DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The present application claims benefit under 35 U.S.C. 119(e) to U.S. Provisional applications 63/297951, filed 1/10/2022; 63/337591, filed 5/2/2022; 63/339960, filed 5/9/2022; 63/342041, filed 5/13/2022; 63/345354, filed 5/24/2022; 63/345369, filed 5/24/2022; 63/345388, filed 5/24/2022; and 63/427128, filed 11/22/2022.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Specifically, no IDS has been filed.
Status of Claims
Claims 1-27 are pending and are being examined on the merits.
Claim Objections
Claims 6, 18 and 25 are objected to because of the following informalities: Claims 6, 18 and 25, line 3, recite “selected from a consisting of”. The claim should say “selected from a group consisting of” as the alternatives that follow the phrase are listed as a grouping. Appropriate correction is required.
Claims 6, 11, 18 and 25 are objected to because of the following informalities: Claims 6, 11, 18 and 25 recite “a single chain antibody variable domain fragment domain”. A single chain antibody variable domain is known as an scFv; it is unnecessary to add “fragment domain” to the description of an scFv, as it is inherently an antibody fragment domain. Appropriate correction is required.
Claims 9, 12, 16 and 23 are objected to because of the following informalities: Claims 9, 12, 16 and 23 recite “a single chain antibody variable domain fragment”. A single chain antibody variable domain is known as an scFv; it is unnecessary to add “fragment” to the description of an scFv, as it is inherently an antibody fragment. Appropriate correction is required.
Claims 6, 11, 18 and 25 are objected to because of the following informalities: Claims 6, 11, 18 and 25 recite “a single chain antibody variable domain fragment domain selected from a consisting of T cell receptor gamma chain binding, T cell receptor delta chain binding”. This phrase is grammatically incoherent. If applicants are intending to claim an scFv which binds a T cell receptor gamma chain, then the use of the verb “binding” should come before the noun. Examiner suggests amending the claim to recite “a single chain antibody variable domain (scFv) which binds a target domain selected from the group consisting of a T cell receptor gamma chain, a T cell receptor delta chain, CD3 delta, CD3 epsilon, CDXAR and JAML”. Appropriate correction is required.
Claim Interpretation
Claims 6, 9, 11, 16, 18, 23 and 25 recite whereby a binding domain is selected from a group consisting of (a) and (b), whereby each of (a) and (b) further recite a “group consisting of.” Claim 9 lists a group consisting of (a), (b) and (c), whereby each of (a), (b) and (c) further recite a “group consisting of.” Each of the claims are being interpreted as requiring a single species of binding domain selected from any of the total species listed in (a), (b) and (c).
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-27 are 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.
Claims 1, 7, 14 and 21 recite a “gamma delta T cell optimized signal peptide”, however does not provide a description of what is required in order for the signal peptide to be “optimized” for a gamma delta T cell. The specifications describe expression codon optimized (ECO) signal peptides, including two unique optimization sequences for the IL2 signal peptide (pg. 4, para. 0049). However, said optimized IL2 signal peptides are not identified or claimed in claim 1; claim 2 limits the signal peptides to mSA, IL2 or hSCF derived peptides, but also does not limit the signal peptide to either of the “optimized” IL2 signal peptides. It is unclear what is required of the gamma delta T cell optimized signal peptide of claim 1. What are the structural or functional requirements for the signal peptide to be considered optimized? If a signal protein enhances expression of a protein by 1% in a gamma/delta T cell, is that sufficient to meet the limitation of an “optimized” signal peptide; or does any signal peptide that functionally promotes expression of a secretable protein in a gamma/delta cell qualify as a gamma/delta T cell optimized signal peptide? Is there a particular shared structural feature of an optimized signal peptide that imparts optimized function in a gamma/delta T cell versus alternative species of T cells? It is unclear what structural/functional limitations are required to meet the claim limitation of an “optimized” signal peptide. As the metes and bounds of the claims are unclear, claims 1, 7, 14 and 21 are rendered indefinite. Claims 2, 8 15 and 22 depend from claims 1, 7, 14 and 21, respectively; and each limits the signal peptide to one of mSA, IL2 and hSCF. However, claims 2, 8, 15 and 22 do not provide a specific structure or definition of what constitutes an “optimized” signal peptide. Therefore claims 2, 8, 15 and 22 do not rectify the indefiniteness of claim 1, and claims 2, 8, 15 and 22 are also rejected. Similarly, claims 3-6, 9-13, 16-20 and 23-27 depend from rejected claims 1, 7, 14 and 21, yet fail to rectify the issue of indefiniteness, thus claims 3-6, 9-13, 16-20 and 23-27 are also rejected.
