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 .
This application has been transferred to primary examiner Quang Nguyen, Ph.D. in AU 1631.
Applicant’s amendment filed on 08/27/2025 has been entered.
Claims 1-2, 17-23, 25-26, 28, 31-36, 40-41, 43, 52, 62-63, 66, 69, 73, 81-83 are pending in the present application.
Applicant’s election without traverse of Group II, drawn to a recombinant nucleic acid comprising a nucleotide sequence that encodes the chimeric polypeptide of claim 1, compositions related the same recombinant nucleic acid and methods related to the same recombinant nucleic acid, in the reply filed on 08/27/2025 is acknowledged.
Accordingly, claims 1, 17-23, 25-26, 28, 31-36 and 40-41 were withdrawn from further consideration because they are directed to a non-elected invention (a chimeric polypeptide of the present application).
Therefore, claims 43, 52, 62-63, 66, 69, 73 and 81-83 are examined on the merits herein.
Claim Objections
Claim 43 is objected to because it is dependent on the non-elected claim 1. Additionally, claim 43 is also objected to because the phrase “comprising a sequence having at least 90% identity to SEQ ID NO: 56” in claim 1 is recited twice.
Claims 52 is objected to because it contains the embodiment (a) of a non-elected invention.
Similarly, claims 66, 69, 73, 81-83 are objected to because they contain embodiments of a non-elected invention drawn to a chimeric polypeptide.
Claim Rejections - 35 USC § 112 (Lack of Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 43, 52, 62-63, 66, 69, 73 and 81-83 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 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc). Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), 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.” Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1117. The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed. ”Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1116.
The instant claims encompass a recombinant nucleic acid comprising a nucleotide sequence that encodes a chimeric polypeptide comprising from N-terminus to C-terminus: a) an extracellular ligand-binding domain having a binding affinity for any selected ligand of any type (e.g., a ligand is a protein, a carbohydrate, a lipid, a lipoprotein, a glycolipid, or a lipopolysaccharide; see paragraph [0069]); b) a linking polypeptide comprising a Notch juxtamembrane domain (JMD) having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the sequence set forth in SEQ ID NO: 12, 13, 14, 16, or 17, wherein a LIN-12-Notch repeat (LNR) and/or a heterodimerization domain (HD) of a Notch receptor has been deleted; c) a transmembrane domain having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the transmembrane domain of a Type I transmembrane receptor and comprising one or more ligand-inducible proteolytic cleavage sites; and d) an intracellular domain comprising a zinc finger-containing transcriptional effector (ZTE) comprising a sequence having at least 90% identity to SEQ ID NO: 56 (399 amino acids), wherein binding of the selected ligand to the extracellular domain binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain; a recombinant cell comprising the same recombinant nucleic acid; a cell culture comprising the same recombinant cell; a kit or a pharmaceutical composition comprising the same recombinant nucleic acid and/or the same recombinant cell; a method for making an engineered cell using the same recombinant nucleic acid; and a method for modulating an activity of a target cell in an individual or a method for the treatment of any health condition in an individual using an effective number of the same recombinant cells.
