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 .
1. Formal Matters
Claims 1-7, 9-11, 14, 17-21, 23-25, 27 and 29-34 are pending and are the subject of this Office Action.
2. Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A. Claims 1, 2, 7, 9-11 19, 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 2020/0172597 - cited as RUBIUS on the IDS filed 11/6/23).
The claims are drawn to nucleic acids and encoded proteins of a MHC Claims I SCT, wherein the SCT comprises a peptide, b2m and HLA
Chen teaches a nucleic acid fragment pair comprising and first and second nucleic acid fragment which can assemble to form the SCT of instant claim 1. Figure 1 of Chen is “a schematic showing an exemplary construct of an antigen-presenting polypeptide comprising an HLA-E polypeptide. In this construct, an exogenous antigenic polypeptide is linked to the β2M polypeptide, which is linked to one or more alpha domains of an HLA-E alpha chain (e.g., alpha1, alpha2, and alpha3 domains), which is linked to a membrane anchor, such as GPA or SMIM1.”
Chen does not teach where the first and second nucleic acids comprise a portion of the b2m protein. However, separating a nucleic acid construct into smaller self-assembling fragments was well-known in the prior art at the time of the instant invention, as this would have increased transfection efficiency into a host cell as well as to have allowed an easier means of combining various subunits based on the desired study.
Regarding claim 2, Gibson assembly is taught in paragraph [0401].
Claim 7 is met by paragraph [0060].
Claim 9 is met by paragraph [0082].
Claim 10 is met by paragraphs [0177] and [0275].
Claim 11 is met throughout the specification (e.g. [0275]).
Claim 14 is met by paragraph [0177].
Claims 19 and 21 are met by the Abstract, Figures 1 and 2, paragraph [0060] and paragraph [0265].
B. Claims 20, 27 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. in view of Lyu et al. (cited on the IDS filed 11/6/23)
The teachings of Chen are seen in paragraph A of this section. Chen does not teach soluble SCT. However, Lyu does teach the advantage of producing this soluble protein, stating their approach is a “technically simple method that does not require protein refolding in vitro has been developed for the high-throughput generation of soluble and functional p/MHC-single chain trimer (SCT) monomers and tetramers in a mammalian cell system” (Abstract). The teaching of “tetramers” meets claim 27. Regarding claim 29, paragraphs [0429] and [0494] teach modification of a protein by attaching to a polymer.
C. Claim 17, 18, 30 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. in view of either (1) Gee et al. (cited as LELAND STANFORD JR UNIVERSITY on the IDS filed 11/6/23) or (2) Bethune et al. (cited as PACT PHARMA on the IDS filed 11/6/23).
The teachings of Chen are seen in paragraph A of this section. Chen does not teach libraries. However, Gee does teach the use of peptide-MHC libraries (paragraph [0011]) and peptide-HLA libraries (paragraph [0015] and Figures 1A-F). See also paragraphs [0039], [0057], [0058]. It would have been obvious at the time of the instant invention to have produced libraries for the trimers of Chen using the techniques of Gee I order to improve screening efficiency regarding, for example, structure-function.
Furthermore, Bethune teach a similar construct to Chen (Bethune – paragraphs [0007], [0011]; Figures, 1, 6, 11; claims 1) as well as libraries – e.g. claims 66 and 111).
D. Claims 3, 5 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. in view of Bethune et al.
The teachings of Chen are seen in paragraph A of this section. Chen does not teach purification tags. However, Bethune does teach constructs comprising purification tags, including purification clusters with biotinylated sequences (e.g. paragraph [0066]; Figures 1, 2, 6).
E. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Bethune et al. in view of Stengel et al. (US 2021/0214416 – based off of WO 2020/072390 cited on the IDS filed 11/6/23).
The teachings of Chen are seen in paragraph A of this section. Chen does not teach an HLA secretion sequence. However, Figure 2B of Stengel teaches essentially the same construct as Bethune and paragraph [0126] of Stengel teaches a signal sequence. Though a secretion sequence, which is a type of signal sequence, is not taught, it would have been obvious at the time of the instant invention to have added a signal sequence, including a secretion sequence, in order to allow for targeting and/or secretion of the protein from the cell.
F. Claims 6 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. in view of Siedel et al. (US 2020/0317747 – cites as CUE BIOPHARMA on the IDS filed 11/6/23).
Chen teaches Y84A ([0196]), but does not teach SEQ ID NO:3. However, Siedel does teach this HLA-A02 sequence (paragraph [0095] regarding SEQ ID NO:302, which is identical to instant SEQ ID NO:3). Siedel teaches the Y84A mutation in paragraph [0196]. It would have been obvious to have used the SEQ ID NO:302 with the Y84A mutation to product an SCT in order to, for example, study the effects of overall protein structure and function based on this mutation
G. Claims 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. in view of Thayer et al.
The teachings of Chen are seen in paragraph A of this section. Chen does not teach a method of identifying antigen-specific CD8+ T cells. However, Thayer (Abstract) teaches “Multimers of soluble major histocompatibility complex class I and II molecules have proven to be useful reagents in quantifying and following specific T cell populations”.
Regarding claims 33 and 34, though neither reference teaches sequencing, it would have been obvious to have sequenced the identified TCR in order to produce a population of T cells expressing the specific TCR for therapeutic purposes.
3. Prior Art of Interest Not Relied Upon
A. Zhang teaches that “single-chain trimers (SCT) composed of peptide epitope b2 -microglobulin (b2 m) and major histocompatibility complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses”. Zhang also used vectors comprising SCT nucleic acids for the “transfection of NIH-3T3 cells with pcDNA3.0-SCT-C 18)27 and SCT-C 107)115 leads to stable presentation of HBcAg epitopes at the cell surface”. Finally, Zhang teaches that “our data indicate that a DNA vaccine encoding a human HLA-A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA-A2-positive HBV carriers”.
The only essentially difference between Zhang and the instant invention is that the instant invention utilizes two nucleic acid fragments. Regarding claim 19, Zhang does not appear to teach any more than Chen, cited above, under 35 USC 103.
B. Hansen (Abstract) teaches –
This unit describes a method for constructing a class I MHC molecule with a bound peptide as a single polypeptide chain, termed SCT, for single chain trimer. The component organization of the SCT appears to be widely applicable to different mouse or human MHC class I isotypes bound by different antigenic peptides. The enhanced peptide occupancy afforded by the SCT format makes these molecules effective reagents as DNA vaccines, multimeric staining reagents to enumerate CD8 T cells, and probes of lymphocyte biology.
See also Figure 17.5.1 and Table 17.5.1. However, the reference does not teach any more than Chen, cited above, under 35 USC 103.
4. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
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