DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ amendments to the claims and arguments filed on August 7, 2026, have been received and entered. Claims 8, 10, 11, 19-20 and 21 have been amended, while claims 7, 9, 18 and 20 have been canceled.
Claims 1-6, 8, 10-17, 19-20 and 21 are pending in the instant application.
Election/Restrictions
Applicants’ election without traverse of claims 7-11 (group II) in the reply filed on February 12, 2026, is acknowledged. Applicants’ election of YLR3 intracellular domain species of TLR intracellular domain cancer antigen as species of the target factor and cancer as specie of target disease in the reply filed on February 12, 2026, is also acknowledged. Upon further consideration, election of species requirement is hereby withdrawn, and all the non-elected species are rejoined with the elected invention.
Claims 1-6, 12-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 12, 2026.
Priority
This application is 371 of PCT/JP2021/043978 filed on11/30/2021, which claims priority from foreign application JP 2021-005337 filed on 01/15/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicants cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/23/026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claims 8, 10-11, 19-20 and 21 are under consideration.
Withdrawn-Claim Rejections - 35 USC § 102
Claims 7-11, 20-21 and 22 were rejected under 35 U.S.C. 102 (a)(1) /102(a) (2) as being anticipated by Shen et al (WO2020/210816, dated 10/15/2020, EFD, 4/12/2019). In view of Applicants’ amendment of base claim, introducing the limitation “TLR intracellular domain is TLR2, TLR3 or TLR9, the previous rejections of claims are hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are, however, subject to new rejections over the prior art of record, as set forth below.
Claims 7-8, 11, 18 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Corey et al (WO2019067328, dated 04/04/2019). In view of Applicants’ amendment of base claim, introducing the limitation “TLR intracellular domain is TLR2, TLR3 or LLR9” and target factor binding factor limiting to cancer antigen, the previous rejections of claims are hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are, however, subject to new rejections over the prior art of record, as set forth below.
New-Claim Rejections - 35 USC § 102 -necessitated by amendments
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8, 10-11, 19-20 and 21 are rejected under 35 U.S.C. 102(a) (2) as being anticipated by Gill et al (US20220119476, dated 04/21/20222, filed on 8/30/2019, EFD4/3/2019).
With respect to claims 8, 10, 19, 21, Gill teaches a dendritic cell expressing a chimeric antigen receptor (abstract para. 7) comprising a nucleic acid encoding antigen binding domain, a transmembrane domain and an intracellular domain (see para. 11), wherein the transmembrane domain selected from group consisting of CD28, CD3 epsilon, CD45, CD4 (see para. 168), wherein the intracellular domain selected from group consisting of TLR2, TLR3 and TLR9 (see para. 173-174), wherein the targeting factor binding domain is a cancer antigen is an scFV or human antibody selected from the group consisting of CD19 and Her2 (see para. 161-163, 65).
Regarding claim 10, Gill teaches a pharmaceutical composition comprising the APC comprising exogenous nucleic acid molecule encoding a chimeric antigen receptor (CAR) as discussed above that exhibits an increase in the antigen presenting ability of the cell intended for therapeutic (see abstract para. 16, 254).
With respect to claim 20, Gill further teaches that the intracellular domain may include one or more of molecules selected from TLR2, 3, 9 and CD40 (see para. 173).
Accordingly, Gill anticipates claims 8, 10-11, 19-20 and 21.
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 8, 10-11, 19-20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Gill et al (US20220119476, dated 04/21/20222,) and Lai et al (Leukemia (2018) 32, 801–808) and Wagner (WO2020243334, dated 12/3/2020, EFD05/29/2019).
With respect to claims 8, 10, 19, 21, Gill teaches a dendritic cell expressing a chimeric antigen receptor (abstract para. 7) comprising a nucleic acid encoding antigen binding domain, a transmembrane domain and an intracellular domain (see para. 11), wherein the transmembrane domain selected from group consisting of CD28, CD3 epsilon, CD45, CD4 (see para. 168), wherein the intracellular domain selected from group consisting of TLR2, TLR3 and TLR9 (see para. 173-174), wherein the targeting factor binding domain is a cancer antigen is an scFV or human antibody selected from the group consisting of CD19 and Her2 (see para. 161-163, 65).
