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 .
The amendment filed 1/23/2026 has been entered. Claims 1,5, 11, 13, 15-17, 19-20, 25-26, 28-29, 36-37, 41, 64, 67 and 68 are pending. Claims 64 and 67-68 are withdrawn.
Claims 1,5, 11, 13, 15-17, 19-20, 25-26, 28-29, 36-37 and 41 are under examination.
Claim Rejection, Objections Withdrawn
The objection to claim 15 is withdrawn in view of the amendment to the claim.
The rejection of claims 25, 29 and 36 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment to the claims.
Claim Rejections - 35 USC § 102 Maintained
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claim(s) 1, 5, 11, 13, 15-17, 19, 26, 28-29, 37 and 41 under 35 U.S.C. 102(a)(2) as being anticipated by Schwendt et al. WO2020128031 6/25/2020 filed 12/21/2018 is maintained.
Claim 1 and claim 19: Schwendt et al disclose an immunogenic fusion protein (such as SEQ ID NO: 8746) comprising an immunogenic peptide or an immunogenic variant thereof, the immunogenic peptide comprising the following motifs:
KQPAa;
NPDPb
NANPc; ANPNc; NPNAc; or PNANc;
NVDPd, and
NANPe; ANPNe; NPNAe; or PNANe.
wherein a, b, c, d, e is at least 1 and wherein a+b+c+d+e is at least 2; and
a nanocage monomer peptide at least 99% identical to SEQ ID NO: 18.
Other nanocage monomer peptides include hepatitis b surface antigen (HBsAg)
See alignment of SEQ ID NO: 18 with SEQ ID NO: 8746. Appendix A
See alignment of SEQ ID NO: 22 with SEQ ID NO: 8746. Appendix B.
See Schwendt et al p. 31 lines 10-40.
Claim 5: In the fusion protein of Schwendt et al a is 1; b is 1; c is 1; d is 3 and e is 5 or 18.5. See alignment with SEQ ID NO: 30. Appendix C.
Claim 11: in the fusion protein of Schwendt et al c and e are greater than 1 such that the respective motif is at least partially repeated, the repeated motifs are each independently contiguous or non-contiguous. See Appendix C.
Claim 13: SEQ ID NO: 8746 of Schwendt et al comprises the motif in the order KQPAa-NPDPb-NANPc-NVDPd-NANPe (SEQ ID NO: 17): KQPADGNPDPNANPNVDPNANP.
Claim 15 and claim 17: the nanocage monomer is ferritin from H. pylori.
Claim 16 and claim 26: Schwendt et al disclose that ferritin is a multimerization or antigen clustering domain that can self-assemble into protein nanoparticles – thus the ferritin is provided as two or more self-assembling subunits to form nanoparticles. See p. 25 lines 20-45, p. 26 lines 28-40,
Claim 28-29: Schwendt et al disclose the peptide comprises autologous T cell help provided by a PfCSP T cell peptide epitope or a PADRE epitope. See p. 15 lines 14-32, p. 17 lines 30-45, p. 18, p. 19, p. 24 lines 23-30, p. 43-44 table 5 disclosing PfCSP T cell epitopes, PADRE, ferritin).
Claim 37: SEQ ID NO: 8746 of Schwendt et al comprises a functional variant of SEQ ID NO: 30 or a fragment thereof. See alignment in appendix C.
Claim 41: Schwendt et al disclose the fusion protein. Claim 41 does not comprise any other component(s) in addition to the fusion protein. Thus, the disclosure of the fusion protein anticipates claim 41.
Response to Applicant’s Argument
Applicants states that the immunogenic peptide excludes the C-terminal Domain of PfCSP. This is not found persuasive. “C terminal domain” does not convey an particular C terminal domain sequence of PfCSP. The protein of Schwendt et al does not comprise a C terminal domain sequence of PfCSP and thus meets the limitation of excludes the “C terminal Domain”. Applicant can obviate this issue by reciting which residues of PfCSP are excluded. Limitations from the specification are not read into the claims and the instant specification does not specifically define “C terminal domain of PfCSP.
Even if the residues covering “C terminal Domain” are recited, this is with regards to the immunogenic peptide. The fusion protein of Schwendt et al will still be regarded as an immunogenic variant thereof.
The rejection of claim(s) 1, 5, 11, 13, 15-17, 19, 26, 28-29, 37 and 41 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Daubenberger et al. WO2018193063 10/25/2018 filed 4-19-2018 cited in IDS is maintained.
Claim 1 and claim 15: Daubenberger et al disclose an immunogenic fusion protein comprising:
an immunogenic peptide or an immunogenic variant thereof, the immunogenic peptide comprising NPDPb and NANPc (p. 18 SEQ NO: 5, 6);
an immunogenic peptide or an immunogenic variant thereof, the immunogenic peptide comprising NPDPb and NANPc (p. 19-p. 22, SEQ ID NO: 7-23) or
wherein a=1, b=1, c is greater than 0, d=0 and e is greater than 0 and wherein a+b+c+d+e is at least 2; and
a nanocage monomer peptide such as ferritin, sulfur oxygenase reductase (SOR), lumazine synthase, and pyruvate dehydrogenase. See p. 36 lines 9-31.
