moieties, and G proteins for lentivirus to achieve high-level expression in human cells to allow for binding of cognate antigens (Figures 3- 7). Furthermore, Taube teaches that these viral constructs can be generated in high titers and can be used to screen for antibodies (Discussion ¶7).
Charneau teaches pseudotyped lentiviral vectors that are used for in-vivo administration into a host (Abstract). Charneu teaches that lentivirus pseudotyped with G-proteins affect tropism and can affect viral stability (¶0078). Charneu also teaches that the G protein of Spring viremia of carp virus (SVCV) can be used to pseudotype lentivirus (¶0098).
Regarding claim 103, Taube teaches pseudotyped lentiviral vectors that are comprised of a single-chain variable region antibody fragments (scFv) and foreign viral glycoproteins (G proteins) (Abstract, Section: Generation of scFvFc-TM/VSV-G pseudotyped lentiviruses and 293T cells stably expressing scFvFc-TM through lentiviral transduction). Taube does not teach an amino acid sequence that is at least 90% identical to SEQ ID NO: 2. However, Charneau teaches an amino acid sequence for a SVCV G protein that is 96% identity to SEQ ID NO:2 (Reproduced below, Qy is SEQ ID NO: 2, Db is Charneau).
RESULT 6
US-12-671-898-28
(NOTE: this sequence has 2 duplicates in the database searched)
Sequence 28, US/12671898
Publication No. US20100297168A1
GENERAL INFORMATION
APPLICANT: INSTITUT PASTEUR
TITLE OF INVENTION: LENTIVIRAL GENE TRANSFER VECTORS SUITABLE FOR ITERATIVE
TITLE OF INVENTION: ADMINISTRATION
FILE REFERENCE: B07146A -AD/CAL
CURRENT APPLICATION NUMBER: US/12/671,898
CURRENT FILING DATE: 2010-02-02
PRIOR APPLICATION NUMBER: PCT/IB2008/002930
PRIOR FILING DATE: 2008-08-01
PRIOR APPLICATION NUMBER: EP 07290979.9
PRIOR FILING DATE: 2007-08-03
PRIOR APPLICATION NUMBER: EP 07291251.2
PRIOR FILING DATE: 2007-10-12
PRIOR APPLICATION NUMBER: EP 08156405.6
PRIOR FILING DATE: 2008-05-16
PRIOR APPLICATION NUMBER: EP 07290980.7
PRIOR FILING DATE: 2007-08-03
NUMBER OF SEQ ID NOS: 84
SEQ ID NO 28
LENGTH: 509
TYPE: PRT
ORGANISM: Vesicular stomatitis virus
Query Match 96.0%; Score 2589; Length 509;
Best Local Similarity 94.9%;
Matches 466; Conservative 12; Mismatches 13; Indels 0; Gaps 0;
Qy 1 IPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICH 60
||||||||:|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 IPIFVPSGQNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICH 78
Qy 61 AAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVT 120
||||||||||||||||||||||||||||||||:||| |||||||||||||||||||||||
Db 79 AAEWKTTCDYRWYGPQYITHSIHPISPTIDECKRIISRIASGTDEDLGFPPQSCGWASVT 138
Qy 121 TVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKH 180
|||||||:|||||||||||||||||||||||||||||||||||||||||:||||||| ||
Db 139 TVSNTNYKVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITDETVQHECEKH 198
Qy 181 IEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTA 240
||||||||||| |||| :| ||||||:|||||||||||:||||||||||| |||||||||
Db 199 IEEVEGIMYGNAPRGDAIYINNFIIDKHHRVYRFGGSCRMKFCNKDGIKFTRGDWVEKTA 258
Qy 241 GTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSV 300
||| |: |:|:| |||||||||||||||||||||||||||||||||||||| |||||||
Db 259 ETLTNIYANIPECADGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINNQEKLTSV 318
Qy 301 DLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSLNGTDPRTNASRVFWDDW 360
|||||||||||||||||||||||||||||||:||||||||||||||||||||||||||||
Db 319 DLSYLAPRIGGFGSVFRVRNGTLERGSTTYIKIEVEGPIVDSLNGTDPRTNASRVFWDDW 378
Qy 361 ELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 379 ELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDD 438
Qy 421 IFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKRP 480
||||||||||||||||||||||||||||||| |||||||||||||||||||||||:||||
Db 439 IFFDNTGENGNPVDAVVEWVSGWGTSLKFFGTTLVALILIFLLIRCCVACTYLMKKSKRP 498
Qy 481 ATESHEMRSLV 491
||||||||| |
Db 499 ATESHEMRSFV 509
Regarding claim 105, Charneu teaches that the G protein of SVCV can be used to pseudotype lentivirus (¶0098).