Apart from disclosing the design and construction of a family of chimeric Notch receptors with zinc finger-containing transcriptional effector in Tables 1-2, including chimeric Notch receptors comprise the following elements from the N-terminus to C-terminus: an antiCD19 scFv as an extracellular domain (ECD), the truncated Notch juxtamembrane domain (N-JMD) of SEQ ID NO: 11, the Notch 1 transmembrane domain (TMD) of SEQ ID NO: 31, the stop-transfer-sequence (STS) of SEQ ID NO: 39 or 40, and the intracellular domain containing a zinc-finger transcriptional effector (ZTE) with SEQ ID NO: 56, wherein the chimeric ZTE-containing Notch receptors are expressed and demonstrated to be functional in reporter+ Jurkat cells comprising an 8xZF3 response element with a synthetic sbyTATA promoter operably linked to mCitrine reporter gene upon activation by CD19 ligand binding (see at least Examples 1, 7; and Figs. 1-2); the instant specification failed to describe sufficiently other encoded chimeric ZTE-containing Notch receptors comprising an extracellular ligand-binding domain having a binding affinity for selected ligands other than a CD19 protein, let alone for other proteins and/or non-protein ligands (e.g., a carbohydrate, a lipid, a lipoprotein, a glycolipid, or a lipopolysaccharide) and/or other transmembrane domains having at least about 80% sequence identity to any transmembrane domain of a Type I transmembrane receptor and comprising one or more any other ligand-inducible proteolytic cleavages, wherein binding of the selected ligand to the extracellular binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain as encompassed broadly by the instant claims. The instant specification merely stated generically “Non-limiting examples of suitable ligand types include cell surface receptors, adhesion proteins, carbohydrates, lipids, glycolipids, lipoproteins, and lipopolysaccharides that are surface-bound integrins, mucins, and lectins. In some embodiments, the ligand is a protein. In some embodiments, the ligand is a carbohydrate” (paragraph [0069]); and “In some embodiments, the TMD includes an amino acid sequence exhibiting at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity to one or more of SEQ ID NOS: 29-38” (paragraph [0100]). For example, what essential or critical elements do other extracellular ligand-binding domains having a binding affinity for a select ligand that is a lipid, a carbohydrate, a lipoprotein, or a lipopolysaccharide possess such that in the format of an encoded chimeric ZTE-containing Notch receptor of the present application the binding of the selected ligand to the extracellular binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain? Similarly, apart from the disclosed TMDs of SEQ ID NOS: 29-38 which specific modifications (e.g., substitution(s), insertion(s), deletion(s), or a combination thereof) in any one of these SEQ ID NOs that are amenable for modifications as long as the modified TMDs having at least about 80% to the transmembrane domain of a Type I transmembrane receptor and comprising one or more ligand-inducible proteolytic cleavage site, and that the modified TMDs still retain the ability for cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain upon binding of a selected ligand to the extracellular binding domain? Hudecek et al (Cancer Immunol. Res. 3:125-135, 2014) analyzed the influence of length and composition of IgG-derived extracellular spacer domains on the function of chimeric antigen receptors (CARs), and they demonstrated that CD19-CARS with a long spacer from IgG4 hinge-CH2-CH3 are functional in vitro but lack antitumor in vivo due to the interaction between the Fc domain within the spacer and the Fc receptor-bearing myeloid cells, leading to activation-induced T-cell death. However, in vivo persistence and antitumor effects of CAR-T cells with a long spacer can be restored by modifying distinct regions in the CH2 domain that are essential for Fc receptor binding, and modifications that abrogate binding to Fc receptors are crucial for CARs in which long spacer is obligatory for tumor recognition such as a ROR1-specific CAR (see at least abstract). Hudecek et al also stated “A study of a CD22-specific CAR suggested that the distance of the target epitope from the cell membrane is an important parameter (36), and tumor recognition by 5T4- and NCAM-specific CARs that recognize membrane-proximal epitopes was improved with a long spacer (15). In the case of CD19-CARs, our data demonstrate that target recognition in vitro will accommodate a wide range of spacer lengths from 12 to 229 aa. This may reflect the structure and/or location of the CD19 epitope recognized by the FMC63 mAb or the high density of the CD19 molecule on tumor cells [37]. Even though CD19+ tumor cells are recognized in vitro, we observed more efficient cytokine production and proliferation of CAR-T cells that contain a short 12-aa spacer compared with those with intermediate (119 aa) or long (229 aa) spacers. We previously demonstrated a similar hierarchy of tumor recognition for ROR1-CARs derived from the 2A1 and R12 scFvs that recognize an epitope in the Ig/Frizzled domain of ROR1 and function optimally with a short extracellular spacer (20). However, the R11 ROR1-CAR that is specific for an epitope in the putatively more membrane-proximal Kringle domain of ROR1 requires a long spacer for recognition of ROR1+ tumor cells. Thus, spacer length can affect tumor recognition depending on the molecule and epitope being targeted” (last sentence of first paragraph on left column at page 131). Thus, the teachings of Hudecek et al highlight at least the unpredictability in the design and construct of a chimeric antigen receptor (CAR), and given that each new scFv and target molecule defines a unique distance from a tumor cell plasma membrane, the adjustment of CAR spacers are unique to each construct and derived via empirical testing of spacer length variants.
