DETAILED ACTION
Claims 1, 12, 20, 23, 34, 38, and 42-52 are pending and under examination in this application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 9/19/24 (2) are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statements have been considered by the examiner and initialed and signed copies of the 1449s are attached to this action.
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 12 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 12 recites the limitation where the human portion of the chimeric polypeptide “comprises at least the domains of human CD4 polypeptide as set forth in FIG. 1”. As set forth in MPEP 2173.05(s):
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)
The domains of a human CD4 polypeptide can be set forth in words and do not qualify as an “exceptional circumstance”. Further, it is not clear which elements depicted in Figure 1 qualify as a polypeptide “domain”. Figure 1 depicts a nucleotide acid structure with human CD4 and mouse CD4 exons, not polypeptide domains. There is one notation for in exon 8 for “TM”. This is undefined, but assuming this is for “transmembrane”, this is the only indication for a “domain”. However, this is a mouse exon, not a human exon. Thus, as Figure 1 does not actually depict a chimeric CD4 polypeptide, or identify one or more human CD4 domains thereof, the metes and bounds of “at least the domains of human CD4 polypeptide as set forth in FIG. 1” cannot be determined.
In the interests of compact prosecution, claim 12 as been given its broadest reasonable interpretation of encompassing a chimeric CD4 polypeptide with at least one human domain.
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.
Claims 1, 12, 20, 23, 31, 34, and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Application Publication 2005/0066375 (2005), hereafter referred to as Thiam et al.
Thiam et al. teaches a HLA multi-transgenic mouse model in which a chimeric gene is introduced into the corresponding CD4 and CD8 murine locus by targeted insertion where the chimeric gene encodes all or part of the extracellular part of the human CD4 or CD8 molecule and the transmembrane and intracellular part of the murine molecules such that the MHC/CD4 or CD8 recognition in such an animal model is human, while the transduction of the signal within the T lymphocyte is murine (Thiam et al., paragraphs 10, 61, and 63). Thiam et al. teaches that the goal is to provide humanized HLA multi–transgenic animal models for all molecules playing a key role in the initiation of an immune response, while preserving signaling in the murine T lymphocytes (Thiam et al., paragraph 11). Thiam et al. teaches that HLA multi-transgenic mouse also comprises knock-in of all or part of a human class I HLA antigen, and a knock-in of all or part of the nucleotides sequences encoding a class II HLA molecule into the homologous animal gene(s) (Thiam, paragraphs 55-56, 64). Thiam et al. further teaches that the transgenic animal comprises a knock-in of all or part of the human beta-2 microglobulin at the homologous animal gene (Thiam et al., paragraphs 63-64). In regards to CD8, Thiam et al. further teaches that the CD8 molecule is a heterodimer comprising an alpha and beta subunit encoded by two different genes (Thiam et al., paragraph 84). Thiam et al. teaches to knock-in two chimeric genes comprising the extracellular part of the human CD8 alpha and CD8 beta respectively into the homologous mouse CD8 alpha and CD8 beta genes (Thiam et al., paragraphs 84-85). Thiam et al. teaches that knock-in inactivates the endogenous genes (Thiam et al., paragraphs 84-85). Thiam et al. also teaches that knock-in places the human or humanized genes under transcriptional control of the endogenous gene's regulatory elements (Thiam et al., paragraph 48). Note that the use of the endogenous gene's regulatory elements results in the same expression of the human or humanized genes as the replaced endogenous gene(s), i.e. no expression of CD4 or CD8 in B cells, and no expression of CD4 in T cells of the CD8 lineage and vice versa. In addition, Thiam et al. teaches animal cells comprising said genetic modifications, specifically mouse cells including T cells, and methods of testing using said cells or transgenic mice, especially the testing of antigenic recognition and cell activation by the genetically modified T cells (Thiam et al., paragraphs 68, 72,-73, 76-77). Thus, by teaching all the limitations of the claims as written, Thiam et al. anticipates the instant invention as claimed.