Regarding claim 106, Charneu teaches that the viral particle further comprises a heterologous nucleic acid molecule of interest (Fig. 2C, 12C).
Regarding claims 113 and 114, Taube teaches the targeting moiety is attached to the viral surface through an IgG Fc stalk (Figure 1, Figure 4, Discussion ¶6,).
Regarding claim 117, Taube teaches a method of generating viral particles by transducing 293T cells with nucleic acid encoding gag-pol, a nucleic acid encoding the polypeptide, and a nucleic acid encoding the targeting moiety to produce high titer viral particles (Section: Generation of scFvFc-TM/VSV-G pseudotyped lentiviruses and 293T cells stably expressing scFvFc-TM through lentiviral transduction).
Regarding claim 118, Taube teaches a method of contacting Hela cells with a VSV-G pseudotyped viral particles expressing a scFVFc-CD28-gp41-ZsGreen (Section: Immunofluorescence of pseudotyped viruses).
Charneu and Taube are considered to be analogous to the claim invention because they teach pseudotyped lentiviruses. Charneu teaches lentivirus can be pseudotyped with SVCV-G protein (¶0098). Taube teaches that a lentivirus can be pseudotyped with VSV-G protein as well as a targeting moiety that is attached to an IgG Fc stalk (Figure 1, Figure 4, Discussion ¶6).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to pseudotype a lentivirus with a viral structure protein that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2, as taught by Charneu, and a targeting moiety that is attached to an IgG Fc stalk, as taught by Taube, because doing so would advantageously impact viral tropism, reducing off target cell targeting while also increasing affinity for targeted cell types. Additionally, the IgG Fc stalk acts as stable base for the targeting moiety ensuring proper moiety display One of ordinary skill in the art would have had a reasonable expectation of success in pseudotyping a lentivirus with a viral structure protein that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2 and a targeting moiety that is attached to an IgG Fc stalk a fusion protein given that both methods of pseudotyping are 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 104 is rejected under 35 U.S.C. 103 as being unpatentable over Taube and Charneu as applied to claims 103, 105, 106, 113, 114, 117, and 118 above, and further in view of Kuo et al (US20100316663A1, hereinafter, “Kuo”).
As discussed above, claims 1 and 3 – 7 were rendered prima facie obvious by Taube and Charneu. While the references teach a pseudotyped lentivirus with SVCV G protein and a targeting moiety, the references fail to teach SEQ ID NO: 2.
However, Kuo teaches a subunit vaccine along with carriers and adjuvants for aquaculture (Abstract). Kuo teaches the subunit vaccine can be targeted towards SVCV G protein (¶0021, Claim 9). Kuo also teaches the sequence of the SVCV G protein (SEQ ID NO: 32).
Regarding claim 104, Kuo teaches a 99.6% identity to SEQ ID NO: 2, with one mismatch and one conservative amino acid substitution out of 491 amino acids (Reproduced below, Qy is SEQ ID NO: 2, Db is Kuo). These differences between the known sequences and those claimed in the application are patently insignificant and would reasonably constitute common genomic variations within viruses that can be due to stochastic variation and/or technical sequencing errors or artifacts. Absent unexpected results, SEQ ID NO: 2 is obvious to those found in prior art and practically insignificant.
US-12-746-409A-32
Sequence 32, US/12746409A
Publication No. US20100316663A1
GENERAL INFORMATION
APPLICANT: Schweitzer Co., Ltd.