Since the prior art before the effective filing date of the present application (09/24/2019) failed to provide sufficient guidance and/or written description for the above issues as evidenced at least by the teachings of Morsut et al (Cell 164:780-791, 2016), Roybal et al (Cell 167:419-432, 2016) and Lim et al (US 2019/0202918; IDS); it is incumbent upon the instant specification to do so. Furthermore, the instant specification also fails to provide and describe at least a representative number of species for a broad genus of a recombinant nucleic acid comprising a nucleotide sequence that encodes a chimeric polypeptide having the recited elements a)-d), wherein binding of a selected ligand to the extracellular binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain, compositions comprising the same recombinant nucleic acid, methods of making and using the same compositions as claimed broadly. The claimed invention as a whole is not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which are not conventional in the art as of Applicants’ filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641, 1646 (1998). The skilled artisan cannot envision at least a representative number of species for a broad genus of a recombinant nucleic acid comprising a nucleotide sequence that encodes a chimeric polypeptide having the recited elements a)-d), wherein binding of a selected ligand to the extracellular binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain, compositions comprising the same recombinant nucleic acid, methods of making and using the same compositions as claimed broadly; and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 112 (Enablement)
Claims 43, 52, 62-63, 66, 69, 73 and 81-83 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention.
The factors to be considered in the determination of an enabling disclosure have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art and the breadth of the claims. Ex parte Forman, (230 USPQ 546 (Bd Pat. Appl & Unt, 1986); In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988)).
When read in light of the specification, the sole purpose for a recombinant nucleic acid comprising a nucleotide sequence that encodes the chimeric polypeptide of the present application, which is a chimeric Notch receptor containing a synthetic zinc finger transcriptional effector (synZTE) molecule, engineered to modulate gene expression and cellular activities in a ligand-dependent manner, wherein the synZTE is designed to bind orthogonal DNA target sequences, and has little or no binding activity to existing DNA sequences in organisms; and further requires a response element that includes: (a) a ZFA target sequence, (b) an engineered response promoter operably linked to the ZF target sequence, and (c) a polynucleotide of interest (see at least Abstract; particularly paragraphs [0008],[0066] and [0144]-[0145]; and Fig. 2). Reproduced Fig. 2 summarizes the functionality of an encoded chimeric Notch receptor containing a synthetic zinc finger transcriptional effector (synZTE) molecule.
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The instant specification stated specifically “The targetable DNA sequences are operably linked to the promoters such that the occupancy of synTFs on the targetable DNA sequences regulates the activity of the promoter in gene expression. The combination of synTFs and a targetable DNA sequence-promoter forms a unique expression system that is artificial, scalable, and regulatable, for the expression of desired genes placed within the expression system, with no or minimal effects on the expression of endogenous genes, meaning no or minimal off-site gene regulation of endogenous genes” (paragraph [0145]). The instant claims are not enabled for the reasons discussed below.