Claim Rejections - 35 USC § 103
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.
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 1, 12, 20, 23, 34, 38, and 49-52 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2005/0066375 (2005), hereafter referred to as Thiam et al., in view of Nakayama et al. (1992) J. Immunol., Vol. 148, 1919-1927, Nakayama et al. (1989) Immunogenetics, Vol. 30, 393-397, Vignali et al. (1999) J. Immunol., Vol. 162, 1431-1439, Moldovan et al. (2002) J. Immunol., Vol. 169, 6261-6268, and U.S. Patent 5,958,678 (1999), hereafter referred to as Maddon et al.
It is noted that certain claims recite the inclusion of specific amino acid sequences as set forth in specific SEQ ID NOS. However, the claims recite polypeptides which comprise “an amino acid sequence set forth in SEQ ID NO….”, or “an amino acid sequence set forth as SEQ ID NO…”. The use of the phrase “an amino acid sequence” does not limit the claim to the entire sequence referenced, but rather encompasses any sequence that contains any amino acid sequence present in the recited SEQ ID NO. If applicant which to claim a specific sequence in its entirety, it is suggested that applicant amend the claims to recite, "..comprises the amino acid sequence set forth in/as SEQ ID NO ...". However, as currently written, the claims have been given their broadest reasonable interpretation as examined as comprising an amino acid sequence present in one of the recited SEQ ID NOS but not limited to the entire sequence as set forth in each SEQ ID NO.
Thiam et al. teaches a HLA multi-transgenic mouse model in which a chimeric gene is introduced into the corresponding CD4 and CD8 murine locus by targeted insertion where the chimeric gene encodes all or part of the extracellular part of the human CD4 or CD8 molecule and the transmembrane and intracellular part of the murine molecules such that the MHC/CD4 or CD8 recognition in such an animal model is human, while the transduction of the signal within the T lymphocyte is murine (Thiam et al., paragraphs 10, 61, and 63). Thiam et al. teaches that the goal is to provide humanized HLA multi–transgenic animal models for all molecules playing a key role in the initiation of an immune response, while preserving signaling in the murine T lymphocytes (Thiam et al., paragraph 11). Thiam et al. teaches that HLA multi-transgenic mouse also comprises knock-in of all or part of a human class I HLA antigen, and a knock-in of all or part of the nucleotides sequences encoding a class II HLA molecule into the homologous animal gene(s) (Thiam, paragraphs 55-56, 64). Thiam et al. further teaches that the transgenic animal comprises a knock-in of all or part of the human beta-2 microglobulin at the homologous animal gene (Thiam et al., paragraphs 63-64). In regards to CD8, Thiam et al. further teaches that the CD8 molecule is a heterodimer comprising an alpha and beta subunit encoded by two different genes (Thiam et al., paragraph 84). Thiam et al. teaches to knock-in two chimeric genes comprising the extracellular part of the human CD8 alpha and CD8 beta respectively into the homologous mouse CD8 alpha and CD8 beta genes (Thiam et al., paragraphs 84-85). Thiam et al. teaches that knock-in inactivates the endogenous genes (Thiam et al., paragraphs 84-85). Thiam et al. also teaches that knock-in places the human or humanized genes under transcriptional control of the endogenous gene's regulatory elements (Thiam et al., paragraph 48). Note that the use of the endogenous gene's regulatory elements results in the same expression of the human or humanized genes as the replaced endogenous gene(s), i.e. no expression of CD4 or CD8 in B cells, and no expression of CD4 in T cells of the CD8 lineage and vice versa. In addition, Thiam et al. teaches animal cells comprising said genetic modifications, specifically mouse cells including T cells, and methods of testing using said cells or transgenic mice, especially the testing of antigenic recognition and cell activation by the genetically modified T cells (Thiam et al., paragraphs 68, 72,-73, 76-77).