Claims 6, 11, 18-20 and 25 are 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.
Claims 6, 11, 18 and 25 recite wherein the gamma delta T cell binding domain is selected from (a) a scFv selected from the group consisting of “T cell receptor gamma chain binding, T cell receptor delta chain binding, CD3delta, CD3 epsilon, CDXAR and JAML”. The phrase “T cell receptor gamma chain binding” is interpreted to be a scFv that binds a TCR gamma chain. However, it is unclear if CD3delta, CD3 epsilon, CDXAR and JAML refer to the use of any one of these species in the invention, or if the claim is referencing an scFv which binds to, for example, CD3 epsilon. The species of the grouping that proceed CD3 epsilon recite “binding”, such that it is referencing a scFv that binds to the recited domain, but no use of binding, or binder, or anti-CD3ε, makes it unclear if the species of the claim is CD3 epsilon, or antibodies directed against CD3 epsilon (i.e. an anti-CD3ε scFv). In grouping (b), all the species listed are scFvs or ligands. Thus, it is unclear if CD3 epsilon refers to the use of CD3 epsilon in the invention or an anti-CD3ε binding domain for use in the invention. As the metes and bounds of the claims are unclear, claims 6, 11, 18 and 25 are rendered indefinite. Claims 19-20 depend from rejected claim 18 but fail to rectify the issue of indefiniteness, therefore claims 19-20 are also rejected.
Claim 7-13 are 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 7 recites “an engineered gamma delta T cell capable of secreting at least one therapeutic protein that has been expression cassette optimized,”. It is unclear what “expression cassette optimized” is referring to. First, is the expression cassette optimizing the therapeutic protein or the engineered gamma delta T cell? Second, does the expression cassette also comprise an optimization? Third, what structural or functional differences are required to meet the limitation of an “optimized” expression cassette, or an “optimized” gamma delta T cell or an “optimized” therapeutic protein? It is unclear what structural/functional limitations are required to meet the claim limitation of “expression cassette optimized”. As the metes and bounds of the claim are unclear, claim 7 is rendered indefinite. Claims 8-13 depend from claim 7 but fail to rectify the issue of indefiniteness, therefore claims 8-13 are also rejected.
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 1-6, 14-18 and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Alvarez Vallina et al., (WO 2021/165248; published 8/26/2021) and Attallah et al. (Protein Expression and Purification, 2017 (132)).
WO ‘248 teaches a secretable bispecific antibody comprising an anti-CD19 scFv and an anti-CD3 scFv, and engineered T cells secreting the bispecific antibody (abstract). WO ‘248 teaches that the tandem scFvs are also known as bispecific T cell engagers (BiTE), and consist of two scFvs connected by a flexible linker on a single polypeptidic chain (pg. 1, lines 22-24). WO ‘248 teaches that the secretable BiTE comprises the anti-CD19 A3B1 scFv and the anti-CD3 OKT3 scFv, and wherein the OKT3 anti-CD3 scFv binds the CD3ε subunit (pg. 6, lines 24-25 and 28-29). WO ‘248 teaches that suitable linkers for linking the two scFvs include (G4S)n (pg. 8, lines 14-16). WO ‘248 teaches the construct also comprises a signal peptide, which may be a human kappa light chain signal peptide or an IL-2 signal peptide (pg. 8, lines 5-11). Thus, WO ‘248 teaches a bispecific construct comprising from N-terminus to C-terminus, a signal peptide which is cleaved off prior to secretion (IL-2 peptide), a tumor cell-binding protein domain (anti-CD19 scFv), a linker (G4S), and a T cell binding domain (anti-CD3 scFv).
Regarding the “gamma delta T cell optimized” signal peptide, the instant specifications describe “exemplary” signal peptides of the invention include IL-2 signal peptides (which are not specifically defined), and modified serum albumin (mSA) peptides of instant SEQ ID NO: 3 (specifications, pg. 21, para. 0147). In the event that the IL-2 signal peptide of WO ‘248 does not qualify as a gamma delta T cell optimized signal peptide, reference is made to Attallah et al., (Protein Expression and Purification).
Attallah et al. teaches a highly efficient modified human serum albumin signal peptide to secrete proteins in cells derived from different mammalian species (title). Attallah teaches the mSA peptide has the amino acid sequence MKWVTFISLLFLFSSSSRA (pg. 28, Table 1), which is 100% identical in amino acid sequence to the mSA peptide of instant SEQ ID NO: 3. Attallah teaches the expression of a scFv-Fc fusion protein in multiple cell lines, wherein alternative signal peptides were used for comparison, including a human kappa chain peptide and the mSA peptide (abstract). Attallah teaches the mSA signal peptide was successful in directing the secretion of the active proteins in different types of mammalian cells (abstract), including being 6-7 times more effective than the human kappa chain signal peptides (pg. 30, Fig. 2B).
