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 .
Election/Restrictions
1. The response filed on June 12, 2026 to the restriction requirement of April 13, 2026 has been received. Applicant has elected for examination the species of a CAR cell with a CD3 zeta chain and a second coding sequence of tEGFR for the method of treating, preventing, or ameliorating a disease in a subject with immunotherapy. Because Applicant did not distinctly and specifically point out any errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)). Claims 34-53 are pending. Claim 51 is withdrawn as being drawn to non-elected species. Claims 34-50 and 52-53 are currently under prosecution as drawn to the elected species.
Priority
2. Application claims the benefit and priority of PCT/GB2022/051003 filed 4/21/2022 which claims the benefit of GB2105684.1 filed 4/21/2021. After review priority has been granted to GB2105684.1 and the effective filing date of 4/21/2021.
Specification
3. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 75-76. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
4. Claim 53 is objected to because of the following informalities: the space between “cell ,and” in the last line, please correct to “cell, and”. Appropriate correction is required.
Claim Interpretation
5. The examiner’s broadest reasonable interpretation of the claims is set forth below.
Claims 36-39, 42-43 and 45 all recite sequence structure with the phrase “a [nucleotide/amino acid] sequence substantially as set out in SEQ ID NO: XX, or a fragment or variant thereof”. Applying the broadest reasonable interpretation of the limitation, a fragment or variant of the sequence allows for any fragment of sequences included in the given sequence and any variants including mutations, deletions, or substitutions.
Applicant has defined the term “substantially” in the specification on page 47 lines 27-31:
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Therefore, a BRI of the above phrase would be any sequence fragments or deletions, additions, substitutions that comprise at least 40% of the original sequence structure cited.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
6. Claims 38-39, 40-42, and 43 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 38, 39, and 43 recites the construct of claim 34, while further reciting “a nucleotide sequence encoding” a CD8a hinge and transmembrane domain, or amino acid sequence or nucleotide sequence of SEQ ID NOs:20, 21, 29, and 30, respectively. It is unclear from the claims how these nucleotide sequences are located in the construct of claim 34, where claim 34 recites a construct comprising a promoter operably linked to a first coding sequence. Are these nucleotide sequences encoding for the promoter region, the first coding sequence, or another coding sequence?
To overcome this rejection, it is suggested to amend claims 38, 39, and 43 to recite the first coding sequence.
Claim 40 recites “more preferably at least two suicide proteins.” The phrase more preferably is indefinite and does not make clear whether the phrase following is a limitation or an option to the claim. For the sake of compact prosecution, the examiner will interpret the phrase as “optionally.”
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.
7. Claims 34-50 and 52-53 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a nucleic acid construct that comprises a first coding sequence which encodes an anti-CD4 chimeric antigen receptor (CAR), wherein the CAR is specific for a CD4 antigen substantially as set out in SEQ ID NO:1. No sequence structure is recited that provides the anti-CD4 CAR function.
Dependent claim 37 recites the first coding sequence comprises a nucleotide sequence encoding an amino acid sequence substantially as set out in (i.e., has at least 40% sequence identity to) SEQ ID NO:6 and/or 8, or a fragment or variant thereof; or the first coding sequence comprises a nucleotide sequence substantially as set out in (i.e., has at least 40% sequence identity to) SEQ ID NO:7 and/or 9, or a fragment or variant thereof.
Claims 40-42 further recites the nucleic acid construct comprising a second coding sequence encoding a suicide protein, truncated epidermal growth factor receptor (tEGFR); or encoding an amino acid sequence substantially as set out in (i.e., has at least 40% sequence identity to) SEQ ID NO:22 represented by a truncated epidermal growth factor receptor (tEGFR), or the construct comprises a nucleic acid sequence substantially as set out in (i.e., has at least 40% sequence identity to) SEQ ID NO:23, or a fragment or variant thereof.
Thus, the claims encompass a nucleic acid construct encoding a genus of CARs that function to bind CD4 and a partial amino acid structure of at least 40% identity to SEQ ID NOs:6 and/or 8, or a fragment or variant thereof; or encompass a nucleic acid construct comprising a nucleotide sequence substantially as set out in (i.e., has at least 40% sequence identity to) SEQ ID NOs:7 and/or 9, or a fragment or variant thereof. The genus of CD4-specific CAR sequences is vast.
The claims further encompass the nucleic acid construct by a second coding sequence encoding a genus of tEGFR suicide proteins and a partial nucleotide sequence of at least 40% of SEQ ID NOs: 23 or the nucleotide sequence that encodes at least 40% of the amino acid sequence of SEQ ID NO: 22, or comprises any fragments of SEQ ID NOs:22 or 23, or any variants of SEQ ID NOs:22 or 23 comprising any mutations and sequence variations. The genus of suicide protein and tEGFR sequences comprised by the construct is vast.
The instant specification discloses one VL and one VH chain that bind to CD4 together, wherein the VL comprises amino acid SEQ ID NO:6, encoded by SEQ ID NO:7; and the VH comprises amino acid SEQ ID NO:8, encoded by SEQ ID NO:9 (see pages 17-18). There is no indication that any alterations can be made to the structure of one of the listed sequences above and still retain binding to CD4, and there is no indication that the CAR functions to bind CD4 by a single VL or single VH region.
The instant specification discloses one tEGFR nucleotide and amino acid sequence structure of SEQ ID NOs: 22 and 23 on pages 25-26 that bind anti-EGFR antibody Cetuximab with no indication of any alterations that could be made to either structure and retain the binding to Cetuximab or any other anti-EGFR antibody.
Thus, the instant specification discloses one anti-CD4 binding domain and describes the complete nucleotide and amino acid structure for the VH and VL regions that function to bind CD4. The specification fails to disclose any alterations that could be made to the sequences of SEQ ID NOs: 6, 7, 8, or 9 and still retain binding to CD4.