While Thiam et al. teaches to knock-in two chimeric genes comprising the extracellular part of the human CD8 alpha and CD8 beta respectively into the homologous mouse CD8 alpha and CD8 beta genes, Thiam et al. does not specifically teach the nucleotide or amino acid sequence of the extracellular portions of human CD8 alpha and human CD8 beta. However, the nucleotide and amino acid sequences for human CD8 alpha and human CD8 beta were well known at the time of filing, including amino acid sequence for the human CD8 alpha and human CD8 beta extracellular domains which is 100% identical to sequence present in SEQ ID NOS 59 and 58 respectively. Nakayama et al. (1992), for example, teaches an amino acid sequence of human CD8 beta comprising sequence which is 100% identical to SEQ ID NO:58, and clearly identifies the extracellular portions of the molecule (Nakayama et al., Figures 1 and 5). Nakayama et al. (1989), for example, teaches an amino acid sequence of human CD8 alpha which comprises sequence 100% identical to SEQ ID NO:59, and clearly identifies the extracellular portions of the molecule (Nakayama et al., Figures 1 and 2). Note as well that that the sequences for the extracellular portions of human CD8 alpha and beta taught by Nakayama 1989 and 1992 are also present in SEQ ID NOS 53 and 54. Nakayama 1989 and 1992 also provides the exon/intron structure of molecules such that the sequence of the extracellular portion of the CD8 alpha and beta can be mapped to the genomic sequence to identify the human exons required to replace these sequences in corresponding mouse loci. Thus, based on the well known sequences of the extracellular portions of human CD8 alpha and beta as evidenced by both Nakayama references and the well known human exon/intron structure of both chains, it would have prima facie obvious to the skilled artisan at the time of filing to make the transgenic animals taught by Thiam et al. where the human genomic sequence used to replace the mouse genomic sequence corresponds to the sequences for the human CD8 alpha and beta extracellular domains taught by the Nakayama references in order to produce chimeric CD8 alpha and CD8 beta nucleotide sequences encoding chimeric CD8 alpha and CD8 beta polypeptides as claimed with a reasonable expectation of success.
Further, while Thiam et al. teaches to knock-in sequence encoding the extracellular domain of human CD4 into the endogenous mouse CD4 gene, Thiam et al. does not specifically teach to knock in only the D1-D3 domains of human CD4 such that the resulting modified gene expresses a chimeric CD4 comprising human D1-D3 domains and mouse D4, transmembrane and cytoplasmic domains. However, Thiam et al. does teach that the CD4 molecule combines with the TCR-MHC-peptide complex and that this association does not take place between xenogenic molecules under satisfactory conditions, as demonstrated in earlier models of transgenic mice reported in the art, and that this is why the invention relates to an HLA multi-transgenic mouse model in which a chimeric CD4 molecule is expressed such that MHC/CD4 recognition in the mouse is human while the transduction of the signal within the T lymphocyte is murine (Thiam et la., paragraph 10). At the time of filing, the structure of the extracellular domain was well known to include four domains, D1-D4. Of these, Vignoli et al. teaches that D1-D3 are all important in direct binding to MHC and TCR (Vignoli et al. page 1431). The D4 domain, on the other hand, does not participate in MHC or TCR binding and instead is important for CD4 dimerization (Moldovan et al., page 6261). It is further noted that the sequence of the extracellular domain of human CD4 comprising D1-D3 was also known in the prior art, see for example Maddon et al. who teaches the amino acid sequence comprising D1-D3 of CD4 (referred to as the V1-J1, V2-J2, and V3-J3 of T4), which is 100% identical to the sequence the human portion of SEQ ID NO:4, which is separately disclosed as SEQ ID NO:57 in the instant specification (Maddon et