See p. 12, p. 22-23 and p. 26-27.
Claim 2: the combination of b and c is at least about 1.
Claim 5: Daubenberger et al disclose another immunogenic peptide for the fusion protein comprising KQPAa a=1; NPDPb b=1; NANPc c=1; NVDPd d=3 and NANPe e is 5 or 18.5. See figure 4B.
Claim 11: in the fusion protein of Daubenberger et al d, and e is greater than 1 such that the respective motif is at least partially repeated, the repeated motifs are each independently contiguous or non-contiguous. See figure 4B, p. 12, p. 22-23 and p. 26-27.
Claim 13: in the fusion protein of Daubenberger et al, the motifs are in the order KQPAa-NPDPb-NANPc-NVDPd-NANPe (SEQ ID NO: 17). See figure 4B, p. 12, p. 22-23 and p. 26-27.
Claim 16-17 and claim 26: Daubenberger et al et al disclose that the ferritin is H. pylori ferritin which is made up of monomeric subunits which forms nanoparticles (nanocage). See p. 37-p. 39.
Claim 19: The ferritin of Daubenberger et al (SEQ ID NO: 331) comprises an amino acid sequence 99.3% identical to SEQ ID NO: 18:
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Claim 28-29: Daubenberger et al disclose the PfCSP protein which comprises the PfCSP T cell peptide epitope. See figure 4B, p. 12, p. 22-23 and p. 26-27.
Claim 37: The immunogenic peptide of Daubenberger et al is a functional variant or fragment thereof of SEQ ID NO: 26-30 e.g. See SEQ ID NO: 5-23 of Daubenberger et al.
Claim 41: Daubenberger et al disclose a vaccine comprising the fusion protein. See p. 113-128 under pharmaceutical composition.
Response to Applicants Argument
Applicants argument that the reference fails to exclude the C terminal domain of PfCSP and fails to teach specific motifs has been carefully considered but is not found persuasive. Even if “C terminal Domain of PfCSP” are excluded, this is with regards to the immunogenic peptide. The fusion protein of Daubenberger et al et al will still be regarded as an immunogenic variant thereof. Regarding claim 37, the immunogenic peptide of Daubenberger et al is a functional variant or fragment thereof of SEQ ID NO: 26-30 e.g. See SEQ ID NO: 5-23 of Daubenberger et al.
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.
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.
The rejection of claim(s) 1 and 20 under 35 U.S.C. 103 as being unpatentable over Schwendt et al. WO2020128031 6/25/2020 filed 12/21/2018 in view of Nabel et al. WO 2019/195316 10/10/19 filed 4/2/19 is maintained.
Claim 1: Schwendt et al disclose an immunogenic fusion protein (such as SEQ ID NO: 8746) comprising an immunogenic peptide or an immunogenic variant thereof, the immunogenic peptide comprising the following motifs:
KQPAa;
NPDPb
NANPc; ANPNc; NPNAc; or PNANc; and
NANPe; ANPNe; NPNAe; or PNANe.
wherein a=1, b=1, c is greater than 0, d=0 and e is greater than 0 and wherein a+b+c+d+e is at least 2; and
a nanocage monomer peptide at least 99% identical to SEQ ID NO: 18.
Other nanocage monomer peptides include hepatitis b surface antigen (HBsAg)
See alignment of SEQ ID NO: 18 with SEQ ID NO: 8746. Appendix A
See alignment of SEQ ID NO: 22 with SEQ ID NO: 8746. Appendix B.
See Schwendt et al p. 31 lines 10-40.
Schwendt et al does not disclose the nanocage monomer peptide ferritin is modified to reduce an anti-nanocage monomer peptide immune response.
Nabel et al disclose ferritin nanoparticles for use in immunization (paragraph 209), wherein the ferritin comprises a mutation to inhibit formation of a N-glycan (paragraph 286). Nabel et al disclose a mammal exposed to a glycosylated protein produced in bacteria or yeast may generate an immune response to the glycosylated protein, because the pattern of glycosylation of a given protein in bacterial or yeast could be different from the pattern of glycosylation of the same protein in a mammal. Thus, some glycosylated therapeutic proteins may not be appropriate for production in bacteria or yeast. See paragraph 288. Nabel at [00289] disclose that decreased glycosylation ferritin by amino acid mutation facilitates protein production in bacteria or yeast. In some embodiments, decreased glycosylation of ferritin reduces the potential for adverse effects in mammals upon administration of mutated ferritin that is expressed in bacteria or yeast.
Thus, it would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have mutated the ferritin of Schwendt et al to inhibit formation of a N-glycan, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Nabel et al disclose a mammal exposed to a glycosylated protein produced in bacteria or yeast may generate an immune response to the glycosylated protein, because the pattern of glycosylation of a given protein in bacterial or yeast could be different from the pattern of glycosylation of the same protein in a mammal. Thus, mutating the ferritin to inhibit formation of a N-glycan reduces an anti-nanocage monomer peptide immune response.