The instant specification further discloses one tEGFR polypeptide and describes the complete nucleotide and amino acid sequences of SEQ ID NO: 22 and 23 that function to bind Cetuximab. The specification fails to disclose any alterations that could be made to SEQ ID NOs: 22 or 23 and retain binding to Cetuximab.
To provide adequate written description and evidence of possession of the claimed nucleic acid construct genus, the instant specification can structurally describe representative nucleotide or amino acid sequences that encode binding domain regions that function to bind CD4, or representative nucleotide sequence variants that encode tEGFR proteins that function to bind anti-EGFR antibodies or to act as a suicide protein, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
In this case, the only factor present in the claims are the recitation of an “anti-CD4 CAR” or the recitation of a tEGFR suicide protein and partial sequence structure as stated above. The instant specification fails to describe structural features common to the members of the CAR genus or tEGFR suicide protein genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative variant nucleotide sequences that encode the proteins that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the protein does, rather than what it is. Other than the VH and VL binding domains of SEQ ID NOs: 6, 7, 8, and 9 that bind CD4 and the tEGFR sequences of SEQ ID NOs: 22 and 23 that bind Cetuximab disclosed, the specification fails to provide the VH, VL, or tEGFR nucleotide or amino acid structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of nucleotide or amino acid sequence variants for the genus of nucleic acid constructs that encode proteins that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed nucleic acid constructs encoding an anti-CD4 CAR or a second coding sequence encoding a tEGFR suicide protein.
The claims broadly encompass any nucleic acid construct variants having at least 40% sequence identity to SEQ ID NOs: 6, 7, 8, or 9, or fragments or variants thereof, that function to bind CD4. Applicants have not established any reasonable structure-function correlation with regards to the sequences listed above that can be altered and still maintain CD4 binding function. Given the well-known high level of polymorphism of antigen binding domain sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of nucleic acid constructs encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single exemplary nucleic acid encoding an anti-CD4 CAR comprising SEQ ID NOs: 6, 7, 8, or 9 to the structure of any variants required to bind CD4 as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
The claims broadly encompass any nucleic acid sequence variants encoding at least 40% of SEQ ID NOs: 22 or 23, or fragments or variants thereof, that represent a tEGFR protein functioning as a suicide protein to bind Cetuximab. Applicants have not established any reasonable structure-function correlation with regards to the sequences listed above that can be altered and still maintain binding to Cetuximab. Given the well-known high level of polymorphism of antibody binding sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of sequence variants encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single exemplary nucleic acid encoding tEGFR, SEQ ID NOs: 22 or 23, to the structure of any variants required to function as a suicide protein as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for binding domains that bind CD4 or Cetuximab and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future binding domains or antigens yet to be discovered that may function as claimed. The CD4 antigen or Cetuximab antibody provides no information about the structure of a domain that binds to it.
Given the lack of representative examples to support the full scope of the claimed nucleic acid constructs, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the disclosed sequences that provide CD4 or Cetuximab binding/suicide protein function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of nucleic acid construct variants that encode anti-CD4 CARs that is required to practice the claimed invention. The specification also does not provide an adequate written description of nucleic acid constructs that encode tEGFR variants that bind Cetuximab antibodies and function as a suicide protein that is required to practice the claimed invention.
Examiner Suggestion: Examiner suggests amending claim 34 to recite:
“A nucleic acid construct comprising a promoter operably linked to a first coding sequence, which encodes an anti-CD4 chimeric antigen receptor (CAR), wherein the first coding sequence comprises a nucleotide sequence encoding the amino acid sequence as set forth in SEQ ID NO: 6, and/or wherein the first coding sequence comprises the nucleotide sequence as set forth in SEQ ID NO: 7, and (ii) the first coding sequence comprises a nucleotide sequence encoding the amino acid sequence as set forth in SEQ ID NO: 8 and/or wherein the first coding sequence comprises the nucleotide sequence as set forth in SEQ ID NO: 9.”
Examiner suggests amending claim 42 to recite:
“A construct according to claim 40, wherein: (i) the construct comprises a nucleotide sequence encoding the amino acid sequence forth the nucleotide sequence forth in SEQ ID No: 23.”
8. Claims 48-50 and 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating or ameliorating a disease characterized by CD4+ cell expression in a subject with immunotherapy, does not reasonably provide enablement for preventing any disease or treating or ameliorating a disease not expressing CD4+ in a subject with immunotherapy. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims are drawn to a method of treating, preventing or ameliorating a disease in a subject with immunotherapy by administering to the subject the anti-CD4 CAR-T cell or a pharmaceutical composition including the anti-CD4 CAR-T cell.
The specification discloses in vitro killing assays and intracellular cytokine assays, and in vivo mouse xenograft experiments.
Specifically, the specification demonstrates the anti-CD4 CAR T cells could induce killing against CD4+ T cell population while the CD8+ T cell population remained relatively unaffected, see Figure 2A below.
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The specification also demonstrates the anti-CD4 CAR T cells were able to effectively target CD4+ expressing cell lines, in particular Jurkat and CEM-ss cell lines. However, the anti-CD4 CAR T cells were ineffective against a B cell line that does not express CD4, as demonstrated in Figure 2D below. (See also Example 2).
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The specification further demonstrated the ability of the anti-CD4 CAR T cells to target malignant CD4+ expressing T cells in in vitro assays. Further, in vivo experiments using a xenogeneic mouse model where malignant cells were administered and then the anti-CD4 CAR cells were administered four days later, demonstrating improved survival and delayed tumor progression. (See Examples 3 and 4, also Figures 3, 4).
Relevant art teaches that CARs are recombinant receptors for specific antigens, redirecting the specificity and function of T cells and other immune cells. (Sadelain et al., Cancer Disc., 2013, 3(4):388-398).
