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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/EP2019/080929 filed 11/12/2018, which claims the benefit of the priority of European Patent Application No. EP18205615.0 and EP18205611.9 filed 11/12/2018.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 1-7, 9-23 are pending. Claims 9, 14-23 are withdrawn. Claims 1-3 are amended. Claims 1-7, and 10-13 are being examined on the merits in this office action.
Claim Rejections – Withdrawn
The rejection of claims 1-7, 10-13 under 35 U.S.C. 102(a)(1) as being anticipated by Remy (WO2016059236A1 - hereinafter “Remy”) is withdrawn in view of the claim amendments.
The rejection of claims 1-7, 10-13 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-29, 31 of copending Application No. 17/292,888 is withdrawn because the application is abandoned.
Claim Rejections - 35 USC § 103 - New
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.
Claims 1, 4-7, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Remy (WO2016059236A1 - hereinafter “Remy”) in view of French et al. (J. Mol. Evol. 1983, 19: 171-175) and Sousa et al. (Journal of Thrombosis and Haemostasis, 15: 774–784).
Remy teaches immunogenic peptides comprising an MHC class II T cell epitope, and immediately adjacent or separated from said epitope [CST]-X(2)-C-X(0,2)-H, wherein X is Gly or Pro (Abstract; page 2, line 1-34; page 3, line 1-3). Examiner notes the teachings of Remy read on the instant CXX[CST](B2)m(Z3)+, wherein the sequence is C, GG(for X2, wherein X is Gly or Pro), C, G (for B2) and H (for instant Z3 which is a basic amino acid). The sequence is thus CGGCGH. Further, Remy teaches the sequence CXXCXH (SEQ ID NO: 94), wherein X represents any amino acid. This sequence reads on the instant sequence CXX[CST](B2)m(Z3), wherein X is any amino acid, (B2) is any amino acid, m is an integer from 0-3, and (Z3) is a basic amino acid K or R. Thus the sequence of Remy CXXCXH (SEQ ID NO: 94), reads on the instant sequence because it has the first amino acid as C, the fourth amino acid is C and the last amino acid is H which is a basic amino acid. Remy teaches T cell epitope and the modified redox motif sequence may be immediately adjacent to each other in the peptide or optionally separated by a one or more amino acids (so called linker sequence), (Page 11, line 1-6), and that the linker comprises 1,2,3,4 amino acids (Page13, line 30-37).
Even though Remy teaches that (Z3) is the basic amino acid H, Remy does not teach that (Z3) is the basic amino acid K or R. Examiner notes that H, K and R are all basic amino acids as taught by French et al.
French teaches that H, K and R are all basic amino acids and that these amino acid can be conservatively substituted between each other.
Further, Sousa teaches redox motif having the sequence CXXC (Abstract) and that further that the motif can have the sequence CGHCK (page 775, right col., line 13; Fig. 1). Examiner notes that the sequence of Sousa reads on the instant sequence CXX[CST](B2)m(Z3)+, wherein m is 0, and (Z3)+ is K.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the peptide of Remy and conservatively substitute H with either K or R, since they are all basic amino acids that can be conservatively substituted without changing the property of the amino acid as taught by French. Further, It would have been obvious use K or R in that position since Souza teaches same motifs with a lysine (K) at the instant position. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using other basic amino acids in place of H such as K and R since it is known in the art as taught by French to conservatively substitute amino acids in the same group. The disclosures render obvious claim 1.
Regarding claims 2-3, Sousa teaches redox motif having the sequence CXXC (Abstract) and that further that the motif can have the sequence CGHCK (page 775, right col., line 13; Fig. 1). Examiner notes that the sequence of Sousa reads on the instant sequence CXX[CST](B2)m(Z3)+, wherein m is 0, and (Z3)+ is K. further, French teaches conservative substitution with K or R, thus it would have been obvious to modify the peptide of Remy and conservatively substitute H with either K or R, since they are all basic amino acids that can be conservatively substituted without changing the property of the amino acid as taught by French.
Regarding claim 4, Remy teaches immunogenic peptides comprising an MHC class II T cell epitope, and immediately adjacent or separated from said epitope [CST]-X(2)-C-X(0,2)-H, wherein X is Gly or Pro (Abstract; page 2, line 1-34; page 3, line 1-3).
Regarding claim 5, Remy teaches that the epitope comprises 8-25 amino acids (Page 15, line 10-14; page 16, line 35-36).
