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
Response to Election/Restrictions
Applicant’s election with traverse of the following in response to election of species requirement is acknowledged:
“a CD19-specific chimeric antigen receptor” (of SEQ ID 1208) for “Chimeric antigen receptor”,
“a fusion protein comprising the extracellular domain (ECD) of CD19 fused to the luciferase reporter NamoLuc (NLuc) for “fusion protein”, and
“T-cells” for “a cell expressing the CAR”.
Applicant identified claims 1-11, 13-16 and 18-20 read on the elected species.
Applicant argued that the recited species share a common structure, and the pending claims are linked by allowable generic claim.
The above arguments have fully been considered but are not found persuasive because no generic claims are found to be allowable and contrary to Applicant’s assertion, the fusion proteins with the distinct types of extracellular domains (see claim 9) are structurally and functionally distinct and they don’t show common utility. As for example, a fusion protein with CD19 antigen is of distinct property from a fusion protein having EPCAM and are of distinct utility. Accordingly, the restriction requirement is deemed proper and is made FINAL.
Examiner searched prior arts with the scope of the elected species and found arts that renders the claimed composition and method obvious with the scope of the elected species and therefore, claims 12 and 17 and all other non-elected species of the claims are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions. See MPEP 803.02. Applicants preserve their right to file a divisional on the non-elected subject matter.
Claims 1-11, 13-16 and 18-20 are examined on merits in this office action.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-11, 13-16 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira et al (J. Translational Medicine 2013; Cite # 5 in the IDS filed 8/14/2023) in view of Venisnik et al (Mol. Imaging Biol. 2007; Cite # 14 in the IDS filed 8/14/2023) and Luker et al (Biotechniques 2009; Cite # 8 in the IDS filed 8/14/2023).
Regarding claims 1-2, 6, 8-11, 13 and 19-20, Oliveira teaches detection of expression of chimeric antigen receptor (ani-CD19 chimeric antigen receptors) (Abstract). Oliveira teaches expression of CARs in T-lymphocytes (Abstract; page 3, “Flow Cytometry”). Oliveira discloses specific reagent for the detection of ani-CD19 CAR expression wherein the specific reagent comprises fusion protein comprising CD19 extracellular domains (i.e. an antigen targeted by the CAR) and an Fc region of human 1gG1 (CD19slg) (Abstract). Oliveira teaches detection of CAR expression in clinical sample from a subject (Abstract; page 2, 2nd col.). Oliveira discloses conjugating the fusion protein with a fluorophore (Alexa Fluor 488) for detection of CD-19 specific CAR expression (page 6; “see “Flow cytometry staining using fusion proteins”).
Oliveira as described above discloses fusion protein comprising CD19 antigen having detectable molecules as a probe for detection of cells expressing CD19-specific CAR, but however, does not disclose other detectable molecules conjugated to or fused with the fusion protein comprising CD19 antigen.
Venisnik teaches fusion of Gaussia luciferase to an engineered anti-carcinoembrionic antigen (CEA) antibody fragment for detection of cells expressing carcinoembryonic antigen (Abstract). Venisnik teaches various luciferase (Introduction) but teaches that Gluc (Gaussia luciferase) is advantageous for its enhanced brightness and stability over other luciferases and thus is very useful as reporter for fusion with various binding partners (discussion).
Luker teaches detection of expression of CXCR4 and CXCR7 receptors utilizing fusion construct of CXCL12 (which binds to CXCR4 and CXCR7 receptors) fused to a luciferase (Gaussia luciferase: GL) (Abstract and page 2, last paragraph) as an alternate of fluorescent or GFP labeled chemokines and fluorescent or GFP labeled CXCL12 (page 2, lines 1-14). Luker teaches several advantages of utilizing bioluminescence-based detections. First, bioluminescence assays have substantially lower background signals than fluorescence, enhancing signal to noise ratios with improved sensitivity. Second, bioluminescent endpoints have a greater dynamic range of linear signal response than corresponding fluorescent probes and finally, bioluminescence assays are affected less than fluorescence by colors and dyes in compounds and cell culture media (page 2, 2nd paragaraph). Luker teaches that this technique can be generalized to develop bioluminescent probes for other chemokines and other peptide signaling molecules (page 2, last paragraph).
Therefore, given the fact that luciferase as reporter fused to binding partner (e.g. antibody or antigen) for detection of corresponding antigen/antibody expressed on cell surface is taught by Veniskin and Luker and since fusion of Gluc (Gaussia luciferase) as a reporter is advantageous for its enhancement of signal to noise ratios with improved sensitivity (Luker) and enhanced brightness and stability over other luciferases (Veniskin), it would be obvious to one of ordinary skilled in the art before the effective fining date of claimed invention, to easily envisage providing Oliveira with the Gluc luciferase for providing a fusion protein having Gluc with the CD19slg fusion construct of Oliveira with the expectation of providing alternative probe with different reporter system for optimization and for expanding the arsenal of probe for detection of CARs with a reasonable expectation of success. One of ordinary skilled in the art, from the above description in mind, can easily understand that in the construct of Oliveira, the CD19 antigen is the binding partner for anti-CD19 CAR on the cells and the fluorophore is the reporter system and the reporter system in view of Oliveira can be replaced with a luciferase reporter providing alternative detection probe for optimization with a reasonable expectation of success because Luker teaches that this technique can be generalized to develop bioluminescent probes for other chemokines and other peptide signaling molecules.
In regard to claims 3-6 for reporters fused with extracellular domain through covalent bond, non-covalent bond, intermediate molecule of fusion of one or more reporters, as described above, both Oliveira and Venisnik teaches providing fusion proteins and various linkages, spacers and fusion of one or more reporter would be considered obvious for optimization absent showing of unexpected advantages. Moreover, the linker as claimed in claim 3 is optional and the dependent claims 4-5 do not limit the fused construct having the linker but only describes what is the optional linker.
Regarding claim 7, Venisnik teaches the fusion protein with polyhistidine tag (page 268).
Regarding claims 14 and 15, Venisnik discloses substate coelentrrazine (page 268) and various other known substrate for luciferases would be considered obvious to one of ordinary skilled in the art.
In regard to claims 8 and 18, as described above, Oliveira teaches expression of CARs in T-lymphocytes from a subject and since the basic concept of detection of expressed CAR has been taught by the combination of the references, detection of expression in various immune cells and other types of cells collected from various samples and subjects, would be obvious to one of ordinary skilled in the art.
In regard to claim 16, the fusion protein having the fused luciferase reporter as found obvious from the combination of the references, being very similar to the claimed fusion protein, would be highly expected to detect at least 1000 CAR expressing cells in the background of 1 million non-CAR expressing cells absent showing otherwise by Applicant. Moreover, since the basic concept of detecting CAR expressing cells with the fusion protein comprising luciferase reporter fused to an extracellular domain of antigen targeted by the CAT has been found to be obvious in view of the combination of the references, various CAR containing molecules expressed on cell surface would be highly expected to be detected by the process as disclosed by the combination of the reference.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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