One cannot extrapolate the disclosure of the specification to the scope of the claims because the breadth of the claims requires the anti-CD4 CAR cells to prevent any disease but the examples provided in the specification demonstrate the present invention can only effectively treat disease involving CD4+ cells. Further, no examples demonstrated the prevention of a disease state, in vitro and in vivo models of disease were already known to possess the disease prior to the introduction of the anti-CD4 CAR cells, no examples demonstrated the cells being administered and then disease induced after with anti-CD4 CAR cells lessening the effect of the disease. As Sadelain indicated, CAR cells are known in the art to be specific for an antigen and direct the immune cells expressing the CAR protein to the specifically expressed target antigen, in this case CD4.
Reasonable correlation must exist between the scope of the claims and scope of enablement set forth, and it cannot be reasonably predicted that the anti-CD4 CAR T cell will predictably function as claimed.
Therefore, in view of the state of the art, the breadth of the claims, lack of guidance in the specification, and the absence of working examples, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
Examiner suggestion: Examiner suggests amending claim 48 to recite:
“A method of (i) treatingcomprising CD4+ expressing cells in a subject with immunotherapy,…”.
Amend claim 49 to remove “preventing” in line 1.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
9. Claims 34-41, 44, 46, 48-50 and 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ma (US10273280 B2 pub. 2/26/2016).
Regarding claims 34-36, 44, and 46, Ma discloses an expression vector comprising a nucleic acid construct comprising a promoter sequence, including an inducible promoters, constitutive promoters, and specifically human elongation factor -1 alpha, Cytomegalovirus promoter, CAGG promoter, simian virus 40, ubiquitin C, and phosphoglycerokinase (PGK) promoter, operably linked to a first coding sequence, including a CD4 CAR polypeptide. (See Ma, pg. 1 column 2 lines 54-57; also pg. 90 column 2 line 41- pg. 91 column 1 line 20). Ma discloses the expression vector can be expressed through a T cell. (See Ma, pg. 92, column 2 lines 19-23).
Regarding claims 37-39, Ma discloses an embodiment of the expression vector could encode a CD4 CAR represented by the amino acid sequences of SEQ ID NO: 6 and 8 (SEQ ID NO: 13, see alignment below) and further comprising a CD8a hinge and transmembrane domain encoded by the amino acid sequence of SEQ ID NO: 14 and a CD3 zeta chain intracellular signaling domain comprising the amino acid sequence of SEQ ID NO: 20 (SEQ ID NO: 14, see alignment below). (See Ma pg. 94 column 25 lines 48-56).
Regarding claims 40-41 and 52, Ma further discloses the use of suicide proteins with engineered CAR cells including using tEGFR. Ma teaches the method of triggering the tEGFR suicide proteins through the administration of anti-EGFR antibody, Cetuximab. (See Ma, pg. 93 column 24 lines 16-46).
Regarding claims 48-50, Ma teaches that the engineered CAR cells can be used as a method to treat or ameliorate a disease in a subject with immunotherapy including targeting CD4. (See Ma, pg. 94 column 26 lines 57-61). Ma further teaches the method of treating any acute lymphocytic leukemia, various solid and liquid tumors, lymphoma- including peripheral T cell lymphoma. (See Ma, pg. 95 column 28 line54- pg. 96 column 29 line 23).
SEQ ID NO: 6 matches 100% SEQ ID NO: 13 (Ma):
US-15-551-862-13
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 13, US/15551862
Patent No. 10273280
GENERAL INFORMATION
APPLICANT: iCell Gene Therapeutics, LLC
TITLE OF INVENTION: CHIMERIC ANTIGEN RECEPTORS (CARs) HEMATOLOGIC MALIGNANCIES,
TITLE OF INVENTION: COMPOSITIONS AND METHODS OF USE THEREOF
FILE REFERENCE: 2541-2 PCT/US
CURRENT APPLICATION NUMBER: US/15/551,862
CURRENT FILING DATE: 2017-08-17
PRIOR APPLICATION NUMBER: PCT/US2016/019953
PRIOR FILING DATE: 2016-02-26
PRIOR APPLICATION NUMBER: 62/121,842
PRIOR FILING DATE: 2015-02-27
NUMBER OF SEQ ID NOS: 38
SEQ ID NO 13
LENGTH: 535
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synethic sequence
Query Match 100.0%; Score 585; Length 535;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 22 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTR 81
Qy 61 ESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYRTFGGGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 82 ESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYRTFGGGTKLEIK 133
SEQ ID NO: 8 matches 100% SEQ ID NO: 13 (Ma):
US-15-551-862-13
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 13, US/15551862
Patent No. 10273280
GENERAL INFORMATION
APPLICANT: iCell Gene Therapeutics, LLC
TITLE OF INVENTION: CHIMERIC ANTIGEN RECEPTORS (CARs) HEMATOLOGIC MALIGNANCIES,
TITLE OF INVENTION: COMPOSITIONS AND METHODS OF USE THEREOF
FILE REFERENCE: 2541-2 PCT/US
CURRENT APPLICATION NUMBER: US/15/551,862
CURRENT FILING DATE: 2017-08-17
PRIOR APPLICATION NUMBER: PCT/US2016/019953
PRIOR FILING DATE: 2016-02-26
PRIOR APPLICATION NUMBER: 62/121,842
PRIOR FILING DATE: 2015-02-27
NUMBER OF SEQ ID NOS: 38
SEQ ID NO 13
LENGTH: 535
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synethic sequence
Query Match 100.0%; Score 657; Length 535;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 149 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDY 208
Qy 61 DEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 209 DEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTV 268
Qy 121 SS 122
||
Db 269 SS 270
SEQ ID NO: 14 matches 95.8% in SEQ ID NO: 14 (Ma):
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470
697
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SEQ ID NO: 20 matches 99.1% in SEQ ID NO: 14 (Ma):
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467
673
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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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
10. Claims 34-43, 45, 47, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Ma (US10273280 B2 pub. 2/26/2016) in view of Suri (WO 2019/241315 A1 pub. 12/19/2019).
Ma discloses the limitations of claims 34-41, 44, 46, 48-50, and 52 as discussed above.