al., claim 1, SEQ ID NO:1). Maddon et al. also teaches a nucleic acid sequence encoding D1-D3 as set forth in SEQ ID NO:1, the structure of the genomic locus of CD4 (T4) including exons and introns, and including the location of the D1-D3 domains within the exons (Maddon et al., columns 12-16 and Figures 6 and 10). Thus, by providing the exon/intron structure of molecules, the sequence of the D1, D2, and D3 domains can be mapped to the genomic sequence to identify the human exons or portions thereof required to replace these sequences in corresponding mouse loci. Therefore, based on the teachings of Thiam et al. to insert a part of the human CD4 gene into endogenous mouse CD4 gene in a mouse and that the purpose of expressing a chimeric human/mouse CD4 molecule in a mouse comprising human MHC molecules is to ensure human MHC/CD4 recognition while retaining mouse signaling, the teachings of Vignoli et al. and Moldovan et al. that D1-D3, but not D4, are involved in MHC/TCR binding by CD4, and the known nucleic acid sequence encoding the amino acid sequence of D1-D3, including D1-D3 sequence 100% identical to sequence in SEQ ID NO:57 and SEQ ID NO:4 and the known CD4 genomic locus exon and introns, it would have been prima facie obvious to the skilled artisan at the time of filing to replace the endogenous mouse D1-D3 domains of the mouse CD4 locus with genomic DNA exon sequence encoding only the D1-D3 domains of human CD4 into the endogenous mouse CD4 gene such that the modified chimeric nucleic acid at the endogenous CD4 locus expresses a chimeric CD4 comprising the D1-D3 domains of human CD4 as set forth in SEQ ID NO:4 and the D4, transmembrane, and cytoplasmic domains of mouse CD4 such that the resulting chimeric gene a sequence set forth in SEQ ID NO:3 and encodes a sequence as set forth in SEQ ID NO:4 with a reasonable expectation of success.
Please note that any evidence and arguments presented in related applications must be resubmitted in the instant application for consideration.
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, 23, 31, 34, 38, and 49-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 9,848,587, hereafter referred to as the ‘587 patent, either alone or in view of Nakayama et al. (1992) J. Immunol., Vol. 148, 1919-1927, and Nakayama et al. (1989) Immunogenetics, Vol. 30, 393-397.
The ‘587 patent claims are a species of broader instant claims 1, 23, 31, 34, and 38. The ‘587 patent claims recite a narrower embodiment of these instant claims where genetically modified non-human animal comprises a first nucleotide sequence encoding a chimeric human/non-human CD8α polypeptide and a second nucleotide sequence encoding a chimeric human/non-human CD8β polypeptide, wherein the amino acid sequence of the human portion of the chimeric human/non-human CD8α polypeptide is set forth in SEQ ID NO:59 and is operably linked to non-human transmembrane and cytoplasmic domains of a non-human CD8α polypeptide, wherein the second nucleotide sequence comprises a nucleic acid sequence encoding a human CD8β polypeptide extracellular domain comprising at least the immunoglobulin V-like domain of the human CD8β polypeptide, wherein the nucleic acid sequence encoding the human CD8β polypeptide extracellular domain is operably linked to a nucleic acid sequence encoding transmembrane and cytoplasmic domains of an endogenous non-human CD8β polypeptide, and wherein the non-human animal expresses a chimeric human/non-human CD8 protein comprising the chimeric human/non-human CD8α and CD8β polypeptides (claim 1 of the ‘587 patent). Claim 22 of the ’587 patent recites a method of modifying the CD8α and CD8β loci in the mouse which is a species of the method of instant claim 31. Dependent claims of the ‘587 patent recites that the first and second sequences are present at the endogenous CD8α and CD8β gene loci. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, by reciting a species of the instant broader claims, the ‘587 patent claims render obvious instant claims 1, 23, 31, 34, and 38.