Regarding claim 10, Gill teaches a pharmaceutical composition comprising the APC comprising exogenous nucleic acid molecule encoding a chimeric antigen receptor (CAR) as discussed above that exhibits an increase in the antigen presenting ability of the cell intended for therapeutic (see abstract para. 16, 254).
With respect to claim 20, Gill further teaches that the intracellular domain may include one or more of molecules selected from TLR2, 3, 9 and CD40 (see para. 173). Gill differs from claimed invention by not explicitly disclosing proof of concept for using TLR9 intracellular domain..
Lai teaches a chimeric antigen receptor (CAR) comprising an FMC63 single-chain variable fragment (scFv) as the antigen-binding domain, a CD28 transmembrane domain, and a TLR2 as the intracellular signaling domain. Lai further teaches the use of the said CAR construct in the treatment of leukemia (see 802, col. 1, para. 2 and con 2, last para.). Wagner teaches A monocytic cell (APC) comprising a chimeric receptor expressed on its surface, the chimeric receptor comprising a target binding domain, a transmembrane domain, and an intracellular domain, wherein the cell is a dendritic cell, wherein the target binding domain of the chimeric receptor comprises an scFv and wherein the intracellular signaling domain comprises an intracellular domain of a toll-like receptor 4 (TLR) or TLR9 (see claim 43-44, , 55-56 and para 19, 63).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of Gill and Lai to modify the APC comprising the nucleic acid encoding CAR disclosed in Gill by using intracellular domain of TLR2 as suggested in Lai, to successfully study the anti-cancer effect of the APC, as instantly claimed, with a reasonable expectation of success, before the effective filing date of instant application. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art reported while TLR intracellular domain response may vary depending on the intracellular TLR domain utilized for a given chimeric receptor, it is desirable to use the signaling domain of a TLR that results in the expression of Ml- type (i.e., pro-inflammatory) cytokines, such as IL-12, IFN-a, IRN-g, TNF-a, IL-6, and/or IL-Ib because expression and activation of the disclosed chimeric receptors by APCs, allows the chimeric receptor-expressing cells to overcome the immune suppressive environment fostered by most tumors without directly attacking or phagocytosing the tumor cells like a convention CAR T-cell (see para. 39). One of skill in the art would have been expected to have a reasonable expectation of success because prior art successfully reported using TLR as intracellular domain in the CAR as evidenced by the teaching of Wagner. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396).
Claim Rejections - 35 USC § 112-written description
Claims 8, 10-11, 19-20 and 21 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.
MPEP 2163 states “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 (see i)(A) above), reduction to drawings (see i)(B) above), 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 i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). "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) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
The claims embrace any antigen presenting cell comprising a polynucleotide encoding a chimeric target factor receptor comprising a target factor-binding domain comprising a heavy-chain variable region and/or a light- chain variable region, wherein the target factor is selected from the group consisting of CD19, GD2, GD3, CD20, CD37, CEA, HER2, EGFR, type III mutant EGFR, CD38, BCMA, MUC-1, PSMA, WT1, cancer testis antigens (e.g., NY-ESO-1, and MAGE-A4), mutation peptides (e.g., k-ras, h-ras, and p53), hTERT, PRAME, TYRP1, mesothelin, PMEL, mucin, IL-4R, IL-6R, CTLA4, PSCA, Claudin 18.2, EpCAM, VEGFR2, Nectin4/FAP, LewisY, Glypican-3, IL- 13Ra2, MUC16, AXL, CD80/86, c-MET, DLL-3, DR5, EpHA2, FR-a and LMP1, a transmembrane domain selected from the group consisting of transmembrane regions of CD28, CD36, CD8a, CD3, CD4 and CD4-1BB, and an intracellular domain containing a TLR intracellular domain, wherein the TLR intracellular domain is at least one selected from the group consisting of a TLR2 intracellular domain, a TLR3 intracellular domain, and a TLR9 intracellular domain.. Thus, the claims encompass function of receptor is to bind specifically to a genus of cancer antigen set forth in claims. Dependent claim limits the target factor binding domain having any single chain antibody structure. Claims are also directed to genus of APCs comprising the polynucleotide of the invention subsequently limiting to a dendritic cells.
