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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/4/2026 has been entered.
Claims 4-5, 10-11, 13-15 and 18-19 are cancelled. Claim 1 has been amended. Claims 1-3, 6-9, 12, 16-17 and 20-21 are pending and are under examination.
Claim Rejections Withdrawn
The rejection of claims 1-3, 6, 12 and 20 under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more is withdrawn in view of the amendment to claim 1.
The rejection of claim(s) 1-3, 6, 12 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Database Uniprot Accession number A0A1W6ZED7 July 5, 2017 as evidenced by Bordetella genomosp. 13 AU7206 retrieved from https://img.jgi.doe.gov/cgi-bin/m/main.cgi?section=TaxonDetail&page=taxonDetail&taxon_oid=2765235881 12-20-2017 and as evidenced by Accession number CP021111 REGION: 3571008..3571598 of Bordetella genomosp. 13 strain AU7206 chromosome, complete genome
GenBank: CP021111.1 5-19-2017 is withdrawn in view of the amendment to claim 1.
Claim Rejections - 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The rejection of claim(s) 1-3 under 35 U.S.C. 102(a)(1) as being anticipated by Database Uniprot A0A1C3K890 Nov 2, 2016 is maintained.
Database Uniprot A0A1C3K890 discloses a polypeptide which comprises a sequence having 84.2% sequence identity with SEQ ID NO: 1 with a substitution at I126T in an OmpA-like domain. See sequence alignment below with a query of SEQ ID NO: 1 with D124N substitution. Said polypeptide meets the structural limitations of the claims including the mutations in the OmpA-like domain and thus would necessarily also increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
See sequence alignment below with a query of SEQ ID NO: 1 with D124N substitution.
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450
888
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Response to Applicant’s Argument
Applicant argues that the mutant polypeptide is directed to a different bacterial Orrella dioscoreae while the claims are drawn to mutant Borrelia polypeptide.
Applicants argument has been carefully considered but is not found persuasive.
This is because “Bordetella” in “a mutant Bordetella polypeptide” does not serve to structurally distinguish the polypeptide from the polypeptide disclosed in Database Uniprot A0A1C3K890. The polypeptide disclosed in Database Uniprot A0A1C3K890 meets the structural limitation of the claimed polypeptide regardless of the word “Bordetella”. “Bordetella polypeptide” is not defined in the specification to limit to those polypeptides isolated from Bordetella. The claims allows for substantial variability of at least 50% sequence identity with SEQ ID NO: 1. SEQ ID NO: 1 is the amino acid sequence of Bordetella OmpA (see p. 13 lines 30-32). When 50% of SEQ ID NO: 1 can vary e.g. by substitution, deletion or insertion or combinations thereof, the resulting protein is substantially different from SEQ ID NO: 1 from Bordetella. Thus, “Bordetella” in “a mutant Bordetella polypeptide” does not serve to structurally distinguish the “mutant Bordetella polypeptide” polypeptide from the polypeptide disclosed in Database Uniprot A0A1C3K890.
In addition, the polypeptide disclosed in Database Uniprot A0A1C3K890, meets the structural limitations of claim 1 and thus will necessarily have the same properties recited in the intended use to increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Moreover, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
The rejection of claim(s) 1-3 under 35 U.S.C. 102(a)(1) as being anticipated by Rahmah et al. SG158788-A1 02-26-2010 is maintained.
Rahmah et al disclose a polypeptide comprising a sequence having at least 50% sequence identity with SEQ ID NO: 1 and comprising a substitution mutation in an OmpA-like domain, wherein the substitution mutations are located at the following position corresponding to SEQ ID NO: 1: S125R, H122Y, and V120T. Said polypeptide meets the structural limitations of the claims including the mutations in the OmpA-like domain and thus would necessarily also increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
See sequence alignment below with a query of SEQ ID NO: 1 with D124N substitution.
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999
618
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Response to Applicant’s Argument
Applicant argues that the mutant polypeptide is directed to a different bacteria Burkholderia pseudomallei Outer Membrane Protein A (OmpA) while the claims are drawn to mutant Borrelia polypeptide.
Applicants argument has been carefully considered but is not found persuasive.
This is because “Bordetella” in “a mutant Bordetella polypeptide” does not serve to structurally distinguish the polypeptide from the polypeptide disclosed by Rahmah et al. The polypeptide disclosed by Rahmah et al. meets the structural limitation of the claimed polypeptide regardless of the word “Bordetella”. “Bordetella polypeptide” is not defined in the specification to limit to those polypeptides isolated from Bordetella. The claims allows for substantial variability of at least 50% sequence identity with SEQ ID NO: 1. SEQ ID NO: 1 is the amino acid sequence of Bordetella OmpA (see p. 13 lines 30-32). When 50% of SEQ ID NO: 1 can vary e.g. by substitution, deletion or insertion or combinations thereof, the resulting protein is substantially different from SEQ ID NO: 1 from Bordetella. Thus, “Bordetella” in “a mutant Bordetella polypeptide” does not serve to structurally distinguish the “mutant Bordetella polypeptide” polypeptide from the polypeptide disclosed in Rahmah.