In regards to instant claims 49-52, it is first noted that the genetically modified mouse of the ‘587 patent claims comprises and encompasses the chimeric nucleic acid molecules of instant claims 49-51 and T cells comprising the chimeric nucleic acids. Second, the ‘587 patent claims, while not specifying the exon intron structure of the chimeric nucleic acid present at the endogenous loci limit the human portion of nucleic acid encoding the chimeric CD8α to sequence encoding SEQ ID NO:59 and the human portion of nucleic acid encoding the chimeric CD8β to sequence encoding SEQ ID NO:58, where for each of the nucleic acid sequences they further the encode the mouse CD8α and CD8β transmembrane and cytoplasmic domains respectively at the endogenous gene loci. Dependent claims of the ‘587 patent further recite that the chimeric CD8α comprise the sequence of SEQ ID NO:54 and the chimeric CD8β comprises the sequence of SEQ ID NO:53 (‘587 claim 17). The instant claims recite the same structure and amino acid sequences for the chimeric CD8α and CD8β polypeptides as recited in the ‘587 patent claims, but further define certain mouse and human exons and introns present in the nucleotide sequence. However, the exon intron structure of the chimeric human/mouse nucleic acid molecules set forth in the instant claims is encompassed by the sequence present at the modified CD8α and CD8β loci in the genetically modified mice and thus represents an obvious variants of the ’587 patent claims. It is further noted that the sequence and exon structure of the both mouse and human CD8α and CD8β were known at the time of filing, see for example Nakayama et al. (1989) page 383 and Figure 1, and Nakayama (1992) page 1920 and Figures 1 and 4. As such, the modified nucleic acid loci present in the transgenic mice set forth in the ‘587 patent claims in view of Nakayama (1989) and Nakayama (1992) both encompass and render obvious the variant nucleic acid sequences set forth in instant claims 49-52.
Claims 1, 12, 20, and 42-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,820,581, hereafter referred to as the ‘581 patent, either alone or in view of U.S. Patent 5,958,678 (1999), hereafter referred to as Maddon et al.
The ‘581 patent claims are a species of broader instant claims 1, 12, and 20. The ‘581 patent claims recite a narrower embodiment of these instant claims where genetically modified rodent comprises a nucleotide sequence encoding a chimeric human/rodent T cell CD4 co-receptor polypeptide, wherein a human portion of the human/rodent T cell CD4 co-receptor polypeptide comprises at least D1, D2 and D3 domains of a human CD4 polypeptide, wherein a rodent portion of the chimeric human/rodent T cell CD4 co-receptor polypeptide comprises at least D4, transmembrane, and cytoplasmic domains of a rodent T cell co-receptor, and wherein the rodent expresses the chimeric human/rodent T cell CD4 co-receptor polypeptide, wherein the rodent is a rat or a mouse (claim 1 of the ‘581 patent). Claim 12 of the ’581 patent recites a method of modifying the CD4 locus in the mouse which is a species of the method of instant claim 20. Dependent claims of the ‘581 patent recites that the first and second sequences are present at the endogenous CD4 gene locus. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, by reciting a species of the instant broader claims, the ‘581 patent claims render obvious instant claims 1, 12, and 20.
In regards to instant claims 42-48, it is first noted that the genetically modified mouse of the ‘581 patent claims comprises and encompasses the chimeric nucleic acid molecules of instant claims 42-46 and T cells comprising the chimeric nucleic acids of instant claims 47-48. Second, the ‘581 patent claims, while not specifying the exon intron structure of the chimeric nucleic acid present at the endogenous loci limit the human portion of nucleic acid encoding the chimeric CD4 to sequence encoding SEQ ID NO:59 and the human portion of nucleic acid encoding the chimeric CD8β to sequence encoding SEQ ID NO:57 comprising the human D1, D2, and D3 domains, and a mouse portion comprising the D4 domain, transmembrane, and cytoplasmic domains at the endogenous gene locus. Dependent claims of the ‘581 patent further recite that the chimeric CD4 comprise the sequence of SEQ ID NO:4 (‘581 claim 10). The instant claims recite the same structure and amino acid sequences for the chimeric CD4 polypeptide as recited in the ‘581 patent claims, but further define certain mouse and human exons and introns present in the nucleotide sequence. However, the exon intron structure of the chimeric human/mouse nucleic acid molecules set forth in the instant claims is encompassed by the sequence present at the modified CD4 locus in the genetically modified mice or the ‘581 patent claims and thus represents an obvious variant of the ’581 patent claims. It is further noted that the sequence and exon structure of the both mouse and human CD4 were known at the time of filing, see for example Maddon et al., SEQ ID NO:1, columns 12-16, and Figures 6 and 10. As such, the modified nucleic acid locus present in the transgenic mice set forth in the ‘581 patent claims in view of Maddon et al. both encompasses and render obvious the variant nucleic acid sequences and T cells set forth in instant claims 42-48.