The specification contemplates to provide a chimeric target factor receptor capable of activating antigen- presenting cells, such as dendritic cells, in a target-factor- specific manner (see para. 6 of the specification). The specification contemplates target factors include cancer antigens, various receptors (e.g., cytokine receptors such as interleukin receptors, and cell growth factor receptors), cell adhesion factors, and membrane proteins of bacteria or viruses. Specific examples of target factors include CD19, GD2, GD3, CD20, CD37, CEA, HER2, EGFR, type III mutant EGFR, CD38, BCMA, MUC-l, PSMA, WTl, cancer testis antigens (e.g., NY-ESO-1, and MAGE-A4), mutation peptides (e.g., k-ras, h- ras, and p53), hTERT, PRAM, TYRP1, mesothelin, PMEL, mucin, IL- 12R, IL-4R, IL-13R, IL-6R, IL-23R, CTLA4, EGFR806, PSCA, Claudin, EpCAM, VEGFR2, Nectin4/FAP, LewisY, Glypican-3, IL-13Ra2, CD171, MUC16, AFP, AXL, CD80/86, c-MET, DLL-3, DR5, EpHA2, FR-a, gp100, MAGE-A1/3/4, and LMP1. The specification contemplates a domain containing one or more CDRs of an antibody or T-cell receptor typically has one or more, preferably two, three, four, five or more, more preferably all six of the CDRs of the antibody or T-cell receptor against a target factor (e.g., if the CDRs of an antibody are the case, heavy-chain CDR1, heavy-chain CDR2, heavy-chain CDR3, light-chain CDR1, light-chain CDR2, and light-chain CDR3) (see para. 36). The specification exemplifies a nucleic acid encoding a chimeric target factor receptor construct containing the following disposed in this order from the N-terminus to C-terminus comprises signal peptide of SEQ ID NO: 19 or 20, anti-Her2 scFv domain of SEQ ID NO: 1 or 9, CD29 transmembrane domain of SEQ ID NO:2 or 10 and intracellular domain as set forth in SEQ ID NO: 3, 4, , 5, 6 or 7 and further comprising CD40. The specification further teaches a chimeric target factor receptor construct containing a nucleic acid encoding signal sequence of SEQ ID NO: 19, anti-mesothelin scFV as set forth in SEQ ID NO: 17, CD 28 transmembrane domain and TLR1 to TLR9 intracellular domain. Example 2 and 3 teaches dendritic or macrophage cell expressing the chimeric target factor receptor as discussed above. The results indicate that the use of the intracellular domain of TLR for the intracellular domain can increase the expression of MHC class I and MHC class II in response to the target factor. In particular, the degree of activation was found to be high when TLR2, TLR3, or TLR9 was used (Fig. 9).
The state of the prior art summarized by the reference of Fujiwara et al (BBRC, 2020, 527, 2, 350-357) reported that the scFv structure affects CAR expression efficiency and stability on T cells and not all scFvs can be expressed as a chimeric antigen receptor (CAR) on T cells (see highlight and page 368). The teaching of Fujiwara shows that not all target factor binding domain would work due to lack of predictability across claimed genus. Xu et al (Mol Immunol. 2020 Oct:126:56-64 ) reported that CAR activity impacted by ligand-binding domain, compared to other construct components (abstract). It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of a given antibody. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain the required conformation of the CDRs are required in order to produce a protein having antigen-binding function; and further, that proper association of heavy and light chain variable regions is required in order to form functional binding sites. Rudikoff et al (Proc Natl Acad Sci USA 1982 Vol 79 page 1979-1983) teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Hasegawa (MAbs, 2017 Apr 5;9(5):854-873) supports the assertion of Rudikoff stating "Single amino acid substitution within the complementarity-determining region (CDR) and framework region can have dramatic effects Hasegawa continue to teach "examples of harmful single amino acid substitution that affect the specificity and the affinity of antigen binding are well documented. Another class of deleterious amino acid substitutions increases aggregation propensity of immunoglobulin proteins by affecting folding stability. Other disadvantageous amino acid substitution are known to impair the secretion of immunoglobulins" (see page 854, col. 2, para. 2 and references therein). A skilled artisan cannot fully describe genus, visualize or recognize the identity of the members of the genus that exhibit the structural and functional properties of the claims. There is insufficient guidance and direction as to the written description of the claimed target factor receptor comprising any cancer antigens-binding domain or cytokine receptors-binding domain or cell growth factor receptors-binding domain and any transmembrane domain in any host cell as broadly encompassed by the claimed invention.
