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 .
Claims 1-20 are pending and examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 19 requires the peptide of claim 1, wherein said peptide is produced by solid phase synthesis, expression in a yeast cell or expression in a bacterial cell. Solid phase synthesis will produce a peptide identical to the instant SEQ ID NO:81. Both expression in yeast or bacterial cells will produce a peptide identical to SEQ ID NO:81. It is noted that yeast can carry out post-translational modification, such as glycosylation, but the instant peptide does not comprise the motif required for glycosylation, Asn-X-Ser/Thr. Thus, the peptide produced by any of the processes of claim 19 will be identical to the peptide of claim 1 and not further limiting. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 2 states that the peptide of claim 1 has the ability to bind to an MHCI molecule and when bound is capable of being recognized by CD8T cells. The specification teaches that SEQ ID NO:81 binds to HLA-A2 (page 20, line 3 under “Detailed Description”). The specification teaches that
In case of a MHC class I epitope being used as an antigen, the T cells are CD8-positive T cells (page 144, last two lines).
Because SEQ ID NO: 81 is presented by HLA-A2, it is a MHC class I epitope, and the recognizing T cells are CD8 positive T cells according to the specification. The ability of SEQ ID NO: 81 to bind to MHC class I and be recognized by a CD8 T cell is an inherent property of SEQ ID NO:81. Thus, claim 2 fails to further limit claim 1 being drawn to the identical peptide..
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.
Claim 8 is 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.
(A)Claim 8 is vague and indefinite in the recitation of an incorrect Markush group format. Claim 8 recites CpG oligonucleotides and derivatives, poly-(I:C) and derivatives rather than CpG oligonucleotides, derivatives of CpG oligonucleotides, poly-(I:C), poly-(I:C) derivatives. Thus claim 8 is not in the format of “selected from the group consisting of A, B C and D” and it is unclear what constitutes the elements of the group.
(B)The recitation of the species of oligonucleotides, derivatives, particulate formulations and virosomes in the plural is vague and indefinite in that it is unclear if multiple oligonucleotides, derivatives, particulate formulations and virosomes are needed to satisfy the claim limitations.
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.
Claim 2 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claim 2 requires that the peptide of claim 1 has the ability to bind to an MHC-I molecule, and wherein said peptide, when bound to the MHC is capable of being recognized by CD8 T cells.
The specification teaches that the peptide of SEQ ID NO:81 is over-presented on tumors relative to normal tissues (pages 157 and 159, Table 8). When given the broadest reasonable interpretation “MHC I molecule” includes HLA-A*01, -A*03, -A*11, A*23 to A*34 and HLA-B alleles (Hurley et al, Tissue Antigens, 1997, Vol. 50, pp. 401-418, see Tables 1 and 2, pp. 404-410). The specification teaches that SEQ ID NO:81 binds to HLA-A*02 (page 20, line 3 under “Detailed Description). The specification fails to provide any objective evidence that a peptide consisting of SEQ ID NO: 81 is expressed in the context of other types of HLA molecules outside of HLA-A*02 on tumor cells or APC cells. One of skill in the art would understand that SEQ ID NO:81 may bind to other MHC I antigens with non-optimal affinity. The art teaches that T cell activation is determined by the TCR-pMHC binding parameters but there is no predictive model relating the TCR-pMHC binding interaction to a T cell activation that is consistent with the published data and that there is a need for additional quantitative experimental data to establish a more definitive model (Lever et al, Nature Reviews Immunology, 2014, Vol. 14, pp. 619-629, see page 619, first column, lines 10-17 and second column, lines 26-28). The specification fails to provide any teachings of guidance regarding the potential display of SEQ ID NO: 81 by other HLA-A or HLA-B antigens, and the resulting ability of the display of SEQ ID NO: 81 in a non-HLA-A*02 cleft to recognize and activate CD8+T cell. One of skill in the art would be subject to undue experimentation in order use the peptide in the context of other MHC I antigens outside that of HLA-A*02.
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.
Claims 1 and 3-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,618,948 in view of Bender et al (U.S. 10,137,182), Roberts et al (Advanced Drug Delivery Reviews, 2002, vol. 54, pp. 459-476) and Beck et al (Biologicals, 2001, vol. 29, pp. 293-298).
Claims 1-11 of ‘948 teach the peptide of SEQ ID NO: 81. Claim 1 of ‘948 taches that the administration of the peptide produces activated antigen-specific T cells, which meets the limitations of instant claim 2
The clams of the patent do not teach the peptide of SEQ ID NO:81 in the form of a pharmaceutically acceptable salt,, a composition comprising the peptide and an adjuvant in a pharmaceutically acceptable carrier
Bender et al teach a composition comprising a pharmaceutically acceptable carrier, an adjuvant and at least one MHC class I peptide epitope, wherein the MHC class I peptide epitope is pegylated (claims 1 and 8 of ‘532), wherein the composition further comprises dextrose (claim 4 of ‘182) which meets the same limitation of instant claim 18. Bender et al teach that the peptides and adjuvants can be dissolved or suspended in a pharmaceutically acceptable carrier (column 26, lines 34-37), and that such composition can further comprise buffers, excipient and immune stimulating substances (column 26, lines 37-40) which meets the same limitation in instant claim 20 because one of skill in the art would understand that a buffered solution requires water. Bender et al teach that peptides can be administered with adjuvants to render the composition more immunogenic (column 26, lines 3-4) Bender et al teach the specific adjuvants of GM-CSF, CpG7909, Imiquimod resiquimod, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, Interferon-α or -β, poly(lactid co-glycolid) [PLG]-based and dextran microparticles, virosomes cyclophosphamide, sunitinib, bevacizumab, sildenafil, CP-547,632, which meets the same limitations in claim 8.
Beck et al teach that the large majority of research grade peptides are produced as trifluoroacetate salts which take advantage of a classical reverse-phase HPLC purification step using Trifluoroacetic acid as the peptide solubilizing step (page 297, lines 7-10). Beck et alt each that the therapeutic peptides which are “on the market” are registered as acetate salts (page 297, first column, lines 10-13). Beck et al teach that the HCL salt is used in many marketed drugs bearing amino groups and that after mixing with adjuvant protein and peptide provides a composition which exhibits similar CTL activities and MHC binding stability (page 297, second column, line 14 to page 298, first column, line 2).
Roberts et al teach that reasons for Pegylation of peptides includes shielding from receptor-mediated uptake by the reticuloendothelial system and preventing recognition and degradation by proteolytic enzymes, and increasing the apparent size of the peptide to reduce renal filtration (abstract), which meets the limitation of sustained release preparation in claim 18.
It would have been prima facie obvious at the time prior to the effective filing date to PEGylate the peptide consisting of SEQ ID NO:81 and to provide a composition comprising the pegylated peptide in phosphate buffered saline or a solution of sodium acetate. One of skill in the art would have been motivated to make the pegylated peptide of SEQ ID NO:81 by the teachings of Bender et al regarding the pegylation of a MHC class I epitope, and the teachings of Roberts et al that Pegylation of peptides shields from receptor-mediated uptake by the reticuloendothelial system, preventing recognition and degradation by proteolytic enzymes, and increasing the apparent size of the peptide to reduce renal filtration. One of skill in the art would understand that all said effects will serve to increase the half-life of the peptide in serum after administration. It would have been prima facie obvious that the composition of claims 12-20 of the patent comprising a pharmaceutically acceptable salt and an adjuvant including water because Bender teaches that the peptide composition comprises a pharmaceutically acceptable carrier and that the peptides can be administered parenterally.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643