Claims 1, 12, 20, 23, 31, 34, 38, and 42-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,259,510, hereafter referred to as the ’510 patent, either alone or in view of Nakayama et al. (1992) J. Immunol., Vol. 148, 1919-1927, and Nakayama et al. (1989) Immunogenetics, Vol. 30, 393-397, and U.S. Patent 5,958,678 (1999), hereafter referred to as Maddon et al.
The ‘510 patent claims are a species of broader instant claims 1, 12, 20, 23, 31, 34, and 38. The ‘510 patent claims recite a narrower embodiment of these instant claims where genetically modified mouse c A genetically modified mouse comprising in its genome (a) a first nucleotide sequence encoding a chimeric human/mouse CD4 co-receptor that comprises D1, D2 and D3 domains of a human CD4 polypeptide and transmembrane and cytoplasmic domains of a mouse CD4 polypeptide; (b) a second nucleotide sequence encoding a chimeric human/mouse CD8α polypeptide and a third nucleotide sequence encoding a chimeric human/mouse CD8β polypeptide, wherein the chimeric human/mouse CD8α polypeptide comprises an IgV-like domain of a human CD8α polypeptide and transmembrane and cytoplasmic domains of a mouse CD8α polypeptide, wherein the chimeric human/mouse CD8β polypeptide comprises an IgV-like domain of a human CD8β polypeptide and transmembrane and cytoplasmic domains of a mouse CD8β polypeptide, wherein the mouse comprises further heterologous sequences and, wherein the mouse expresses a chimeric human/non-human CD4 protein, and CD8 protein comprising the chimeric human/non-human CD8α and CD8β polypeptides (claim 1 of the ‘510 patent). Claim 20 of the ’510 patent recites a method of modifying the CD4, CD8α, and CD8β loci in the mouse which is a species of the method of instant claim 31. Claim 23 of the ‘510 patent recites method of obtaining a T cell from the genetically modified mouse. Dependent claims of the ‘510 patent recites that the first and second sequences are present at the endogenous CD4, CD8α, and CD8β gene loci. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, by reciting a species of the instant broader claims, the ‘510 patent claims render obvious instant claims 1, 12, 20, 23, 31, 34, and 38.
In regards to instant claims 42-52, it is first noted that the genetically modified mouse of the ‘510 patent claims comprises and encompasses the chimeric nucleic acid molecules of instant claims and T cells comprising the chimeric nucleic acids or instant claims 42-52. Second, the ‘510 patent claims, while not specifying the exon intron structure of the chimeric nucleic acid present at the endogenous loci does limit the human portion of nucleic acid encoding the chimeric CD4, CD8α, and CD8β to particular human sequence to particular human extracellular domains, and where for each of the nucleic acid sequences the human sequence is linked to mouse CD8α and CD8β transmembrane and cytoplasmic domains respectively at the endogenous gene loci. In particular, note that the human portion of the chimeric CD4 comprises the D1, D2, and D3 domains of human CD4 and the mouse portion comprises D4, transmembrane, and cytoplasmic domains of the mouse CD4 molecule, and the human portion of the chimeric CD8α and CD8β comprises the human IgV like domains and the mouse portion comprises the mouse CD8 transmembrane and cytoplasmic domains (‘510 claims 1 and 5). The instant claims recite the same structure and amino acid components for the chimeric CD4, CD8α, and CD8β polypeptides as recited in the ‘510 patent claims, but further define certain mouse and human exons and introns present in the nucleotide sequence. However, the exon intron structure of the chimeric human/mouse nucleic acid molecules set forth in the instant claims is encompassed by the sequence present at the modified CD4, CD8α, and CD8β loci in the genetically modified mice and thus represents an obvious variants of the ’510 patent claims. It is further noted that the sequence and exon structure of the both mouse and human CD8α and CD8β were known at the time of filing, see for example Nakayama et al. (1989) page 383 and Figure 1, and Nakayama (1992) page 1920 and Figures 1 and 4. Likewise, the sequence and exon structure of the both mouse and human CD4 were known at the time of filing, see for example Maddon et al., SEQ ID NO:1, columns 12-16, and Figures 6 and 10. As such, the modified nucleic acid loci present in the transgenic mice set forth in the ‘510 patent claims in view of Nakayama (1989), Nakayama (1992), and Maddon et al. both encompass and render obvious the variant nucleic acid sequences and T cells set forth in instant claims 42-52.