Ma does not disclose a nucleic acid construct encoding the tEGFR protein comprising the amino acid sequence of SEQ ID NO: 22, the construct encoding an amino acid sequence of SEQ ID NO: 29, or the expression vector comprising a nucleic acid sequence comprising substantially as set out in SEQ ID NO: 33. Ma does not disclose a pharmaceutical composition comprising a T-cell expressing the nucleic acid construct and a process for making the pharmaceutical composition.
Suri teaches a polynucleotide encoding a CAR sequence being introduced into a T cell through a vector which comprises a promoter, including PGK of the amino acid sequence of SEQ ID NO: 3 (SEQ ID NO: 338, see alignment below), operably linked to a coding sequence that encodes a CAR sequence for a specific antigen, including CD4 and the amino acid sequence of SEQ ID NOs: 6 and 8 (SEQ ID NO: 7636, see alignment below). (See Suri, pgs. 140 [0311], 149 [0342], 225 [0527], 230 [0555]). Suri discloses the CAR nucleic acid sequence can also express a suicide protein of tEGFR comprising the amino acid sequence of SEQ ID NO: 22 (See Suri, pgs. 203-204 [0428], [0435], also SEQ ID NO: 7402, see alignment below). Suri discloses an amino acid sequence of SEQ ID NO: 29 (SEQ ID NO: 7452, see alignment below). Suri also discloses a process of making a pharmaceutical composition by combining a therapeutically effective amount of the CAR cell and a pharmaceutically acceptable excipient. (See Suri, pg. 227 [0539]-[0540]).
Regarding claim 45, the nucleotide sequence of the expression vector comprising SEQ ID NO: 33 is not disclosed by either Ma or Suri. However, the elements of a PGK promoter of SEQ ID NO:3 and the amino acid sequences of the functional elements of the coding sequence for an anti-CD4 CAR are disclosed by both Ma and Suri. Since it is obvious for a person of ordinary skill in the art to know that an amino acid sequence encodes for nucleotide sequence structure and the functional elements required for the nucleotide construct of claim 34 are disclosed by Suri, SEQ ID NO: 33 does not overcome the obviousness rejection.
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to combine the nucleic acid CAR of Ma with the teachings of Suri for the present claimed invention. It would have been obvious because both Ma and Suri disclose anti-CD4 CAR binding domains comprising the same amino acid sequence structure, Suri’s teachings expand on the invention of Ma and teach traditional known elements of CAR cell technology including known CD8a hinge and transmembrane and CD3 zeta intracellular signaling domains, and providing pharmaceutical compositions using therapeutically effective amounts of CAR T cells is well known in the art. Therefore, a person of ordinary skill in the art would have had a reasonable expectation of success at combining the anti-CD4 CAR T cell of Ma with the teachings of Suri to produce the anti-CD4 CAR T cell with a tEGFR suicide protein.
SEQ ID NO: 3 is 99.7%% identical to SEQ ID NO: 338 (Suri):
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646
673
media_image6.png
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SEQ ID NO: 6 is 100% identical to SEQ ID NO: 7636 (Suri):
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
46 585 100.0 535 BDE27200 -- 6 Engineered chimeric antigen receptor CD4CAR protein, SEQ ID 13.
ALIGNMENT:
Query Match 100.0%; Score 585; Length 535;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 22 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTR 81
Qy 61 ESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYRTFGGGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 82 ESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYRTFGGGTKLEIK 133
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7636; 406pp; English.
SEQ ID NO: 8 is 100% identical to SEQ ID NO: 7636 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7636; 406pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
50 657 100.0 535 BDE27200 -- 6 Engineered chimeric antigen receptor CD4CAR protein, SEQ ID 13.
ALIGNMENT:
Query Match 100.0%; Score 657; Length 535;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 149 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDY 208
Qy 61 DEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 209 DEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTV 268
Qy 121 SS 122
||
Db 269 SS 270
SEQ ID NO: 22 is 100%% identical to SEQ ID NO: 7402 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7402; 406pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
95 1958 100.0 838 BBD40613 -- 8 Leader_R11-Hinge-CD28tm/41BB-Z-T2A-tEGFR fusion protein, SEQ 48.
ALIGNMENT:
Query Match 100.0%; Score 1958; Length 838;
Best Local Similarity 100.0%;
Matches 357; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLLVTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 482 MLLLVTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHI 541
Qy 61 LPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 542 LPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTK 601
Qy 121 QHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKII 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 602 QHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKII 661
Qy 181 SNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 662 SNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVE 721
Qy 241 NSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 722 NSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYA 781
Qy 301 DAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 357
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 782 DAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 838
SEQ ID NO: 29 is 51.8% identical to SEQ ID NO: 7452 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7452; 406pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
58 3817 51.8 1133 BAS65488 -- 5 Bispecific chimeric antigen receptor (CAR) protein, SEQ ID 12.