In addition, the polypeptide disclosed in Rahmah meets the structural limitations of claim 1 and thus will necessarily have the same properties recited in the intended use to increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Moreover, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
The rejection of claim(s) 1-3 under 35 U.S.C. 102(a)(1) as being anticipated by Paas et al. WO2011125015 13-10-2011 is maintained.
Paas et al disclose a polypeptide comprising a sequence having at 90.9% sequence identity with SEQ ID NO: 1 and comprising a substitution mutation in an OmpA-like domain, wherein the substitution mutation is located at the following position corresponding to SEQ ID NO: 1: H122N. Said polypeptide meets the structural limitations of the claims including the mutation in the OmpA-like domain and thus would necessarily also increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
See sequence alignment below with a query of SEQ ID NO: 1 with D124N substitution:
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1022
499
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Response to Applicant’s Argument
Applicant argues that the mutant polypeptide is directed to a different bacteria Citrobacter Koseri Outer Membrane Protein A (OmpA) while the claims are drawn to mutant Borrelia polypeptide.
Applicants argument has been carefully considered but is not found persuasive.
This is because “Bordetella” in “a mutant Bordetella polypeptide” does not serve to structurally distinguish the polypeptide from the polypeptide disclosed by Paas. The polypeptide disclosed by Paas meets the structural limitation of the claimed polypeptide regardless of the word “Bordetella” in “a mutant Bordetella polypeptide”. “Bordetella polypeptide” is not defined in the specification to limit to those polypeptides isolated from Bordetella. The claims allows for substantial variability of at least 50% sequence identity with SEQ ID NO: 1. SEQ ID NO: 1 is the amino acid sequence of Bordetella OmpA (see p. 13 lines 30-32). When 50% of SEQ ID NO: 1 can vary e.g. by substitution, deletion or insertion or combinations thereof the resulting protein is substantially different from Bordetella OmpA SEQ ID NO: 1. Thus, “Bordetella” in “a mutant Bordetella polypeptide” does not serve to structurally distinguish the “mutant Bordetella polypeptide” polypeptide from the polypeptide disclosed in Paas.
In addition, the polypeptide disclosed in Paas meets the structural limitations of claim 1 and thus will necessarily have the same properties recited in the intended use to increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Moreover, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
New Claim Rejections
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 1-3, 6-9, 12, 16-17 and 20-21 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. This is a written description rejection.
A mutant Bordetella polypeptide comprising a sequence having at least 50% sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at a position corresponding to any one of positions 120-127 SEQ ID NO: 1, and wherein the polypeptide comprising the mutation increases OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Thus, the claims are drawn to a large genus comprising numerous species highly variant from each other. The species can be generated by substitution, deletion and/or insertion and up to 50% of the sequence of SEQ ID NO: 1 can vary. Additional variation exists since there is mutation (insertion, substitution, deletion or combinations thereof) located at a position corresponding to any one of positions 120-127 in SEQ ID NO: 1.
The claim requires that members of the genus have the property of increasing OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
The specification describes an actual reduction to practice of D124N substitution mutation in B. pertussis OmpA (SEQ ID NO: 1) which resulted in viable cells and increased OMV. The specification teaches that the same substitution at the corresponding location D50N in the homolog OmpA homolog Bp2019 not have any effect on OMV production and the substitution at the corresponding location (D100N) in the homolog BP3342 appeared to be lethal. See section 2.2.1
The specification does not describe other members of the genus that have the property of increasing OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
The specification does not describe the common structure of the genus that correlates with property of increasing OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
There are no sufficient identifying characteristics of other representative members of the genus of variants that possess the functional property.
It is unpredictable from the disclosure of the D124N mutation in SEQ ID NO: 1 that other members of the large and variant genus will possess the functional property. The specification teaches that the same D124N substitution at the corresponding location D50N in the homolog OmpA homolog Bp2019 did not have any effect on OMV production and the substitution at the corresponding location (D100N) in the homolog BP3342 appeared to be lethal. In addition, Applicants in their reply on page 5 last paragraph state that mere structural similarity does not establish functional equivalence.
Even though one could screen for the variants that have the functional property, the courts have held that possession of a genus may not be shown by describing how to obtain members of the claimed genus or how to identify their common structural features. The written description requirement is separate and distinct from the enablement requirement (See also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) and adequate written description requires more than a mere reference to a potential method for identifying candidate mutant Bordetella polypeptides that have the functional property.
The purpose of the written description requirement is broader than to merely explain how to ‘make and use’ [the invention] Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111, 1114 (Fed. Cir. 1991). In an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See Noelle v Lederman. 355 F. 3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) and In re Alonso (Fed. Cir. 2008-1079).
In the instant case, Applicants have not described a sufficient number of variants having the functional property and represent the entire genus. The disclosure of D124N SEQ ID NO: 1 substitution mutant is insufficient to describe the entire genus of mutant Bordetella polypeptides comprising a sequence having at least 50% sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at a position corresponding to any one of positions 120-127 SEQ ID NO: 1, and wherein the polypeptide comprising the mutation increases OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
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 1-3, 6-9, 12, 16-17 and 20-21 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.
