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 .
DETAILED ACTION
Application Status
This application is a CON of US patent application 17/268,345, filed on 07/25/2024.
Claims 104-123 are currently pending.
The preliminary amendment filed on 07/25/2024, canceling claims 1-103 and adding new claims 104-123 is acknowledged.
Election/Restriction
Applicant's election without traverse of Group I, Claims 104-121, drawn to a genetically engineered T cell, which expresses: a) a glutamic-oxaloacetic transaminase (GOT), which is encoded by an exogenous DNA and b) a chimeric receptor polypeptide comprising (i) an extracellular target binding domain, (ii) a transmembrane domain, and (iii) a cytoplasmic signaling domain in the response filed on 07/20/2026 is acknowledged.
Claims 122-123 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicants request for rejoinder is noted. However, current claims of elected Group I are not allowable at this time. When Group I would be allowable, rejoinder request would be evaluated at that time.
The requirement is still deemed proper and is therefore made FINAL.
Claims 104-121 are present for examination.
Priority
Acknowledgement is made of applicants claim for priority of US patent application 17/268,345, filed on 02/12/2021, now US patent 12077785; and US Provisional applications 62/718579, filed on 08/14/2018, and 62/718,491, filed on 08/14/2018, and International patent application PCT/US2019/046550, filed on 08/14/2019.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 02/03/2025, and 05/15/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner. The signed copies of 1449 are enclosed herewith.
Drawings
Drawings submitted on 07/25/2024 are accepted by the Examiner.
Claim Rejections - 35 USC § 112(a)
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.
A. Written Description
Claims 104-121 are rejected under 35 U.S.C. 112(a), 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 104 is directed to a genetically engineered T cell, which expresses: a) a glutamic-oxaloacetic transaminase (GOT), which is encoded by an exogenous DNA and b) a chimeric receptor polypeptide comprising (i) an extracellular target binding domain, (ii) a transmembrane domain, and (iii) a cytoplasmic signaling domain.
The Court of Appeals for the Federal Circuit has held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).
Thus, Claim 104 is drawn to a genetically engineered T cell, which expresses: a) any glutamic-oxaloacetic transaminase (GOT) gene derived from any unknown sources having no structural feature, which is encoded by any exogenous DNA derived from any unknown sources having no structural feature, and b) any chimeric receptor polypeptides having no structure comprising (i) any extracellular target binding domain having no structure, (ii) any transmembrane domain having no structure, and (iii) any cytoplasmic signaling domain having no structure, i.e., claimed genetically engineered T cell comprises many GOT protein derived from any unknown sources having no structure, and many chimeric receptor polypeptides with unknown extracellular target binding domain, transmembrane domain, and cytoplasmic signaling domain, that encompasses many GOT proteins, and many chimeric receptor polypeptides, and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, i.e. No Structure-Function correlation, which is required to fulfill the Written Description (WD) requirement.
As discussed in the written description guidelines 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 applicant was in possession of the claimed genus. 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.
Furthermore, the genus of genes encoding polypeptides of genetically engineered T cells required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides are adequately described by the disclosure of the structures of prior art. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer, it is difficult to state criteria for successful prediction of function, since function is a vague concept. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Claims are drawn to very broadly a genetically engineered T cell, which expresses: a) any glutamic-oxaloacetic transaminase (GOT) gene derived from any unknown sources having no structural feature, which is encoded by any exogenous DNA derived from any unknown sources having no structural feature, and b) any chimeric receptor polypeptides having no structure comprising (i) any extracellular target binding domain having no structure, (ii) any transmembrane domain having no structure, and (iii) any cytoplasmic signaling domain having no structure, i.e., claimed genetically engineered T cell comprises many GOT protein derived from any unknown sources having no structure, and many chimeric receptor polypeptides with unknown extracellular target binding domain, transmembrane domain, and cytoplasmic signaling domain, that encompasses many GOT proteins, and many chimeric receptor polypeptides, and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of few genetically engineered T cells has been provided, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the genetically engineered T cells expresses: a) glutamic-oxaloacetic transaminase (GOT) gene, which is encoded by exogenous DNA, and b) chimeric receptor polypeptides comprising (i) extracellular target binding domain having no structure, (ii) any transmembrane domain, and (iii) cytoplasmic signaling domain, i.e., claimed genetically engineered T cell comprises many GOT protein and many chimeric receptor polypeptides, within the scope of the claimed genus. The genus of polypeptides in a genetically engineered T cells claimed is a large variable genus including many mutants, variant and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated engineered T cells expressing GOT and chimeric receptor polypeptides within the scope of these claims. The specification discloses the structure of only few representative species of the claimed genus, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed genus. Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Double Patenting Rejection
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. See 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); and 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 104-121 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over at least claims 1-21 of US patent 12077785 B2, patent granted on 09/03/2024, see IDS).