ALIGNMENT:
Query Match 51.8%; Score 3817; Length 1133;
Best Local Similarity 64.3%;
Matches 767; Conservative 33; Mismatches 65; Indels 328; Gaps 15;
Qy 5 TLLLWVL----LLWVPGSTGDDIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYL 60
:||| | | :| || |||: ||: |||:|||::|::|| : ||
Db 7 SLLLCELPHPAFLLIP-----DIQMTQTTSSLSASLGDRVTISCRASQDI------SKYL 55
Qy 61 AWYQQKPGQSPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYS 120
|||||| : ||||| | |||| ||||||||||::||||::: ||:| |:||| :
Db 56 NWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNT 115
Qy 121 Y-RTFGGGTKLEIKG---GGGSGGGG---------------------------------- 142
|||||||||| | | | | |
Db 116 LPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVS 175
Qy 143 ------------------------------------------------------------ 142
Db 176 LPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTD 235
Qy 143 -------------------------------SGGGGSQVQLQQSGPEVVKPGASVKMSCK 171
||||||:||||||| |:||||||||||||
Db 236 DTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGGGGSEVQLQQSGAELVKPGASVKMSCK 295
Qy 172 ASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMEL 231
||||||||| :|||:| |||||:||| | | | | |::|||||||||:| |:|||||:|
Db 296 ASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQL 355
Qy 232 SSLRSEDTAVYYCAREKDNYATGAW-FAYWGQGTLVTVSSA------------------- 271
||| |||:| ||||| : | : | | || || |||||
Db 356 SSLTSEDSADYYCAR-SNYYGSSYWFFDVWGAGTTVTVSSGSTSGGGSGGGSGGGGSSDI 414
Qy 272 ---------------------------------------------------AAFVPV--- 277
|: ||
Db 415 VLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFS 474
Qy 278 -----------------------------FLP-----------------------AKPTT 285
| | ||||
Db 475 GSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKESKYGPPCPPCPKPTT 534
Qy 286 TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLS 345
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 535 TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLS 594
Qy 346 LVITLYCNHRNRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRFSVVKRG 405
|||| |||
Db 595 LVIT-----------------------------------------------------KRG 601
Qy 406 RKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLY 465
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 602 RKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLY 661
Qy 466 NELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR 525
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 662 NELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR 721
Qy 526 RGKGHDGLYQGLSTATKDTYDALHMQALPPR--GSGATNFSLLKQAGDVEENPGP-MLLL 582
||||||||||||||||||||||||||||||| | | ||| ||||||||| ||||
Db 722 RGKGHDGLYQGLSTATKDTYDALHMQALPPRLEGGGEGRGSLL-TCGDVEENPGPRMLLL 780
Qy 583 VTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVA 642
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVA 840
Qy 643 FRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQ 702
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 FRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQ 900
Qy 703 FSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRG 762
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 FSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRG 960
Qy 763 ENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSEC 822
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSEC 1020
Qy 823 IQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGH 882
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 IQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGH 1080
Qy 883 VCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 935
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 VCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 1133
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.
11. Claims 34-50 and 52-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-21, 24, 27, 29-30 and 32-35 of copending Application No. 18287542 (Hereinafter App. ‘542) in view of Suri (WO 2019/241315 A1 pub. 12/19/2019) and Wang (Bioscience Reports, 2020, 40:BSR20202962).
App. ‘542 claims a mucosal-associated invariant T (MAIT) cell transduced with a nucleic acid encoding a CAR construct which targets a CD4 antigen which comprises an amino acid sequence of SEQ ID NO: 1 and another coding sequence for tEGFR represented by the amino acid sequence of SEQ ID NO: 22 and a nucleotide sequence of SEQ ID NO: 23 which are 100% identical to the instant SEQ ID NOs: 22 and 23 (See alignments below). App. ‘542 also claims a method comprising triggering a sequence encoding a suicide protein, optionally wherein the method comprises administering, to the subject, an anti-EGFR antibody and/or a caspase-inducible drug (CID).
App. ‘542 claims a pharmaceutical composition comprising the CAR-MAIT cell and a pharmaceutically acceptable excipient and a process for making the pharmaceutical composition by combining a therapeutically effective amount of the anti-CD4 CAR-MAIT with a pharmaceutically acceptable excipient.
App. ‘542 claims a method for treating, preventing, or ameliorating a disease in a subject with immunotherapy, a T cell malignancy, wherein the T cell malignancy is a PTCL including Adult T-Cell Acute Lymphoblastic Lymphoma or Leukaemia (ATL); Enteropathy-Associated Lymphoma; Hepatosplenic Lymphoma; Subcutaneous Panniculitis-Like Lymphoma (SPTCL); Precursor T-Cell Acute Lymphoblastic Lymphoma or Leukaemia; and Angioimmunoblastic T-cell lymphoma (AITL); or CTCL is a CTCL subtype selected from a group consisting of: Mycosis fungoides (MF); Sezary syndrome (SS); and CD4+ small medium pleomorphic T-cell lymphoproliferative disorder.
App. ‘542 does not claim the nucleic acid construct being introduced to the MAIT cell through a vector and comprising a promoter and a first coding sequence that encodes an anti-CD4 chimeric antigen receptor that further comprises a CD8a hinge and transmembrane structure domain, and the nucleotide sequences of SEQ ID NOs: 7, 9, 21, 30, and 33 or the nucleotide sequences encoding the amino acid sequences of SEQ ID NO: 6, 8, 20, and 29.
Suri teaches a polynucleotide encoding a CAR sequence being introduced into a T cell through a vector which comprises a promoter, including PGK of the amino acid sequence of SEQ ID NO: 3 (SEQ ID NO: 338, see alignment below), operably linked to a coding sequence that encodes a CAR sequence for a specific antigen, including CD4 and the amino acid sequence of SEQ ID NOs: 6 and 8 (SEQ ID NO: 7636, see alignment below). (See Suri, pgs. 140 [0311], 149 [0342], 225 [0527], 230 [0555]). Suri teaches CD8a hinge and transmembrane domains are regularly used in CAR sequences and disclose amino acid sequence of SEQ ID NO: 14 (SEQ ID NO: 6711, see alignment below) and CD3zeta is regularly used as a intracellular signaling domain and discloses the amino acid sequence of SEQ ID NO: 20 (SEQ ID NO: 6627, see alignment below). (See Suri, pgs. 144 [0324], 145 [0330], 145-146 [0331]-[0334]). Suri discloses 51.8% of the amino acid sequence of SEQ ID NO: 29. (SEQ ID NO: 7452, see alignment below).
Suri does not disclose the nucleotide sequences of SEQ ID NOs: 7, 9, 21, and 30. However because Suri discloses the amino acid sequences of the corresponding nucleotide sequences it would be obvious to determine the nucleotide sequences from the amino acid sequence. In reference to the nucleotide sequence of SEQ ID NO: 33, App. ‘542 and Suri disclose all of the functional amino acid sequence structure of the encoded nucleotide. Therefore, the nucleotide sequences of SEQ ID NOs: 7, 9, 21, 30, and 33 are obvious over the disclosure of App. ‘542 and the teachings of Suri.