It would have been obvious to one of skill in the art to modify the secretable anti-CD19/anti-CD3 bispecific construct, comprising a kappa light chain signal peptide, of WO ‘248 to instead comprise the mSA signal peptide of Attallah et al. One would have been motivated to do so given that the mSA signal peptide of Attallah increased secretion pathway expression of the protein by 6-7 fold over a kappa light chain signal peptide, as taught by Attallah et al. There would have been a reasonable expectation for success given that the mSA signal peptide and the kappa light chain signal peptide are substitutable alternatives for the same use as taught by Attallah et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 1-6, the combination protein of WO ‘248 and Attallah, comprising a mSA signal peptide, an anti-CD19 scFv, a G4S linker, and an anti-CD3 scFv, makes obvious the protein of instant claims 1-6.
Regarding claims 14-18, the combination protein of WO ‘248 and Attallah is described above. WO ‘248 also teaches a method of preparation of T cells secreting the bispecific construct, including the use of lentiviral vectors encoding the construct of the invention (pg. 11, lines 15-33). As the vector encodes all the elements of the bispecific construct, whereby the construct is secreted by T cells, the combination of WO ‘248 and Attallah make obvious instant claims 14-18.
Regarding claims 21-25, WO ‘248 teaches that methods of introducing exogenous polynucleotides into a host cell include nucleoside-modified mRNA and RNA transfection, as well as using RNA vectors (pg. 9, lines 8-15). WO ‘248 highlights that methods of transducing T cells by RNA electroporation, whereby the T cells secrete an anti-CD3/anti-CD19 BiTE are known in the art (pg. 2, lines 5-10). Thus, WO ‘248 teaches recombinant synthetic mRNA encoding the secretable bispecific construct, and the combination of WO ‘248 and Attallah make obvious instant claims 21-25.
Claims 7-12, 19-20 and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Alvarez Vallina et al., (WO 2021/165248; published 8/26/2021) and Attallah et al. (Protein Expression and Purification, 2017 (132)) as applied to claims 1-6, 14-18 and 21-25 above, and further in view of Bedoya et al., (US 2017/0137783; published 5/18/2017).
The secretable bispecific protein of the combination of WO ‘248 and Attallah et al., comprising an mSA signal peptide, an anti-CD19 scFv, a G4S linker, and an anti-CD3 scFv is described above. Further described are vectors and synthetic mRNAs encoding the protein. However, neither WO ‘248 nor Attallah describe the selected promoter region of the expression cassette encoding the construct, nor the inclusion of an shRNA domain targeting an HLA molecule, specifically the beta-2-microglobulin (i.e., B2M) or CIITA. Nonetheless, selection of a preferred promoter and/or inclusion of an anti-HLA component shRNA domain are common practice in the art of vector construction regarding T cell genetic engineering, and do not represent a patentable point of novelty over routine optimization. See Bedoya et al. below.
Bedoya et al. teaches methods of making immune effector cells that can be engineered to express a chimeric antigen receptor (CAR) and methods of treatment using the same (abstract). Bedoya teaches the exemplary effector cells of the invention include T cells and gamma/delta T cells (pg. 2, para. 0013). Bedoya teaches nucleic acids encoding the CAR, which are DNA vectors or RNA vectors, including lentivirus vectors (pg. 2, para. 0020); and also includes (in vitro transcription) IVT RNA, which encompasses synthetic mRNA (pg. 3, para. 0031). Bedoya teaches an example of a promoter that is capable of expressing the CAR encoding nucleic acid molecule in a mammalian T cell is the Ef1α promoter (pg. 71, para. 0581), among other alternative promoters (paras. 0582-0583). Bedoya teaches the vector may also include a signal sequence to facilitate secretion (pg. 72, para. 0586). Bedoya also teaches that the T cell can be engineered such that it does not express a functional HLA on its surface, whereby downregulation of HLA may be accomplished by reducing or eliminating expression of beta-2-microglobulin (B2M; pg. 35, para. 0383); and that shRNA may be used to knock out or knock down the subunit (pg. 35, para. 0384). Bedoya teaches that methods of shRNA-mediated HLA knock out, and expression systems for shRNAs, are known in the art (pg. 35, paras. 0387-0388); and that applying such methods are a means of making the T cells allogenic (pg. 35, para. 0371; pg. 23, para. 0272).