1. The breadth of the claims
Claims 43, 52, 62, 66 and 82-83 encompass a recombinant nucleic acid comprising a nucleotide sequence that encodes a chimeric polypeptide comprising from N-terminus to C-terminus: a) an extracellular ligand-binding domain having a binding affinity for any selected ligand of any type (e.g., a ligand is a protein, a carbohydrate, a lipid, a lipoprotein, a glycolipid, or a lipopolysaccharide; see paragraph [0069]); b) a linking polypeptide comprising a Notch juxtamembrane domain (JMD) having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the sequence set forth in SEQ ID NO: 12, 13, 14, 16, or 17, wherein a LIN-12-Notch repeat (LNR) and/or a heterodimerization domain (HD) of a Notch receptor has been deleted; c) a transmembrane domain having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the transmembrane domain of a Type I transmembrane receptor and comprising one or more ligand-inducible proteolytic cleavage sites; and d) an intracellular domain comprising a zinc finger-containing transcriptional effector (ZTE) comprising a sequence having at least 90% identity to SEQ ID NO: 56 (399 amino acids), wherein binding of the selected ligand to the extracellular domain binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain; a recombinant cell comprising the same recombinant nucleic acid; a cell culture comprising the same recombinant cell; a kit or a pharmaceutical composition comprising the same recombinant nucleic acid and/or the same recombinant cell. Claim 63 encompasses a method for making an engineered cell comprising transducing a cell capable of protein expression with the same recombinant nucleic acid. Claim 73 encompasses a method for modulating (e.g., increasing or decreasing) an activity of a cell (in vitro or in vivo) comprising contacting the recombinant cell with the selected ligand, wherein binding of the selected ligand to the extracellular ligand-binding domain results in cleavage of a ligand-inducible proteolytic cleavage site and release of the intracellular domain, wherein the release of the intracellular domain results in modulation of an activity of the recombinant cell.
Claim 69 encompasses a method for modulating (e.g., increasing or decreasing) an activity of a target cell in an individual comprising administering to the individual an effective number of recombinant cells of any cell type derived from any source (e.g., a prokaryote cel, an animal cell, or a plant cell) as long as the recombinant cells comprise the same recombinant nucleic acid. Claim 81 encompasses a method for the treatment of any health condition in an individual in need thereof using an effective number of recombinant cells of any cell type derived from any source (e.g., a prokaryote cel, an animal cell, or a plant cell) as long as the recombinant cells comprise the same recombinant nucleic acid, wherein the recombinant cells treat the health condition in the individual.
2. The state and the unpredictability of the prior art
Before the effective filing date of the present application (09/24/2019), virtually nothing was known about a recombinant nucleic acid comprising a nucleotide sequence that encodes the chimeric polypeptide having the elements a)-d) as recited in claim 1, particularly one with an intracellular domain comprising a zinc finger-containing transcription effector (ZTE) comprising a sequence having at least 90% identity to SEQ ID NO:56, as evidenced at least by the teachings of Morsut et al (Cell 164:780-791, 2016), Roybal et al (Cell 167:419-432, 2016) and Lim et al (US 2019/0202918; IDS). Moreover, Hudecek et al (Cancer Immunol. Res. 3:125-135, 2014) already highlighted at least the unpredictability in the design and construct of a chimeric antigen receptor (CAR), and given that each new scFv and target molecule defines a unique distance from a tumor cell plasma membrane, the adjustment of CAR spacers is unique to each construct and derived via empirical testing of spacer length variants. Please also note that the physiological art is recognized as unpredictable (MPEP 2164.03).