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al (Biochemical and Biophysical Research Communications Vol. 307, pp 198-205, 2003) which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (See entire document). Casset et al also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.). Vajdos et al (Journal of Molecular Biology Vol. 320, pp 415-428, 2002) state that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen (page 416, left column). Wu et al (Journal of Molecular Biology Vol. 294, pp 151-162, 1999) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity dues in part to large conformational change in antibodies that accompany antigen binding (page 152, left column) but certain residues have been identified as important for maintaining conformation.
In the instant case, the specification lacks written description for making and using a functional polynucleotide encoding a genus of chimeric target factor receptor comprising any target factor-binding domain, any transmembrane domain, and an intracellular domain containing any TLR intracellular domain in any host cells as broadly encompassed by claims 7 and 8. As stated before, claims encompass a broad genus of target factor binding domain in any host cell . The guidance provided in the specification is limited to species anti Her2 scFv domain set forth in SEQ IDNO 9 and anti-mesothelin scFV as set forth in SEQ ID NO: 17 and CD28 transmembrane domain in antigen presenting cells.
Vas-Gath Inc. v. Mahurkar, 19 USPQ2d 111, clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed."
The genus of a polynucleotide encoding any chimeric target factor receptor comprising any cancer antigens-binding domain as set forth in claims and any transmembrane domain in any APC, other than the sequence as set forth in 1 or 9 (anti Her2 scFV) and 17 or 18 (anti-mesothelin scFV) and CD28 transmembrane domain (SEQ ID NO 2 or 10) in dendritic cells, encompassed within the genus have not been disclosed. The specification does not provide a representative number of species of chimeric target factor receptor comprising plurality of cancer antigens-binding domain set forth in claims. The possible structural variations are limitless. The claims lack written description because there is no disclosure of a correlation between function and structure of the different species of beyond those specifically disclosed in the examples in the specification. The specification lacks sufficient variety of species to reflect this variance in the genus showing contemplated biological activity.
In view of the above considerations one of skill in the art would not recognize that applicant was in possession of the necessary common features or attributes possessed by member of the genus of chimeric target factor receptor comprising any cancer antigens -binding domain and any transmembrane domain in any host cell, other than the sequence as set forth in 1 or 9 (anti Her2 scFV) and 17 or 18 (anti-mesothelin scFV) and CD28 transmembrane domain (SEQ ID NO 2 or 10) in antigen presenting cell like dendritic cells. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Response to arguments
Applicants disagree with the rejection arguing a person skilled in the art would readily understand that antibody sequences binding to any desired target factor can be identified by well-known methods, such as screening methods. Applicants argue that, since screening methods using scFvs displayed on phages that were suitable and readily applicable for CAR constructs were already well-established at the time of filing, a person skilled in the art could have appropriately produced the ScFv corresponding to the desired target factor for use in a CAR. To further support the above argument based on ScFv screening, it is noted that claim 8 is being amended to recite that the target factor binding domain comprises "a heavy chain variable region and/or a light chain variable region. Applicants continue to argue that relevant techniques and materials were either well known as common general knowledge or limited at the time of filing, a person skilled in the art could have easily understood and practiced the claimed invention without undue experimentation. Accordingly, Applicant was in possession of the claimed invention across its entire scope as recited in the amended claim. Applicants’ arguments have been fully considered but are not found persuasive.
In response as stated in previous office action, 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.
The claims embrace a genus of antigen presenting cell comprising a polynucleotide encoding any chimeric target factor receptor comprising any target factor-binding domain comprising any heavy-chain variable region and/or any light- chain variable region, wherein the target factor is cancer antigen set forth in claim 1, any transmembrane domain, and any intracellular domain, wherein the TLR intracellular domain is at least one selected from the group consisting of a TLR2 intracellular domain, a TLR3 intracellular domain, and a TLR9 intracellular domain.. Thus, the claims encompass function of receptor is to bind specifically to any of the genus of cancer antigen set forth in claims.