It would have been obvious to one of skill in the art to modify the vector and expression cassette encoding the secretable bispecific construct of WO ‘248 and Attallah to encode an Ef1α promoter and/or to encode an shRNA targeting B2M. One would have been motivated to do so in the process of routine optimization based on the desired features of the engineered protein expressed in a gamma/delta T cell; including increased expression of the protein and/or knock out of an HLA in order to make the engineered T cells which express the protein allogeneic for a patient population, as taught by Bedoya et al. There would have been a reasonable expectation for success given that use of these elements are common practice in the art of genetically engineering T cells to express a recombinant protein. Thus, the invention as a whole was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 19-20 and 26-27; the combination of WO ‘248, Attallah and Bedoya make obvious using a Ef1α promoter and/or incorporating a domain encoding an shRNA targeting B2M for knock out in gamma/delta T cells. Said modifications may be made in the design of the suitable vector encoding the construct, or in a synthetic mRNA molecule. Thus, WO ‘248, Attallah and Bedoya make obvious claims 19-20 and 26-27.
Regarding claims 7-12, the combination protein of WO ‘248 and Attallah is described above. However, neither WO ‘248 nor Attallah disclose wherein the construct is expressed in a gamma/delta T cell. The CAR construct of Bedoya is also described above. Bedoya teaches the CAR construct may be bispecific (pg. 41, para. 0443). Specifically Bedoya teaches “in an embodiment a bispecific antibody molecule comprises a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a first epitope and a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a second epitope,” (pg. 41, para. 0444). Thus, Bedoya contemplates a bispecific scFv construct. Bedoya teaches the nucleic acid encoding the construct comprises a leader (signal) peptide (pg. 53, para. 0521), which may facilitate secretion (pg. 72, para. 0586), and comprises G4S linkers (pg. 54, para. 0537). Bedoya teaches the CARs are expressed in T cells, and that exemplary T cells include gamma/delta T cells (pg. 2, para. 0013).
It would have been obvious to one of skill in the art to express the secretable BiTE construct of WO ‘248 and Attallah in gamma/delta T cells. One would have been motivated to do so given that gamma/delta T cells provide an exemplary T cell type for expression of recombinant therapeutic proteins, as taught by Bedoya et al. There would have been a reasonable expectation for success given that Bedoya teaches the expression of a bispecific CAR construct in gamma/delta T cells, and that the bispecific CAR construct of Bedoya comprises a smaller dual scFv BiTE construct as its antigen binding domain, whereby the format of a dual scFv antigen binding domain is the same as the bispecific scFv construct of WO ‘248 and Attallah. Thus, it is obvious that the skilled artisan could engineer a gamma/delta T cell to express a BiTE-type construct following the same guidance for expressing a bi-specific CAR construct in the same cells.
Regarding claims 7-12, the engineered gamma/delta T cells of WO ‘248, Attallah and Bedoya, comprising the bispecific construct of WO ‘248 and Attallah, wherein the construct comprises an mSA signal peptide, an anti-CD19 scFv, a G4S linker, and an anti-CD3 scFv makes obvious the engineered gamma/delta T cells of claims 7-10 and 12. Further, as the anti-CD3 scFv is derived from OKT3, it binds to CD3ε, and thus makes obvious instant claim 11.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Alvarez Vallina et al., (WO 2021/165248; published 8/26/2021) over Attallah et al. (Protein Expression and Purification, 2017 (132)) and Bedoya et al., (US 2017/0137783; published 5/18/2017) as applied to claims 1-12 and 14-27 above, and further in view of Madec et al., (US 2011/0262423; published 10/27/2011).
The reasons why claims 1-12 and 14-27 are rejected over WO ‘248, Attallah and Bedoya are described above. Specifically, the combination of WO ‘248, Attallah and Bedoya make obvious a secretable bispecific protein (e.g. BiTE) comprising an mSA signal peptide, an anti-CD19 scFv, a G4S linker, and an anti-CD3 scFv, and wherein the secretable bispecific protein is expressed in a gamma/delta T cell. However, the combination of WO ‘248, Attallah and Bedoya do not teach whereby the tumor cell binding domain of the bispecific protein is, for example, a somatostatin ligand instead of an anti-tumor antigen scFv.