3. The amount of direction or guidance provided
Apart from disclosing the design and construction of a family of chimeric Notch receptors with zinc finger-containing transcriptional effector in Tables 1-2, including chimeric Notch receptors comprise the following elements from the N-terminus to C-terminus: an antiCD19 scFv as an extracellular domain (ECD), the truncated Notch juxtamembrane domain (N-JMD) of SEQ ID NO: 11, the Notch 1 transmembrane domain (TMD) of SEQ ID NO: 31, the stop-transfer-sequence (STS) of SEQ ID NO: 39 or 40, and the intracellular domain containing a zinc-finger transcriptional effector (ZTE) with SEQ ID NO: 56, wherein the chimeric ZTE-containing Notch receptors are expressed and demonstrated to be functional in reporter+ Jurkat cells comprising an 8xZF3 response element with a synthetic sbyTATA promoter operably linked to mCitrine reporter gene upon activation by CD19 ligand binding (see at least Examples 1, 7; and Figs. 1-2); the instant specification failed to provide sufficient guidance for an ordinary skilled artisan on how to make and use the recombinant nucleic acid, the recombinant cell, a kit and/or a pharmaceutical composition comprising simply a nucleotide sequence encoding a chimeric Notch receptor containing a synthetic zinc finger transcriptional effector (synZTE) molecule as claimed, particularly without a response element comprising: (a) a ZFA target sequence, (b) an engineered response promoter operably linked to the ZF target sequence, and (c) a polynucleotide of interest. For example, without the presence of such a response element the claimed compositions comprising the recombinant nucleic acid would not result or elicit any useful response, let alone a response that yield any desired therapeutic effect for treating any health condition in an individual in need thereof. Particularly, the encoded chimeric Notch receptor containing a synthetic zinc finger transcriptional effector (synZTE) molecule is engineered to modulate gene expression and cellular activities in a ligand-dependent manner, wherein the synZTE is designed to bind orthogonal DNA target sequences, and has little or no binding activity to existing DNA sequences in organisms. Moreover, with respect to the encoded chimeric ZTE-containing Notch receptor with the intracellular domain of SEQ ID NO: 56 that is a zinc finger transcriptional activator (Example 1 and Figs. 1-2), the instant specification also fails to provide sufficient guidance for a skill in the art how to modulate (increase or decrease), particularly decreasing or suppressing any activity of a target cell in an individual (in vivo) and/or in vitro, even in the presence of a response element comprising: (a) a ZFA target sequence, (b) an engineered response promoter operably linked to the ZF target sequence, and (c) a polynucleotide of interest; let alone without such response element as encompassed broadly by claims 69 and 71. Furthermore, the instant specification also fails to provide sufficient guidance for a skill in the art on how to administering an effective number of recombinant cells derived from any source (e.g., prokaryotic cells, plant cells, and/or xenogeneic animal cells) into an individual (e.g., a human), including an individual in need of treatment of any health disease, particularly on how to overcome the vigorous adverse xenogeneic immune rejection, such that the transplanted recombinant cells comprising the recombinant nucleic acid along with its appropriate response element survive for a sufficient period of time to yield any desired therapeutic effect or result, let alone in the absence of any response element as encompassed broadly by claims 69 and 81.
With respect to the breadth of the recombinant nucleic acid comprising a nucleotide sequence that encodes the claimed chimeric polypeptide of the present application, the instant specification fails to provide sufficient guidance for a skill in the art on how to make and use other encoded chimeric ZTE-containing Notch receptors comprising an extracellular ligand-binding domain having a binding affinity for selected ligands other than a CD19 protein, let alone for other proteins and/or non-protein ligands (e.g., a carbohydrate, a lipid, a lipoprotein, a glycolipid, or a lipopolysaccharide) and/or other transmembrane domains having at least about 80% sequence identity to any transmembrane domain of a Type I transmembrane receptor and comprising one or more any other ligand-inducible proteolytic cleavages, wherein binding of the selected ligand to the extracellular binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain as encompassed broadly by the instant claims. The instant specification merely stated generically “Non-limiting examples of suitable ligand types include cell surface receptors, adhesion proteins, carbohydrates, lipids, glycolipids, lipoproteins, and lipopolysaccharides that are surface-bound integrins, mucins, and lectins. In some embodiments, the ligand is a protein. In some embodiments, the ligand is a carbohydrate” (paragraph [0069]); and “In some embodiments, the TMD includes an amino acid sequence exhibiting at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity to one or more of SEQ ID