The specification further contemplates a domain containing one or more CDRs of an antibody or T-cell receptor typically has one or more, preferably two, three, four, five or more, more preferably all six of the CDRs of the antibody (e.g., if the CDRs of an antibody are the case, heavy-chain CDR1, heavy-chain CDR2, heavy-chain CDR3, light-chain CDR1, light-chain CDR2, and light-chain CDR3) (see para. 36).
The specification exemplifies a nucleic acid encoding a chimeric target factor receptor construct containing the following disposed in this order from the N-terminus to C-terminus comprises signal peptide of SEQ ID NO: 19 or 20, anti-Her2 scFv domain of SEQ ID NO: 1 or 9, CD29 transmembrane domain of SEQ ID NO:2 or 10 and intracellular domain as set forth in SEQ ID NO: 3, 4, 5, 6 or 7 and further comprising CD40. The specification further teaches a chimeric target factor receptor construct containing a nucleic acid encoding signal sequence of SEQ ID NO: 19, anti-mesothelin scFV as set forth in SEQ ID NO: 17, CD 28 transmembrane domain and TLR1 to TLR9 intracellular domain. Example 2 and 3 teaches dendritic or macrophage cell expressing the chimeric target factor receptor as discussed above. The results indicate that the use of the intracellular domain of TLR for the intracellular domain can increase the expression of MHC class I and MHC class II in response to the target factor. In particular, the degree of activation was found to be high when TLR2, TLR3, or TLR9 was used (Fig. 9).
In response to applicant’s argument that screening methods using scFvs displayed on phages that are suitable and readily applicable for CAR constructs were known to one of skill in art, however, it should be noted that art teaches that the scFv structure affects CAR expression efficiency and stability on T cells and not all scFvs can be expressed as a chimeric antigen receptor (CAR) on T cells (see highlight and page 368) (emphasis added) (Fujiwara et al (BBRC, 2020, 527, 2, 350-357). The teaching of Fujiwara shows that not all target factor binding domain would work due to lack of predictability across claimed genus.
Further, previous office action also established that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of a given antibody. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain the required conformation of the CDRs are required in order to produce a protein having antigen-binding function; and further, that proper association of heavy and light chain variable regions is required in order to form functional binding sites (see Rudikoff et al (Proc Natl Acad Sci USA 1982 Vol 79 page 1979-1983m art of record, Hasegawa (MAbs, 2017 Apr 5;9(5):854-873, Vajdos et al (Journal of Molecular Biology Vol. 320, pp 415-428, 2002 and Wu et al Journal of Molecular Biology Vol. 294, pp 151-162, 1999).
In the instant case, the genus of a polynucleotide encoding any chimeric target factor receptor comprising any cancer antigens-binding domain as set forth in claims and any transmembrane domain in any APC, other than the sequence as set forth in 1 or 9 (anti Her2 scFV) and 17 or 18 (anti-mesothelin scFV) and CD28 transmembrane domain (SEQ ID NO 2 or 10) and intracellular domain of TLR2, TLR3 or TLR9 as set forth in SEQ ID NO 3, 4, 5, 6 or 7 in dendritic cells, encompassed within the genus have not been disclosed. The specification does not provide a representative number of species of APC comprising a nucleic acid encoding CAR comprising plurality of cancer antigens-binding domain set forth in claims. The possible structural variations are limitless. The claims lack written description because there is no disclosure of a correlation between function and structure of the different species of beyond those specifically disclosed in the examples in the specification. The specification lacks sufficient variety of species to reflect this variance in the genus showing contemplated biological activity. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Townsend et al (In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3254) teaches both TLR4 and TLR2 based toll-like receptor signaling domains were evaluated with TLR4 vectors showing higher killing and better efficacy against target cancer (abstract).
Lim et al (PLoS One, 2012, 7(9) , e45185, 1-8, IDS) provide data into the effect of co stimulatory molecules in regulating APC:T cell interactions.
Thomas et al (Mol. Therapy,2023, 1-10)
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANOOP K SINGH/ Primary Examiner, Art Unit 1632
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