Regarding claim 6, Remy teaches that the length of the peptide vary from 13 or 14 amino acids (page 16, line 35-36).
Regarding claim 7, Remy teaches where the antigen is an auto- antigen (claims 16-17).
Regarding claim 10, Remy teaches immunogenic peptides comprising an MHC class II T cell epitope, and immediately adjacent or separated from said epitope [CST]-X(2)-C-X(0,2)-H, wherein X is Gly or Pro (Abstract; page 2, line 1-34; page 3, line 1-3).
Regarding claim 11, Remy teaches T cell epitope and the modified redox motif sequence may be immediately adjacent to each other in the peptide or optionally separated by a one or more amino acids (so called linker sequence), (Page 11, line 1-6), and that the linker comprises 1,2,3,4 amino acids (Page13, line 30-37).
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Remy (WO2016059236A1 - hereinafter “Remy”) in view of French et al. (J. Mol. Evol. 1983, 19: 171-175) and Sousa et al. (Journal of Thrombosis and Haemostasis, 15: 774–784) as applied to claim 1 above, and further in view of Remy-2 (US20160194367A1 - hereinafter “Remy-2”).
The teachings of Remy are disclosed above and incorporated herein by reference.
Remy does not teach wherein said oxidoreductase motif does not naturally occur within a region of 11 amino acids N-terminally or C-terminally of the T-cell epitope in said antigenic protein as recited in claim 12.
Remy-2 teaches an isolated immunogenic peptide of between 12 and 75 amino acids comprising: an MHC class II T cell epitope of an allergen or auto-antigen; and a C-X(2)-[CST] or [CST]-X(2)-C redox motif, and wherein X is an amino acid, wherein said redox motif is either immediately adjacent to said epitope, or is separated from said epitope by at most 7 amino acids, and wherein the sequence of said allergen or autoantigen does not comprise said redox motif within a sequence of 11 amino acids N or C terminal of said epitope (claim 37), that the amino acid X in the [CST]-X(2)-[CST] motif of particular embodiments of the reducing compounds of the invention can be any natural amino acid, including S, C, or T or can be a non-natural amino acid [0107]. Remy-2 teaches that the peptides of the invention have been shown to be useful a medicine, more in particular for the prevention or treatment of immune disorders, more specifically of allergic disorders or autoimmune diseases (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Remy and use the oxidoreductase motif that does not naturally occur within a region of 11 amino acids N-terminally or C-terminally of the T-cell epitope as taught by Remy-2 so as to further increase the immunogenic properties described herein [0136]. One of ordinary skill in the art would have had a reasonable expectation of success in doing so since Remy-2 teaches that the peptides of the invention have been shown to be useful a medicine, more in particular for the prevention or treatment of immune disorders, more specifically of allergic disorders or autoimmune diseases (Abstract).
Regarding claim 12, Remy-2 teaches wherein the sequence of said allergen or autoantigen does not comprise said redox motif within a sequence of 11 amino acids N or C terminal of said epitope (claim 37, 46; [0011, 0022, 0024]). It would have been obvious to one of ordinary skill in the art to modify the teachings of Remy and use the oxidoreductase motif that does not naturally occur within a region of 11 amino acids N-terminally or C-terminally of the T-cell epitope as taught by Remy-2 so as to further increase the immunogenic properties described herein [0136].
Regarding claim 13, Remy teaches that the T-cell epitope is an epitope of an antigenic protein which does not naturally comprise the motif [0022]. It would have been obvious to one of ordinary skill in the art to modify the teachings of Remy and use the oxidoreductase motif that does not naturally occur so as to further increase the immunogenic properties described herein [0136].
Response to Arguments
Applicant's arguments filed 10/16/2025 have been fully considered but they are not persuasive.
Applicant Arguments
Applicant argues that the instant immunogenic peptides comprising the oxidoreductase motif recited in instant claim 1 outperform the control immunogenic peptides comprising the classical CXXC or HCXXC domains in the activation of antigen-specific CD4 T cells. (Page 9-10 of Arguments).
Applicant argues that Souza would not have modified Remy's teachings by incorporating the VEFYAPWCGHCK peptide because Souza teaches that the VEFYAPWCOHCK peptide inhibits PDI reductase activity.