Madec et al. teaches polypeptides encoding a fusion protein, wherein the fusion protein comprises (i) a bioactive, non-cytotoxic protease, (ii) a targeting moiety and (iii) a translocation domain, for use as a cancer therapeutic (pg. 1, paras. 0011-0014; pg. 8, para. 0096). Regarding the targeting moiety, Madec teaches this component binds the polypeptide of the invention to a cancer cell by targeting a binding site on the cancer cell, thereby providing selectivity of the polypeptide to this species of target cell over other cells (pg. 3, paras. 0031-0032). Madec teaches the targeting moiety may be an antibody, including antibody fragments such as scFv; or alternatively, they may be binding scaffolds which bind to receptors on a cancer cell (pg. 3, para. 0032). Madec teaches the targeting moiety may bind a receptor on a cancer cell, such as a somatostatin (SST) receptor (pg. 3, paras. 0033-0034). Madec teaches the targeting moiety that binds to a SST receptor includes SST peptides and cortistatin peptides, as well as SST-14 and SST-28 peptides (pg. 4, para. 0038). Madec teaches the SST-28 peptide comprises the amino acid sequence of SANSNPAMAPRERKAGCKNFFWKTFTSC (pg. 14, para. 0178), which comprises 28 amino acids of the full length somatostatin (SST) ligand (pg. 14, para. 0174). The amino acid sequence of the SST-28 peptide of Madec is 100% identical to the SST-28 ligand of instant SEQ ID NO: 73 (specs., pg. 71, para. 0503). Madec embodies the SST-28 ligand peptide in a fusion protein, for example see pgs. 39-40, examples 16-17. Thus, Madec teaches fusion proteins comprising a targeting moiety, and that the targeting moiety may be either a antibody scFv antigen binding domain that targets a tumor antigen or a SST-28 peptide ligand that targets a SST receptor expressed on a tumor cell.
It would have been obvious to one of skill in the art to substitute the CD19 tumor cell-binding domain of the secretable CD19/CD3 BiTE protein, expressed in gamma/delta T cells, of WO ‘248, Attallah and Bedoya with a SST-28 peptide targeting SST receptors on tumor cells. One would have been motivated to do so for the purpose of targeting the therapeutic protein selectively to tumor cells, as taught by Madec et al. There would have been a reasonable expectation for success given that tumor cell targeting moieties may be alternatively selected from either an anti-tumor antigen antibody scFv domain or a SST receptor ligand fragment domain such as SST-28, as taught by Madec et al.; and that such SST-28 fragments were successfully engineered into fusion proteins as demonstrated by Madec et al. Thus, the invention as a whole was prima facie obvious to one of skill in the art.
Section 2143 of the MPEP provides rationales supporting a conclusion of obviousness including 2143(I)(A)- combining prior art elements according to known methods to yield predictable results, and (B)- simple substitution of one known element for another to obtain predictable results. In this case, bispecific T cell engagers (BiTEs), and other bispecific constructs, are known in the art to comprise a tumor targeting domain directed against a tumor associated antigen for the purpose of directing the bispecific protein to the tumor cells. As various tumor associated antigens are known in the art, so too are there numerous anti-TAA binding constructs, including antibodies, antibody scFvs and ligands that bind receptors expressed on tumor cells. In constructing a fusion protein comprising an anti-tumor binding domain, Madec teaches the binding domain may be either an antibody scFv directed against a tumor, or a ligand, or ligand fragment, directed against a somatostatin receptor. Thus, Madec teaches that the tumor targeting domains are equivalents in the art for the purpose of targeting a protein construct to a tumor, and are substitutable across various embodiments for the same purpose. As the combination of WO ‘248, Attallah and Bedoya make obvious a secretable bispecific protein (e.g. BiTE) comprising an mSA signal peptide, an anti-CD19 scFv, a G4S linker, and an anti-CD3 scFv, and wherein the secretable bispecific protein is expressed in a gamma/delta T cell; Madec makes obvious substituting a SST-28 ligand fragment domain in place of the anti-CD19 scFv domain of the protein. Thus, the combination of WO ‘248, Attallah, Bedoya and Madec make obvious instant claim 13.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Fisher et al., (WO 2021/148788; published 7/29/2021). Fisher et al. teaches “armored” gamma/delta T cells which express a secretable antigen binding protein. The antigen binding protein of Fisher has a scFv-Fc format, whereby the scFv domain targets a tumor antigen, and the Fc domain induces antibody-dependent cellular cytotoxicity via recruitment of transduced and non-transduced effector cells. Thus, the difference is that the binding protein of the instant invention is effectively a BiTE, wherein scFv-1 binds a tumor antigen and scFv-2 binds a T cell receptor, whereas the binding protein of Fisher comprises an scFv which binds a tumor antigen and an Fc which binds an effector cell.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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/JAMES RYLAND MELCHIOR/ Examiner, Art Unit 1644
/DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644