Claims 49-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-16, and 18-23 of U.S. Patent No. 12,063,915, hereafter referred to as the ‘915 patent, in view of Nakayama et al. (1992) J. Immunol., Vol. 148, 1919-1927, and Nakayama et al. (1989) Immunogenetics, Vol. 30, 393-397.
The ‘915 patent claims are drawn to genetically modified rodent cells which are T cells which comprise (i) a first nucleotide sequence encoding a chimeric human/rodent CD8α polypeptide, wherein the amino acid sequence of the human portion of the chimeric human/rodent CD8α polypeptide (a) is the amino acid sequence set forth in SEQ ID NO:59 and (b) is operably linked to transmembrane and cytoplasmic domains of a rodent CD8α polypeptide, and (ii) a second nucleotide sequence encoding a chimeric human/rodent CD8β polypeptide, wherein the amino acid sequence of the human portion of the chimeric human/rodent CD8β polypeptide (a) comprises at least an immunoglobulin V-like domain of a human CD8β polypeptide and (b) is; operably linked to a nucleic acid sequence encoding transmembrane and cytoplasmic domains of rodent CD8β polypeptide. the ‘915 patent claims, while not specifying the exon intron structure of the chimeric nucleic acid present at the endogenous loci limit the human portion of nucleic acid encoding the chimeric CD8α to sequence encoding SEQ ID NO:59 and the human portion of nucleic acid encoding the chimeric CD8β to sequence encoding SEQ ID NO:58, where for each of the nucleic acid sequences they further the encode the mouse CD8α and CD8β transmembrane and cytoplasmic domains respectively at the endogenous gene loci (‘915 patent claims 13, 20, and 21). Dependent claims of the ‘915 patent further recite that the chimeric CD8α comprise the sequence of SEQ ID NO:54 and the chimeric CD8β comprises the sequence of SEQ ID NO:53 (‘915 claim 22). The instant claims recite the same structure and amino acid sequences for the chimeric CD8α and CD8β polypeptides as recited in the ‘915 patent claims, but further define certain mouse and human exons and introns present in the nucleotide sequence. However, the exon intron structure of the chimeric human/mouse nucleic acid molecules set forth in the instant claims is encompassed by the sequence present at the modified CD8α and CD8β loci in the genetically modified T cells and thus represents an obvious variants of the ’915 patent claims. It is further noted that the sequence and exon structure of the both mouse and human CD8α and CD8β were known at the time of filing, see for example Nakayama et al. (1989) page 383 and Figure 1, and Nakayama (1992) page 1920 and Figures 1 and 4. As such, the modified nucleic acid loci present in the genetically modified T cells set forth in the ‘915 patent claims in view of Nakayama (1989) and Nakayama (1992) both encompass and render obvious the variant nucleic acid sequences and T cells set forth in instant claims 49-52.
No claims are allowed.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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