TITLE OF INVENTION: A Subunit Vaccine for Aquaculture
FILE REFERENCE: PCT/CN2007/003438
CURRENT APPLICATION NUMBER: US/12/746,409A
CURRENT FILING DATE: 2010-08-27
NUMBER OF SEQ ID NOS: 48
SEQ ID NO 32
LENGTH: 509
TYPE: PRT
ORGANISM: Spring Viremia of Carp Virus (SVCV)
Query Match 99.6%; Score 2687; Length 509;
Best Local Similarity 99.6%;
Matches 489; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 1 IPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 IPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICH 78
Qy 61 AAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 79 AAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVT 138
Qy 121 TVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKH 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 139 TVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKH 198
Qy 181 IEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 199 IEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTA 258
Qy 241 GTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 259 GTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSV 318
Qy 301 DLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSLNGTDPRTNASRVFWDDW 360
|||||||||||||||||||||||||||||||:||||||||||||||||||||||||||||
Db 319 DLSYLAPRIGGFGSVFRVRNGTLERGSTTYIKIEVEGPIVDSLNGTDPRTNASRVFWDDW 378
Qy 361 ELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 379 ELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDD 438
Qy 421 IFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKRP 480
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |
Db 439 IFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKLP 498
Qy 481 ATESHEMRSLV 491
|||||||||||
Db 499 ATESHEMRSLV 509
Charneu, Taube, and Kuo are considered to be analogous to the claim invention because they deal with viral mechanisms. Charneu teaches lentivirus can be pseudotyped with SVCV-G protein (¶0098). Taube teaches that a lentivirus can be pseudotyped with VSV-G protein as well as a targeting moiety that is attached to an IgG Fc stalk (Figure 1, Figure 4, Discussion ¶6). Kuo teaches the sequence of SVCV G protein that is a near identical match to SEQ ID NO: 2 (see above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to pseudotype a lentivirus, as taught by Charneu, with a viral structure protein that is nearly identical to the amino acid sequence of SEQ ID NO: 2, as taught by Kuo, and a targeting moiety that is attached to a IgG Fc stalk, as taught by Taube, because doing so would impact viral tropism. One of ordinary skill in the art would have had a reasonable expectation of success in pseudotyping a lentivirus with a viral structure protein that is practically identical to the amino acid sequence of SEQ ID NO: 2 and a targeting moiety that is attached to a IgG Fc stalk a fusion protein given that both methods of pseudotyping are 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.
Claims 107 – 110 are rejected under 35 U.S.C. 103 as being unpatentable over Taube and Charneu as applied to claims 103, 105, 106, 113, 114, 117, and 118 above, and further in view of Chaudhary (US20190112380A1, hereinafter, “Chaudhary”).
As discussed above, claims 103, 105, 106, 113, 114, 117, and 118 were rendered prima facie obvious by Taube and Charneu. While the references teach a pseudotyped lentivirus with SVCV G protein and a targeting moiety, the references fail to teach a viral payload encoding chimeric antigen receptors.
However, Chaudhary teaches lentivirus encoding chimeric antigen receptors (Abstract, ¶0086). Chaudhary teaches that T-cells can be engineered to express chimeric antigen receptors (CARs) to target tumors for cancer immunotherapy (¶0005). Chaudhary also teaches that the use of lentivirus can lead to long-term gene transfer and can transduce hepatocytes (¶0446).
Regarding claim 107 – 110, Chaudhary teaches a lentivirus can encode a viral genome comprised of CARs and specifically teaches the amino acid sequence of a CAR with 100% identity to SEQ ID NO: 52 (reproduced below, Qy is SEQ ID NO: 52, Db is Chaudhary).
RESULT 1
US-16-089-106-2366
(NOTE: this sequence has 19 duplicates in the database searched)
Sequence 2366, US/16089106
Publication No. US20190112380A1
GENERAL INFORMATION
APPLICANT: UNIVERSITY OF SOUTHERN CALIFORNIA
APPLICANT: Chaudhary, Preet M.