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 104-121, are directed to a genetically engineered T cell, which expresses: a) a glutamic-oxaloacetic transaminase (GOT), which is encoded by an exogenous DNA and b) a chimeric receptor polypeptide comprising (i) an extracellular target binding domain, (ii) a transmembrane domain, and (iii) a cytoplasmic signaling domain, wherein the chimeric receptor polypeptide further comprises a co-stimulatory signaling domain, wherein the co-stimulatory domain is of 4-1BB or CD28, wherein the cytoplasmic signaling domain of (c) is a cytoplasmic domain of CD3ζ or FcεR1γ, wherein the chimeric receptor polypeptide further comprises a hinge domain, which is located at the C-terminus of (a) and the N-terminus of (b), wherein the chimeric receptor polypeptide further comprises a signal peptide at its N-terminus, wherein the chimeric receptor polypeptide is a chimeric antigen receptor (CAR) polypeptide and the extracellular target binding domain thereof comprises a single chain antibody fragment, wherein the CAR polypeptide comprises, from the N-terminus to the C-terminus, (i) the extracellular target binding domain, (ii) a transmembrane domain, (iii) a hinge domain, (iv) a co-stimulatory domain, and (v) a cytoplasmic signaling domain, wherein, wherein the wherein the CAR polypeptide comprises the amino acid sequence of SEQ ID NOs: 104 or 105, wherein the GOT is GOT1 or GOT2, wherein the GOT is GOT2, wherein the chimeric receptor polypeptide is a CAR polypeptide comprising the amino acid sequence of SEQ ID NOs: 104 or 105, wherein in the T cell, the expression of an endogenous T cell receptor, an endogenous major histocompatibility complex, an endogenous beta-2-microglobulin, or a combination thereof has been inhibited or eliminated, wherein the genetically modified T cell comprises a nucleic acid or nucleic acid set, which collectively comprises: (a) a first nucleotide sequence encoding the GOT polypeptide; and (b) a second nucleotide sequence encoding the chimeric receptor polypeptide, wherein the nucleic acid further comprises a third nucleotide sequence located between the first nucleotide sequence and the second nucleotide sequence, wherein the third nucleotide sequence encodes a ribosomal skipping site, an internal ribosome entry site (IRES), or a second promoter, wherein the third nucleotide sequence encodes a ribosomal skipping site, which is a P2A peptide, and a population of immune cells, comprising a plurality of the genetically engineered T cells of claim 104.
The claims 104-121of the US patent 11559603 B2 disclose a genetically engineered hematopoietic cell, which has a modulated Krebs cycle as compared with a native hematopoietic cell of the same hematopoietic cell type; wherein the genetically engineered hematopoietic cell expresses: (i) a Krebs cycle modulating polypeptide, which is glutamic-oxaloacetic transaminase (GOT), isocitrate dehydrogenase (IDH), malate dehydrogenase (MDH), phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1), glutamate dehydrogenase (GDH1), glutamate-pyruvate transaminase 1 (GPT1), or glutaminase (GLS); and (ii) a chimeric receptor polypeptide, which comprises (a) an extracellular target binding domain; (b) a transmembrane domain; and (c) a cytoplasmic signaling domain; and wherein the Krebs cycle modulating polypeptide is encoded by an exogenous nucleic acid; and wherein the transmembrane domain is from a membrane protein selected from the group consisting of CD8α, CD8β, CD137, CD27, CD28, CD34, CD4, FcεR1γ, CD16, CD134, CD32, CD64, CD45, CD5, CD9, CD22, CD37, CD80, CD86, CD40, CD154, VEGFR2, FAS, and FDFR2B, wherein the Krebs cycle modulating polypeptide is GOT, which is GOT1 or GOT2, wherein the chimeric receptor polypeptide is a chimeric receptor antigen (CAR) polypeptide, in which (a) is an extracellular antigen binding domain, wherein the chimeric receptor polypeptide further comprises at least one co-stimulatory signaling domain, wherein the chimeric receptor polypeptide further comprises a hinge domain, which is located at the C-terminus of (a) and the N-terminus of (b); and/or wherein the chimeric receptor polypeptide further comprises a signal peptide at its N-terminus. wherein the extracellular target binding domain of (a) in the CAR polypeptide is a single chain antibody fragment, wherein the at least one co-stimulatory signaling domain is of a co-stimulatory molecule selected from the group consisting of 4-1BB, CD28, CD28LL→GG variant, OX40, ICOS, CD27, GITR, ICOS, HVEM, TIM1, LFA1, and CD2, wherein the at least one co-stimulatory signaling domain is a CD28 co-stimulatory signaling domain or a 4-1BB co-stimulatory signaling domain, wherein the cytoplasmic signaling domain of (c) is a cytoplasmic domain of CD3ζ or FcεR1γ, wherein the hinge domain is of CD28, CD16A, CD8α, or IgG, wherein the chimeric receptor polypeptide is a CAR polypeptide, which comprises (i) a CD28 co-stimulatory domain in combination with a CD28 