Suri does not disclose the expression of a vector through a MAIT cell to produce a MAIT CAR cell.
Wang teaches that MAIT cells are an unconventional population of T cells that express MHC class I-related (MR1) which is a MHC-like molecule that can recognize peptide antigens along with other antigens. (See Wang, pg. 1). Wang teaches that MR1 T cells can target and kill many kinds of cancer cells but not healthy cells using a single TCR clone, providing an advantage over traditional CAR and TCR T cell immunotherapy that require different targets for various cancers. (See Wang, pg. 6).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to combine the invention of App. ‘542 with the teachings of Suri and Wang to produce the invention of the instant application. It would have been obvious because Suri discloses the amino acid sequences of the CD4 binding domains, the transmembrane domain, the hinge region, and the intracellular signaling domains, CD8a transmembrane and hinge regions and CD3 zeta chains and Suri teaches these are known used elements of CAR technologies, and Wang teaches that MAIT T cells provide an advantage over traditional CAR T cells to express fewer target domains but effect a broader range of cancers. It would have a reasonable expectation of success because the functional amino acid sequences are known in the art and have been used successfully in other CAR T cells and Wang teaches that CAR MAIT cells are expected to have significant advantages over traditional CAR T cells. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to combine the CAR MAIT cell of App. ‘542 and the teachings of Suri and Wang for the present claimed invention.
This is a provisional nonstatutory double patenting rejection.
SEQ ID NO: 1 is 100% identical to SEQ ID NO: 1 (App. ‘542):
US-18-287-542-1
Filing date in PALM: 2023-10-19
Sequence 1, US/18287542
Publication No. US20240207312A1
GENERAL INFORMATION
APPLICANT: Imperial College Innovations Limited
TITLE OF INVENTION: Chimeric antigen receptor (CAR)-T cells
FILE REFERENCE: 100915PCT1
CURRENT APPLICATION NUMBER: US/18/287,542
CURRENT FILING DATE: 2023-10-19
PRIOR APPLICATION NUMBER: 2105682.5
PRIOR FILING DATE: 2021-04-21
NUMBER OF SEQ ID NOS: 36
SEQ ID NO 1
LENGTH: 458
TYPE: PRT
ORGANISM: Homo sapiens
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 2364 100.0 458 US-10-103-597A-39 2002-03-21 214 Screening Methods
ALIGNMENT:
Query Match 100.0%; Score 2364; Length 458;
Best Local Similarity 100.0%;
Matches 458; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNRGVPFRHLLLVLQLALLPAATQGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNRGVPFRHLLLVLQLALLPAATQGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIK 60
Qy 61 ILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQL 120
Qy 121 LVFGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGGKTLSVSQLELQDSG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LVFGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGGKTLSVSQLELQDSG 180
Qy 181 TWTCTVLQNQKKVEFKIDIVVLAFQKASSIVYKKEGEQVEFSFPLAFTVEKLTGSGELWW 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TWTCTVLQNQKKVEFKIDIVVLAFQKASSIVYKKEGEQVEFSFPLAFTVEKLTGSGELWW 240
Qy 241 QAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 QAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLA 300
Qy 301 LEAKTGKLHQEVNLVVMRATQLQKNLTCEVWGPTSPKLMLSLKLENKEAKVSKREKAVWV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LEAKTGKLHQEVNLVVMRATQLQKNLTCEVWGPTSPKLMLSLKLENKEAKVSKREKAVWV 360
Qy 361 LNPEAGMWQCLLSDSGQVLLESNIKVLPTWSTPVQPMALIVLGGVAGLLLFIGLGIFFCV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LNPEAGMWQCLLSDSGQVLLESNIKVLPTWSTPVQPMALIVLGGVAGLLLFIGLGIFFCV 420
Qy 421 RCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI 458
||||||||||||||||||||||||||||||||||||||
Db 421 RCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI 458
SEQ ID NO: 22 is 100% identical to SEQ ID NO: 22 (App. ‘542):
US-18-287-542-22
Filing date in PALM: 2023-10-19
Sequence 22, US/18287542
Publication No. US20240207312A1
GENERAL INFORMATION
APPLICANT: Imperial College Innovations Limited
TITLE OF INVENTION: Chimeric antigen receptor (CAR)-T cells
FILE REFERENCE: 100915PCT1
CURRENT APPLICATION NUMBER: US/18/287,542
CURRENT FILING DATE: 2023-10-19
PRIOR APPLICATION NUMBER: 2105682.5
PRIOR FILING DATE: 2021-04-21
NUMBER OF SEQ ID NOS: 36
SEQ ID NO 22
LENGTH: 357
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Truncated EGFR
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 1958 100.0 357 US-13-463-247-3 2012-05-03 245 TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRANSDUCED T CELL SELECT
ALIGNMENT:
Query Match 100.0%; Score 1958; Length 357;
Best Local Similarity 100.0%;
Matches 357; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLLVTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLLVTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHI 60
Qy 61 LPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTK 120
Qy 121 QHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKII 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKII 180