NOS: 29-38” (paragraph [0100]). For example, what essential or critical elements do other extracellular ligand-binding domains having a binding affinity for a select ligand that is a lipid, a carbohydrate, a lipoprotein, or a lipopolysaccharide possess such that in the format of an encoded chimeric ZTE-containing Notch receptor of the present application the binding of the selected ligand to the extracellular binding domain induces cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain? Similarly, apart from the disclosed TMDs of SEQ ID NOS: 29-38 which specific modifications (e.g., substitution(s), insertion(s), deletion(s), or a combination thereof) in any one of these SEQ ID NOs that are amenable for modifications as long as the modified TMDs having at least about 80% to the transmembrane domain of a Type I transmembrane receptor and comprising one or more ligand-inducible proteolytic cleavage site, and that the modified TMDs still retain the ability for cleavage at a ligand-inducible proteolytic cleavage site within the transmembrane domain upon binding of a selected ligand to the extracellular binding domain? Particularly, Hudecek et al already highlighted at least the unpredictability in the design and construct of a chimeric antigen receptor (CAR), and given that each new scFv and target molecule defines a unique distance from a tumor cell plasma membrane, the adjustment of CAR spacers is unique to each construct and derived via empirical testing of spacer length variants. Moreover, the instant specification also stated “Particularly, provided herein are synZTE-containing Notch receptors that, surprisingly, retain the ability to transduce signals in response to ligand binding despite that the Notch extracellular subunit (NEC), which includes the negative regulatory region (NRR) is partly or completely-removed” (paragraph [0008]).
Since the prior art before the effective filing date of the present application failed to provide sufficient guidance regarding to the aforementioned issues, it is incumbent upon the present application to do so. Given the state of the prior art, coupled with the lack of sufficient guidance provided by the present application, it would have required undue experimentation for a skilled artisan to make and use the instant invention as claimed broadly.
Accordingly, due to the lack of sufficient guidance provided by the specification regarding to the issues set forth above, the state and unpredictability of the relevant art, and the breadth of the instant claims, it would have required undue experimentation for one skilled in the art to make and use the instantly claimed invention.
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.
Claims 43, 52, 62-63, 66, 69, 73 and 81-83 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.
It is unclear what is encompassed by the limitation “a transmembrane domain having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the transmembrane domain of a Type I transmembrane receptor” for a chimeric polypeptide that is encoded by a recombinant nucleic acid of the instant claims. This is because each member in a family of Type I transmembrane receptors has a different transmembrane domain from that of another member; and thereby it is unclear which particular transmembrane domain of a Type I transmembrane receptor does the limitation refer to? Additionally, there is insufficient antecedent basis for this limitation in the claims because prior to this limitation there is no recitation of any transmembrane domain of a Type I transmembrane receptor. Moreover, there is no recited sequence of any transmembrane domain of a Type I transmembrane receptor as a reference sequence, then how can one determine whether a transmembrane domain having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity as required by the limitation? Clarification is requested because the metes and bounds of the claims are not clearly determined.
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 43, 52, 62-63, 66, 69, 73 and 81-83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 32, 35, 43, 52, 62-63, 66, 69, 73 and 81-83 of copending Application No. 17/995,765 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because a recombinant nucleic acid comprising a nucleotide sequence that encodes the chimeric polypeptide according to claim 1, including the chimeric polypeptide comprising the ZFA having the sequence of SEQ ID NO: 56; a recombinant cell comprising the same recombinant nucleic acid; a cell culture comprising the same recombinant cell; a kit or a pharmaceutical composition comprising the same recombinant nucleic acid and/or the same recombinant cell; a method for making an engineered cell using the same recombinant nucleic acid; and a method for modulating an activity of a target cell in an individual or a method for the treatment of any health condition in an individual using an effective number of the same recombinant cells in copending Application No. 17/995,765 encompass the compositions, methods of making and using the same compositions of the present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusions
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/
Primary Examiner, Art Unit 1631