transmembrane domain, a CD28 hinge domain, or a combination thereof, or (ii) a 4-1BB co-stimulatory domain in combination with a CD8α transmembrane domain, a CD8 hinge domain, or a combination thereof, wherein the CAR polypeptide comprises the amino acid sequence of SEQ ID NOs: 104 or 105, wherein the hematopoietic cell is a hematopoietic stem cell or an immune cell, wherein the hematopoietic cell is the immune cell, which is a T cell in which the expression of an endogenous T cell receptor, an endogenous major histocompatibility complex, an endogenous beta-2-microglobulin, or a combination thereof has been inhibited or eliminated, wherein the hematopoietic cell is an immune cell, which is derived from peripheral blood mononuclear cells (PBMC), hematopoietic stem cells (HSCs), or induced pluripotent stem cells (iPSCs), wherein the hematopoietic cell comprises a nucleic acid or nucleic acid set, which collectively comprises:
(A) a first nucleotide sequence encoding the Krebs cycle metabolite modulating polypeptide; and
(B) a second nucleotide sequence encoding the chimeric receptor polypeptide, wherein the nucleic acid or the nucleic acid set is an RNA molecule or a set of RNA molecules; wherein the nucleic acid or the nucleic acid set is comprised within a vector or a set of vectors, wherein the hematopoietic cell comprises the nucleic acid, which comprises both the first nucleotide sequence and the second nucleotide sequence, wherein the nucleic acid further comprises a third nucleotide sequence located between the first nucleotide sequence and the second nucleotide sequence, wherein the third nucleotide sequence encodes a ribosomal skipping site, an internal ribosome entry site (IRES), or a second promoter, wherein the third nucleotide sequence encodes a ribosomal skipping site, which is a P2A peptide, and a pharmaceutical composition, comprising a genetically engineered hematopoietic cell of claim 1, and a pharmaceutically acceptable carrier.
The above indicated claim(s) of the reference patent while not totally identical to the instant claims, are indeed a product claim of a genetically engineered hematopoietic cell, comprising: wherein the Krebs cycle modulating polypeptide is GOT, which is GOT1 or GOT2, wherein the chimeric receptor polypeptide is a chimeric receptor antigen (CAR) polypeptide, in which (a) is an extracellular antigen binding domain, wherein the chimeric receptor polypeptide further comprises at least one co-stimulatory signaling domain, wherein the chimeric receptor polypeptide further comprises a hinge domain, which is located at the C-terminus of (a) and the N-terminus of (b); and/or wherein the chimeric receptor polypeptide further comprises a signal peptide at its N-terminus. wherein the extracellular target binding domain of (a) in the CAR polypeptide as claimed in the instant claims. The portion of the claims and the specification in the reference patent US 11559603 B2, while drawn to the actual product as claims in the instant application, includes several embodiments that would anticipate the invention claimed in the instant application. Claims of the instant application listed above cannot be considered patentably distinct over claims of the reference patents when there are specifically recited embodiments that would either anticipate to claims 1-21 of the instant application or alternatively render them obvious. Alternatively, claims 1-21 cannot be considered patentably distinct over claims of the reference patent US 11559603 B2, when there is specifically disclosed embodiment in the reference patent that falls within the scope of claims 1-21 of the instant application, i.e. there is substantially overlapping scope between the claimed invention and the teachings of the reference. One having ordinary skill in the art would have been motivated to do so because that embodiment is disclosed as being a preferred embodiment within the claims 1-21 of US patent 11559603 B2,
Note: The present application claims priority as a CON to the parent application 17/268,345 of US patent 11559603 B2, and thus negating safe harbor from non-statutory ODP rejections since the present claims are drawn to a same product claimed invention of a genetically engineered T cells from what was examined in parent. Thus, as discussed above, the a presently claimed a genetically engineered T cells comprising GOT, which is GOT1 or GOT2 and CAR protein molecules is patentably indistinct from and not protected by the safe harbor from, the claim to the GOT, which is GOT1 or GOT2, and CAR protein molecules is patentably indistinct from and not protected by the safe harbor from, the claim to the GOT, which is GOT1 or GOT2, and CAR protein molecules in the parent patent.
Conclusion
Status of the claims:
Claims 1-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Patent Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office (USPTO)
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656
Prosecution Insights