Examiner’s Response
The arguments presented above have been fully considered but are unpersuasive. Examiner notes that the cited references disclose or render obvious the instant moiety because they disclose the instant moiety. Further, the cited reference teach that the cited reference a high reductase activity (See Table in Example 10). Further, Examiner notes that Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (See MPEP 716.02(d). Examiner notes that the argument that the motifs KCPYC, KHCPYC, CHGCHK, CHGCK, CPYCHK and CPYCK, outperformed CPYC is unpersuasive because the cited references teach or render obvious the motif CGGCGH and CGHCK and Remy teaches that the peptides had high reductase activity (See Table in Example 10). Further, the instant claims recite that X, B1 and B2 can be any amino acid. The claims are not limited to the motifs that Applicant argues displayed superior results. Further, from Fig. 2, it is the motif KCPYC that displayed better results. The arguments are unpersuasive.
With regards to the argument that the Souza cannot be combined with the Remy references because it inhibits PDI reductase activity, Examiner disagrees. The CXXC motifs are known in the art and are known as oxidoreductase motifs. One of ordinary skill in the art would be motivated to modify Remy and use the oxidoreductase motifs of Souza. This argument is unpersuasive.
Double Patenting - Maintained
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 1-7, 10-13 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-14,of copending Application No. 17/923,117.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite an immunogenic peptide, said immunogenic peptide comprising: a) an oxidoreductase motif, b) an MHC class II T-cell epitope of an antigenic protein, and c) a linker between a) and b) of between 0 and 7 amino acids, wherein [[:]] said oxidoreductase motif has the following sequence: Z(B)n[CST]XmC- or Z(B)nCXm[CST]-;wherein Z is any amino acid or non-natural amino acid, excluding basic amino acids wherein (B) is any amino acid; wherein n is an integer of 0 to 2; wherein C is Cysteine, S is Serine and T is Threonine; wherein X is any amino acid; wherein m is 2, 0, 1, or 3; and wherein the hyphen (-) in said oxidoreductase motif indicates the point of attachment of the oxidoreductase motif to the N-terminal end of the linker (c) or the epitope (b), or to the C- terminal end of the linker (c) or the epitope (b) (claim 1).
The claims of the instant application recite an immunogenic peptide, said immunogenic peptide comprising:
a) an oxidoreductase motif,
b) a T-cell epitope of an antigenic protein, and
c) a linker between a) and b) of between 0 and 7 amino acids
wherein:
(i) said oxidoreductase motif is selected from the group comprising:
(Z2)+(B1)n[CST]XXC or (Z2)+(B1)nCXX[CST];
wherein (Z2)+ is a basic amino acid which is not H;
wherein X is any amino acid; wherein (B1) is any amino acid and wherein n is an integer from 0 to 3 (claim 1).
The claims of the copending application anticipate the instant claims.
Regarding claim 2-3, the claims of the copending application recite wherein one or more X is a basic amino acid selected from the group consisting of R, K and H (claim 6).
Regarding claim 5, the claims of the copending application recite wherein said epitope has a length of between 9 and 30 amino acids (claim 8).
Regarding claim 6, the claims of the copending application recite peptide having a length of between 12 and 50 amino acids (claim 9).
Regarding claim 7, the claims of the copending application recite wherein said antigenic protein is an auto-antigen, a soluble allofactor, an alloantigen shed by the graft, an antigen of an intracellular pathogen, an antigen of a viral vector used for gene therapy or gene vaccination, a tumor-associated antigen or an allergen (claim 10).
Regarding claim 10, the claims of the copending application recite wherein at least one X in the oxidoreductase motif is P (proline) or Y (Tyrosine) (claim 14).
Regarding claim 11, the claims of the copending application recite wherein the linker is of between 0 and 4 amino acids (claim 11).
Regarding claim 12, the claims of the copending application recite wherein said oxidoreductase motif does not naturally occur within a region of 11 amino acids N-terminally or C-terminally of the MHC class II T-cell epitope in said antigenic protein.
Regarding claims 4 and 13, the claims of the copending application recite wherein the MHC class II T-cell epitope does not naturally comprise said oxidoreductase motif.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 10/16/2025 have been fully considered but they are not persuasive.
Applicant argues that since the double patenting rejections are the only rejections remaining, that rejection should be withdrawn since they are the application is earlier filed.
Examiner notes that the instant application currently contains a 102 and 103 rejections. The rejections are thus maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654