Claim 1 is drawn to a mutant Bordetella polypeptide comprising a sequence having at least 50% sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at a position corresponding to any one of positions 120-128 in SEQ ID NO: 1, and wherein the polypeptide comprising the mutation increases OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
The metes and bounds of “wherein said Bordetella is otherwise identical” is vague and indefinite. It is not clear in what way the Bordetella is otherwise identical and which Bordetella are being compared?
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 6, 12 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
The claim(s) recite(s):
Claim 1: A mutant Bordetella polypeptide comprising a sequence having at least 50% sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at a position corresponding to any one of positions 120-128 in SEQ ID NO: 1, and wherein the polypeptide comprising the mutation increases OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Claim 2: A polypeptide according to claim 1, wherein the mutation is a mutation of a single amino acid residue.
Claim 3: A polypeptide according to claim 1, wherein the mutation is a substitution of an amino acid residue.
The claimed polypeptide encompass a natural variant of OmpA as evidenced by Gentry-Weeks et al. J. Bacteriol. 174, 7729-7742, 1992 and PIR_80 Database Accession number A45275 11/18/1994 which discloses the amino acid sequence of a OmpA wild type variant sequence having 93% sequence identity with SEQ ID NO: 1 with a substitution H122N in an OmpA-like domain. PIR_80 Database Accession number A45275 discloses the Bordetella avium that comprises the genomic modification in the amino acid sequence of a OmpA polypeptide having a sequence having 93% sequence identity with SEQ ID NO: 1 with a substitution H122N in an OmpA-like domain, wherein the genomic modification results in expression of said OmpA polypeptide. See Appendix B.
The claimed polypeptide also encompasses a natural variant of OmpA as evidenced by Gentry-Weeks et al disclose OmpA of Bordetella sp. 2513F-2 wherein the OmpA is annotated as NCBI Reference Sequence: WP_459617982.1 which discloses a mutant Bordetella polypeptide comprising a sequence having at 88% sequence identity sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at position 126 i.e. I to T single amino acid residue substitution within the position corresponding to 120-127 in SEQ ID NO: 1. See Appendix C.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-3, 6, 12 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gentry-Weeks et al. J. Bacteriol. 174, 7729-7742, 1992 and PIR_80 Database Accession number A45275 11/18/1994.
Claims 1-3: Gentry-Weeks et al disclose OmpA of Bordetella avium wherein the OmpA is annotated as accession number A45275 which discloses a mutant Bordetella polypeptide comprising a sequence having at least 50% sequence identity i.e. 93% sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at position 122 i.e. H to N single amino acid residue substitution within the position corresponding to 120-127 in SEQ ID NO: 1. Said polypeptide meets the structural limitations of the claims including the mutations in the OmpA-like domain and thus would necessarily also increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Claim 6: Gentry-Weeks et al disclose discloses the Bordetella avium comprising a genomic modification corresponding to a mutation in an OmpA-like domain, wherein the mutation is located at position 122 i.e. H to N single amino acid residue substitution within the position corresponding to 120-127 in SEQ ID NO: 1 (accession number A45275). Since the Bordetella meets the structural limitation of claim 6, said genomic modification would also result in the expression of the polypeptide as defined in claim 1.
See sequence alignment in Appendix B.
Claim(s) 1-3, 6, 12 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gentry-Weeks et al. J. Bacteriol. 174, 7729-7742, 1992 as evidenced by NCBI Reference Sequence: WP_459617982.1 1-30-2026.
Claims 1-3: Gentry-Weeks et al disclose OmpA of sp. 2513F-2 wherein the OmpA is annotated as NCBI Reference Sequence: WP_459617982.1 which discloses a mutant Bordetella polypeptide comprising a sequence having at 88% sequence identity sequence identity with SEQ ID NO: 1 and comprising a mutation in an OmpA-like domain, wherein the mutation is located at position 126 i.e. I to T single amino acid residue substitution within the position corresponding to 120-127 in SEQ ID NO: 1. Said polypeptide meets the structural limitations of the claims including the mutations in the OmpA-like domain and thus would necessarily also increase OMV production when expressed in Bordetella as compared to OMV production in a Bordetella expressing a polypeptide having SEQ ID NO: 1 and wherein said Bordetella is otherwise identical.
Claim 6: Gentry-Weeks et al disclose discloses the Bordetella sp. 2513F-2
comprising a genomic modification corresponding to a mutation in an OmpA-like domain, wherein the mutation is located at position 126 i.e. I to T single amino acid residue substitution within the position corresponding to 120-127 in SEQ ID NO: 1 (NCBI Reference Sequence: WP_459617982.1). Since the Bordetella meets the structural limitation of claim 6, said genomic modification would also result in the expression of the polypeptide as defined in claim 1.
See sequence alignment in Appendix C.
Status of Claims
Claims 1-3, 6-9, 12, 16-17 and 20-21 are rejected.
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/OLUWATOSIN A OGUNBIYI/Primary Examiner, Art Unit 1645
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