TITLE OF INVENTION: CHIMERIC ANTIGEN RECEPTORS TARGETING CANCER
FILE REFERENCE: 065715-000070WO00
CURRENT APPLICATION NUMBER: US/16/089,106
CURRENT FILING DATE: 2018-09-27
PRIOR APPLICATION NUMBER: 62/314,864
PRIOR FILING DATE: 2016-03-29
NUMBER OF SEQ ID NOS: 3545
SEQ ID NO 2366
LENGTH: 244
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Polypeptide
Query Match 100.0%; Score 1287; Length 244;
Best Local Similarity 100.0%;
Matches 244; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIKGGGGSGGGGSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIKGGGGSGGGGSGGG 120
Qy 121 GSEVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSEVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSI 180
Qy 181 GYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTV 240
Qy 241 TVSS 244
||||
Db 241 TVSS 244
Charneu, Taube, and Chaudhary are considered to be analogous to the claim invention because they deal with pseudotyped lentiviral mechanisms. Charneu teaches lentivirus can be pseudotyped with SVCV-G protein (¶0098). Taube teaches that a lentivirus can be pseudotyped with VSV-G protein as well as a targeting moiety that is attached to an IgG Fc stalk (Figure 1, Figure 4, Discussion ¶6). Chaudhary teaches a lentivirus can encode a viral genome comprised of CARs and specifically teaches the amino acid sequence of a CAR with 100% identity to SEQ ID NO: 52 (see above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to pseudotype a lentivirus with a viral structure protein that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2, as taught by Charneu, and a targeting moiety that is attached to a IgG Fc stalk, as taught by Taube, encoding a CAR with 100% identity to SEQ ID NO: 52 because doing so would direct viral transduction of CARs for the targeting of cancer cells. One of ordinary skill in the art would have had a reasonable expectation of success in using pseudotyped lentivirus encoding a CAR with 100% identity to SEQ ID NO: 52 given that this combination of cancer immunotherapy 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.
Claims 111, 112, and 115 are rejected under 35 U.S.C. 103 as being unpatentable over Taube and Charneu as applied to claims 103, 105, 106, 113, 114, 117, and 118 above, and further in view of Najjar (US20230167158A1, hereinafter, “Najjar”).
As discussed above, claims 103, 105, 106, 113, 114, 117, and 118 were rendered prima facie obvious by Taube and Charneu. While the references teach a pseudotyped lentivirus with SVCV G protein and a targeting moiety, the references fail to teach a directed targeting of CD7+ T-cells.
However, Najjar teaches a fusion protein comprising a VSV-G protein, fragment, or analog thereof linked to a polypeptide with an antigen binding domain specific to CD3 that are configure to express CAR in T-cells (Title, Abstract). Najjar also teaches that this fusion protein can be used to pseudotype lentivirus (Claim 20). Furthermore, Najjar teaches that this method retargeting pseudotyped lentiviruses can be used to target other CD expressing cells (Claim 20, ¶0149).
Regarding claims 111, 112, and 115, Najjar teaches that the pseudotyped lentivirus can be comprised of a VSV-G protein and a targeting moiety for CD7 that be used to target T-cells (Claim 20, ¶0070, 0149).
Charneu, Taube, and Najjar are considered to be analogous to the claim invention because they deal with pseudotyped lentiviral mechanisms. Charneu teaches lentivirus can be pseudotyped with SVCV-G protein (¶0098). Taube teaches that a lentivirus can be pseudotyped with VSV-G protein as well as a targeting moiety that is attached to an IgG Fc stalk (Figure 1, Figure 4, Discussion ¶6). Najjar teaches that the pseudotyped lentivirus can be comprised of a VSV-G protein and a targeting moiety for CD7 that be used to target T-cells (Claim 20, ¶0070, 0149).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to pseudotype a lentivirus with a viral structure protein that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2, as taught by Charneu, and a targeting moiety that binds to CD7+ T-cells, as taught by Najjar, because doing so would direct viral transduction of CARs to CD7+ cells while reducing binding to cells expressing SVCV native cellular target receptors (¶0070). One of ordinary skill in the art would have had a reasonable expectation of success in using pseudotyped lentivirus with both a viral structure protein that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2 and a targeting moiety that binds to CD7 given that this method of increasing targeting towards desired cell types along with the reduction of off-target infection 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.
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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