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
Applicant’s election of Group 3 (claims 32 and 36-39) in the reply filed on 1/6/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 32-34 and 36-39 are pending.
Claims 33-34 are withdrawn for being drawn to non-elected inventions (i.e., Groups 4-5). Because applicants have cancelled claims 1-3,5,10-12,15,18-22,24, 27-31, previously drawn to Groups 1-2, Groups 3-5 are being renamed as Groups 1-3, respectively.
Claims 32 and 36-39 are under examination.
Information Disclosure Statement
The Information Disclosure Statement filed on 8/17/2022 has been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 32, 36 and 38-39 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.
The written description in this case only sets forth a method of identifying an antigen-specific CD4+ T-cell comprising: contacting a T cell population with one or more stable multimers of a soluble human glycosylated MHC class II single chain trimer (SCT) protein, wherein the soluble human glycosylated MHC class II SCT comprises an HLA alpha chain extracellular domain, a linker1 an invariant chain, an antigen peptide or a placeholder peptide, liniker2 and HLA beta chain extracellular domain, in N-terminal to C-terminal, and therefore the written description is not commensurate in scope with the claims which read on a soluble human glycosylated MHC class II SCT comprises an HLA alpha chain, a linker1 an invariant chain, any peptide, liniker2 and HLA beta chain extracellular domain, in N-terminal to C-terminal.
The claims broadly encompass any peptide including one which is not immunogenic or two amino acids in length that is linked to HLA alpha chain extra cellular domain via a linker and a HLA beta chain extracellular domain via linker. However, the claims do not require that the genus of peptide is immunogenic peptide.
The specification on pg. 14, describes that a HLA alpha chain includes a human alpha chain or mouse alpha chain, wherein the human α chain is selected from an HLA-DR, HLA-DAP1, HLA-DPA2, HLA-DQA1 and HLA DQA2 α chain. The specification discloses HLA β chain can be a human β chain or a mouse HAL β chain, wherein the human HLA β chain is selected form an HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPB1, HLA-DPB2 and HLA-DQB1 β chain. The specification at pg. 15, discloses that a peptide is an antigenic peptide and the antigenic peptide fits in the binding pocket of an MHC class II protein complex that is recognized by CD4+ T cells. The specification does not disclose a how to determine whether a peptide is antigenic. The claims are drawn to a genus of peptide antigen that is not disclosed by the specification.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. Some of the factual considerations that are weighed when determining a written description include the level of skill and knowledge in the art, the disclosure of complete or partial structures, the disclosure of physical and or chemical properties, adequate disclosure of the functional characteristics, the correlation between structure and function, and disclosure of methods of making.
Zhu et al. (IDS, Eur. J. Immunol. 27, 1933-1941, 1997) teaches to prepare SCT having a secretion signal, an immunogenic peptide, a first linker (L1), an HLA β chain, a second linker (L2), and an HLA alpha chain. The art does not teach how to determine whether a peptide is an antigenic peptide or not. The specification and claims do not provide any guidance that could distinguish any peptide from an antigenic peptide. No common structural attributes identify the members of the genus. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an 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.
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the genus “a peptide that makes it antigen peptide” and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class.
Therefore, only method of identifying an antigen-specific CD4+ T-cell comprising: contacting a T cell population with one or more stable multimers of a soluble human glycosylated MHC class II single chain trimer (SCT) protein, wherein the soluble human glycosylated MHC class II SCT comprises an HLA alpha chain extracellular domain, a linker1 an invariant chain, an antigen peptide or a placeholder peptide, liniker2 and HLA beta chain extracellular domain, in N-terminal to C-terminal, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 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.
Claim(s) 32 and 36-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Thayer et al. (IDS, Mol. Immunol. 39, 861-870, 2003) in view of Zhu et al. (IDS, Eur. J. Immunol. 27: 1933-1941, 1997).