Qy 181 SNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVE 240
Qy 241 NSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 NSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYA 300
Qy 301 DAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 357
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 357
SEQ ID NO: 23 is 100% identical to SEQ ID NO: 23 (App. ‘542):
US-18-287-542-23
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 23, US/18287542
Publication No. US20240207312A1
GENERAL INFORMATION
APPLICANT: Imperial College Innovations Limited
TITLE OF INVENTION: Chimeric antigen receptor (CAR)-T cells
FILE REFERENCE: 100915PCT1
CURRENT APPLICATION NUMBER: US/18/287,542
CURRENT FILING DATE: 2023-10-19
PRIOR APPLICATION NUMBER: 2105682.5
PRIOR FILING DATE: 2021-04-21
NUMBER OF SEQ ID NOS: 36
SEQ ID NO 23
LENGTH: 1071
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Truncated EGFR
Query Match 100.0%; Score 1071; Length 1071;
Best Local Similarity 100.0%;
Matches 1071; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGCTTCTCCTGGTGACAAGCCTTCTGCTCTGTGAGTTACCACACCCAGCATTCCTCCTG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGCTTCTCCTGGTGACAAGCCTTCTGCTCTGTGAGTTACCACACCCAGCATTCCTCCTG 60
Qy 61 ATCCCACGCAAAGTGTGTAACGGAATAGGTATTGGTGAATTTAAAGACTCACTCTCCATA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ATCCCACGCAAAGTGTGTAACGGAATAGGTATTGGTGAATTTAAAGACTCACTCTCCATA 120
Qy 121 AATGCTACGAATATTAAACACTTCAAAAACTGCACCTCCATCAGTGGCGATCTCCACATC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AATGCTACGAATATTAAACACTTCAAAAACTGCACCTCCATCAGTGGCGATCTCCACATC 180
Qy 181 CTGCCGGTGGCATTTAGGGGTGACTCCTTCACACATACTCCTCCTCTGGATCCACAGGAA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CTGCCGGTGGCATTTAGGGGTGACTCCTTCACACATACTCCTCCTCTGGATCCACAGGAA 240
Qy 241 CTGGATATTCTGAAAACCGTAAAGGAAATCACAGGGTTTTTGCTGATTCAGGCTTGGCCT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CTGGATATTCTGAAAACCGTAAAGGAAATCACAGGGTTTTTGCTGATTCAGGCTTGGCCT 300
Qy 301 GAAAACAGGACGGACCTCCATGCCTTTGAGAACCTAGAAATCATACGCGGCAGGACCAAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GAAAACAGGACGGACCTCCATGCCTTTGAGAACCTAGAAATCATACGCGGCAGGACCAAG 360
Qy 361 CAACATGGTCAGTTTTCTCTTGCAGTCGTCAGCCTGAACATAACATCCTTGGGATTACGC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CAACATGGTCAGTTTTCTCTTGCAGTCGTCAGCCTGAACATAACATCCTTGGGATTACGC 420
Qy 421 TCCCTCAAGGAGATAAGTGATGGAGATGTGATAATTTCAGGAAACAAAAATTTGTGCTAT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 TCCCTCAAGGAGATAAGTGATGGAGATGTGATAATTTCAGGAAACAAAAATTTGTGCTAT 480
Qy 481 GCAAATACAATAAACTGGAAAAAACTGTTTGGGACCTCCGGTCAGAAAACCAAAATTATA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GCAAATACAATAAACTGGAAAAAACTGTTTGGGACCTCCGGTCAGAAAACCAAAATTATA 540
Qy 541 AGCAACAGAGGTGAAAACAGCTGCAAGGCCACAGGCCAGGTCTGCCATGCCTTGTGCTCC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AGCAACAGAGGTGAAAACAGCTGCAAGGCCACAGGCCAGGTCTGCCATGCCTTGTGCTCC 600
Qy 601 CCCGAGGGCTGCTGGGGCCCGGAACCCAGGGACTGCGTCTCTTGCCGGAATGTCAGCCGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CCCGAGGGCTGCTGGGGCCCGGAACCCAGGGACTGCGTCTCTTGCCGGAATGTCAGCCGA 660
Qy 661 GGCAGGGAATGCGTGGACAAGTGCAACCTTCTGGAGGGTGAGCCAAGGGAGTTTGTGGAG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GGCAGGGAATGCGTGGACAAGTGCAACCTTCTGGAGGGTGAGCCAAGGGAGTTTGTGGAG 720
Qy 721 AACTCTGAGTGCATACAGTGCCACCCAGAGTGCCTGCCTCAGGCCATGAACATCACCTGC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 AACTCTGAGTGCATACAGTGCCACCCAGAGTGCCTGCCTCAGGCCATGAACATCACCTGC 780
Qy 781 ACAGGACGGGGACCAGACAACTGTATCCAGTGTGCCCACTACATTGACGGCCCCCACTGC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 ACAGGACGGGGACCAGACAACTGTATCCAGTGTGCCCACTACATTGACGGCCCCCACTGC 840
Qy 841 GTCAAGACCTGCCCGGCAGGAGTCATGGGAGAAAACAACACCCTGGTCTGGAAGTACGCA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GTCAAGACCTGCCCGGCAGGAGTCATGGGAGAAAACAACACCCTGGTCTGGAAGTACGCA 900
Qy 901 GACGCCGGCCATGTGTGCCACCTGTGCCATCCAAACTGCACCTACGGATGCACTGGGCCA 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GACGCCGGCCATGTGTGCCACCTGTGCCATCCAAACTGCACCTACGGATGCACTGGGCCA 960
Qy 961 GGTCTTGAAGGCTGTCCAACGAATGGGCCTAAGATCCCGTCCATCGCCACTGGGATGGTG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GGTCTTGAAGGCTGTCCAACGAATGGGCCTAAGATCCCGTCCATCGCCACTGGGATGGTG 1020
Qy 1021 GGGGCCCTCCTCTTGCTGCTGGTGGTGGCCCTGGGGATCGGCCTCTTCATG 1071
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GGGGCCCTCCTCTTGCTGCTGGTGGTGGCCCTGGGGATCGGCCTCTTCATG 1071
SEQ ID NO: 3 is 99.7%% identical to SEQ ID NO: 338 (Suri):
PNG
media_image6.png
646
673
media_image6.png
Greyscale
SEQ ID NO: 6 is 100% identical to SEQ ID NO: 7636 (Suri):
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
46 585 100.0 535 BDE27200 -- 6 Engineered chimeric antigen receptor CD4CAR protein, SEQ ID 13.
ALIGNMENT:
Query Match 100.0%; Score 585; Length 535;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 22 DIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTR 81
Qy 61 ESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYRTFGGGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 82 ESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYRTFGGGTKLEIK 133
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7636; 406pp; English.