Response to Applicant’s Argument
Applicants states that the immunogenic peptide excludes the C-terminal Domain of PfCSP. This is not found persuasive. “C terminal domain” does not convey an particular C terminal domain sequence of PfCSP. The protein of Schwendt et al does not comprise a C terminal domain sequence of PfCSP and thus meets the limitation of excludes the “C terminal Domain”. Applicant can obviate this issue by reciting which residues of PfCSP are excluded. Limitations from the specification are not read into the claims and the instant specification does not specifically define “C terminal domain of PfCSP.
Even if the residues covering “C terminal Domain” are recited, this is with regards to the immunogenic peptide. The fusion protein of Schwendt et al will still be regarded as an immunogenic variant thereof.
The rejection of claim(s) 1 and 20 under 35 U.S.C. 103 as being unpatentable over Daubenberger et al. WO2018193063 10/25/2018 filed 4-19-2018 in view of Nabel et al. WO 2019/195316 10/10/19 filed 4/2/19 is maintained.
Claim 1: Daubenberger et al disclose an immunogenic fusion protein comprising:
an immunogenic peptide or an immunogenic variant thereof, the immunogenic peptide comprising NPDPb and NANPc (p. 18 SEQ NO: 5, 6);
an immunogenic peptide or an immunogenic variant thereof, the immunogenic peptide comprising NPDPb and NANPc (p. 19-p. 22, SEQ ID NO: 7-23) or
wherein a=1, b=1, c is greater than 0, d=0 and e is greater than 0 and wherein a+b+c+d+e is at least 2; and
a nanocage monomer peptide such as ferritin, sulfur oxygenase reductase (SOR), lumazine synthase, and pyruvate dehydrogenase. See p. 36 lines 9-31.
See p. 12, p. 22-23 and p. 26-27.
Daubenberger et al does not disclose the nanocage monomer peptide ferritin is modified to reduce an anti-nanocage monomer peptide immune response.
Nabel et al disclose ferritin nanoparticles for use in immunization (paragraph 209), wherein the ferritin comprises a mutation to inhibit formation of a N-glycan (paragraph 286). Nabel et al disclose a mammal exposed to a glycosylated protein produced in bacteria or yeast may generate an immune response to the glycosylated protein, because the pattern of glycosylation of a given protein in bacterial or yeast could be different from the pattern of glycosylation of the same protein in a mammal. Thus, some glycosylated therapeutic proteins may not be appropriate for production in bacteria or yeast. See paragraph 288. Nabel at [00289] disclose that decreased glycosylation ferritin by amino acid mutation facilitates protein production in bacteria or yeast. In some embodiments, decreased glycosylation of ferritin reduces the potential for adverse effects in mammals upon administration of mutated ferritin that is expressed in bacteria or yeast.
Thus, it would have been prima facie obvious to a person of ordinary skill in the as of the effective filing date to mutated the ferritin of Daubenberger et al to inhibit formation of a N-glycan, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Nabel et al disclose a mammal exposed to a glycosylated protein produced in bacteria or yeast may generate an immune response to the glycosylated protein, because the pattern of glycosylation of a given protein in bacterial or yeast could be different from the pattern of glycosylation of the same protein in a mammal. Thus, mutating the ferritin to inhibit formation of a N-glycan reduces an anti-nanocage monomer peptide immune response.
Response to Applicants Argument
Applicants argument that the reference fails to exclude the C terminal domain of PfCSP and fails to teach specific motifs has been carefully considered but is not found persuasive. Even if “C terminal Domain of PfCSP” are excluded, this is with regards to the immunogenic peptide. The fusion protein of Daubenberger et al et al will still be regarded as an immunogenic variant thereof. Regarding claim 37, the immunogenic peptide of Daubenberger et al is a functional variant or fragment thereof of SEQ ID NO: 26-30 e.g. See SEQ ID NO: 5-23 of Daubenberger et al.
New Claim Rejections
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.
Claims 1, 5, 11, 13, 15-17, 19-20, 26, 28, 29, 36, 37, and 41 are 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.
The metes and bounds of “C-terminal domain of PfCSP” is vague and indefinite. This term is not defined in the specification. It is not clear what residues are included and excluded from the “C-terminal domain of PfCSP”.
In claim 36, the sequence for SEQ ID NO: 36 in the sequence listing does not match the sequence for SEQ ID NO: 36 in the claims.
In claim 36, the sequence for SEQ ID NO: 37 in the sequence listing does not match the sequence for SEQ ID NO: 37 in the claims.
Applicants assistance is requested to check that all sequences set forth in the claims match what is in the sequence listing for the respective SEQ ID Nos.
Status of Claims
Claims 1,5, 11, 13, 15-17, 19-20, 26, 28-29, 36-37 and 41 are rejected. Claims 64 and 67-68 are withdrawn. Claim 25 is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645