The instantly claimed invention is broadly drawn to a method of identifying an antigen-specific CD4+ T-cell comprising: contacting a T cell population with one or more stable multimers of a soluble human glycosylated MHC class II single chain trimer (SCT) protein, wherein the soluble human glycosylated MHC class II SCT comprises an HLA alpha chain extracellular domain, a linker1 an invariant chain, an antigen peptide or a placeholder peptide, liniker2 and HLA beta chain extracellular domain, in N-terminal to C-terminal (claims 32 and 36), wherein the peptide is an antigen peptide, a self-peptide or a place holder peptide (claim 37), and wherein the soluble human glycosylated MHC Class II SCT protein is a tetramer (claim 38).
Thayer et al. teach that the multimers of soluble histocompatibility complex class I and II molecules have proven to be useful reagents in quantifying and following specific T cell population (abstract). They identified a fragment invariant chain residue 58-85 that binds to a regional proximal to the class II peptide binding groove and stabilizes occupancy of the class II invariant chain associated peptide (abstract). They used linkers to make a membrane bound and a soluble single chain conjugate with the extracellular domain of the I-A alpha chain that is covalently linked with Aβ with a linker (see Fig. 1, page 864, right col.). They teach that the antigen specific T cells are stimulated by single chain I-Ab (page 866, left col.; 3.3 Antigen specific T cells). Thayer et al. do not teach to make a covalently linked heterotrimer of α-chain, β chain, and antigenic peptide.
Zhu et al. teach a recombinant single chain human class II MHC molecule (*HLA-DR1) covalently linked to heterotrimer of α-chain, β chain, and antigenic peptide (see the title, abstract, page 1934, left col. and Figure 2). They teach using HA specific peptide to stimulate HA-specific T cell (pg. 1938, 3.6 Recombinant DR1 molecule with HA peptide). Therefore, one skill in the art would be able to identify an antigen stimulated CD4+ T cell using Zhu et al.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a single chain trimer comprising α-chain, β chain, and antigenic peptide as taught by Zhu et al. to identify antigen peptide specific CD4+ T cell, wherein the antigen peptide is linked to extracellular domain of α-chain via a linker and to β chain extracellular domain via another linker as taught by Thayer et al. Additionally, one would have been motivated to do so prepare a single chain trimer (SCT) that comprises an α-chain extracellular domain linked via a linker to an antigenic peptide which is linked by another linker to β chain extracellular. Further, one would have a reasonable expectation of success in using a SCT comprising an extracellular domain of α-chain linked to an antigenic peptide linked to β chain extracellular domain for screening an antigenic peptide specific T cell as taught by Zhu et al. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
Claim(s) 39 is rejected under 35 U.S.C. 103 as being unpatentable over Thayer et al. (IDS, Mol. Immunol. 39, 861-870, 2003) in view of Zhu et al. (IDS, Eur. J. Immunol. 27: 1933-1941, 1997) as applied to claims 32 and 36-38 above, and further in view of Santamaria P. (US Pat. No. 10,988,516).
The instantly claimed invention of claim 39 is broadly drawn to the method of claim 32, wherein the stable multimer of the soluble human glycosylated MHC class II SCT protein is attached to a polymer or a nanoparticle scaffold.
Neither Thayer et al. nor Zhu et al teach attaching the soluble human glycosylated MHC class II SCT protein is attached to a polymer or a nanoparticle scaffold.
Santamaria P. teaches to use nanoparticles to attach antigen MHC to make antigen-MHC nanoparticle complex (col.1, lines 37+, col. 2, liens 40+). They teach that nanoparticles are biocompatible polymer made from PLGA (col. 7, lines 2+). They teach a method of coupling a protein or peptide with a nanoparticle (col. 17, lines 53+).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a nanoparticle as taught by Santamaria P. to attach it with single chain trimer comprising α-chain extracellular domain, β chain extracellular domain and antigenic peptide as taught by Thayer et al. in view of Zhu et al. to screen antigen peptide specific CD4+ T cell. Additionally, one would have been motivated to do so because attaching a nanoparticle facilitate the process of labelling or even sorting out a cell associated with nanoparticle complex as taught by Santamaria P. Further, one would have a reasonable expectation of success in using a nanoparticle for adsorption or labelling is routine in the art. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
“Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989); see also MPEP §716.02(c). Additionally, “[it] is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674