SEQ ID NO: 8 is 100% identical to SEQ ID NO: 7636 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7636; 406pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
50 657 100.0 535 BDE27200 -- 6 Engineered chimeric antigen receptor CD4CAR protein, SEQ ID 13.
ALIGNMENT:
Query Match 100.0%; Score 657; Length 535;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 149 QVQLQQSGPEVVKPGASVKMSCKASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDY 208
Qy 61 DEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 209 DEKFKGKATLTSDTSTSTAYMELSSLRSEDTAVYYCAREKDNYATGAWFAYWGQGTLVTV 268
Qy 121 SS 122
||
Db 269 SS 270
SEQ ID NO: 14 is 100% identical to SEQ ID NO: 6711 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 6711; 406pp; English.
XX
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 452 100.0 83 AZG99713 -- 73 Human CD8 extracellular hinge sequence, SEQ ID 3.
ALIGNMENT:
Query Match 100.0%; Score 452; Length 83;
Best Local Similarity 100.0%;
Matches 83; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWA 60
Qy 61 PLAGTCGVLLLSLVITLYCNHRN 83
|||||||||||||||||||||||
Db 61 PLAGTCGVLLLSLVITLYCNHRN 83
SEQ ID NO: 20 is 100% identical to SEQ ID NO: 6627 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 6627; 406pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 593 100.0 112 ADL67239 -- 2672 Human CD3 zeta chain intracellular domain.
ALIGNMENT:
Query Match 100.0%; Score 593; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
Qy 61 ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
SEQ ID NO: 29 is 51.8% identical to SEQ ID NO: 7452 (Suri):
WO2019241315-A1.
XX
CC PD 19-DEC-2019.
XX
CC PF 12-JUN-2019; 2019WO-US036654.
XX
PR 12-JUN-2018; 2018US-0683972P.
PR 06-NOV-2018; 2018US-0756124P.
PR 11-DEC-2018; 2018US-0777893P.
PR 18-APR-2019; 2019US-0835545P.
XX
CC PA (OBSI-) OBSIDIAN THERAPEUTICS INC.
XX
CC PI Suri V, Richardson C, Dolinski B, Kulkarni A, Inniss MC, Sun D;
CC PI Li DJ, Olinger GY, Heller SF, Gori JL, Delabarre B;
XX
DR WPI; 2019-A6203A/002.
XX
CC PT Effector module comprises a stimulus response element (SRE), where the
CC PT SRE is a DD, comprising one mutation relative to cGMP-specific 3',5'-
CC PT cyclic phosphodiesterase, and one payload, which is attached, appended or
CC PT associated with the SRE.
XX
CC PS Disclosure; SEQ ID NO 7452; 406pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
58 3817 51.8 1133 BAS65488 -- 5 Bispecific chimeric antigen receptor (CAR) protein, SEQ ID 12.
ALIGNMENT:
Query Match 51.8%; Score 3817; Length 1133;
Best Local Similarity 64.3%;
Matches 767; Conservative 33; Mismatches 65; Indels 328; Gaps 15;
Qy 5 TLLLWVL----LLWVPGSTGDDIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKNYL 60
:||| | | :| || |||: ||: |||:|||::|::|| : ||
Db 7 SLLLCELPHPAFLLIP-----DIQMTQTTSSLSASLGDRVTISCRASQDI------SKYL 55
Qy 61 AWYQQKPGQSPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYS 120
|||||| : ||||| | |||| ||||||||||::||||::: ||:| |:||| :
Db 56 NWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNT 115
Qy 121 Y-RTFGGGTKLEIKG---GGGSGGGG---------------------------------- 142
|||||||||| | | | | |
Db 116 LPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVS 175
Qy 143 ------------------------------------------------------------ 142
Db 176 LPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTD 235
Qy 143 -------------------------------SGGGGSQVQLQQSGPEVVKPGASVKMSCK 171
||||||:||||||| |:||||||||||||
Db 236 DTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGGGGSEVQLQQSGAELVKPGASVKMSCK 295
Qy 172 ASGYTFTSYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMEL 231
||||||||| :|||:| |||||:||| | | | | |::|||||||||:| |:|||||:|
Db 296 ASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQL 355
Qy 232 SSLRSEDTAVYYCAREKDNYATGAW-FAYWGQGTLVTVSSA------------------- 271
||| |||:| ||||| : | : | | || || |||||
Db 356 SSLTSEDSADYYCAR-SNYYGSSYWFFDVWGAGTTVTVSSGSTSGGGSGGGSGGGGSSDI 414
Qy 272 ---------------------------------------------------AAFVPV--- 277
|: ||
Db 415 VLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFS 474
Qy 278 -----------------------------FLP-----------------------AKPTT 285
| | ||||
Db 475 GSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKESKYGPPCPPCPKPTT 534
Qy 286 TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLS 345
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 535 TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLS 594
Qy 346 LVITLYCNHRNRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRFSVVKRG 405
|||| |||
Db 595 LVIT-----------------------------------------------------KRG 601
Qy 406 RKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLY 465
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 602 RKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLY 661
Qy 466 NELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR 525
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 662 NELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR 721
Qy 526 RGKGHDGLYQGLSTATKDTYDALHMQALPPR--GSGATNFSLLKQAGDVEENPGP-MLLL 582
||||||||||||||||||||||||||||||| | | ||| ||||||||| ||||
Db 722 RGKGHDGLYQGLSTATKDTYDALHMQALPPRLEGGGEGRGSLL-TCGDVEENPGPRMLLL 780
Qy 583 VTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVA 642
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VTSLLLCELPHPAFLLIPRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVA 840
Qy 643 FRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQ 702
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 FRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQ 900
Qy 703 FSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRG 762
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 FSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRG 960
Qy 763 ENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSEC 822
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSEC 1020
Qy 823 IQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGH 882
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 IQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGH 1080
Qy 883 VCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 935
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 VCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM 1133
Conclusion
12. Claims 34-50 and 52-53 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
Prosecution Insights