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 .
Claim status
Amendments filed 10/25/2024 are entered.
Claims 1, 47-49, 53, 62, 64-65 are pending and under examination.
Priority
The application is a 371 application, filed 07/19/2024, of PCT application PCT/AU2023/050030, filed 01/20/2023, which claims priority benefits from Foreign Application No. AU2022300103, filed 01/20/2022. The effective filing date of this application is 01/20/2022, the filing date of Foreign Application No. AU2022300103.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 10/24/2024 is being considered by the examiner.
Claim Objection
Claim 1 is objected to because of the following informalities:
Claim 1, part B) is directed to the second polypeptide and recites the domains and mutations required in this second polypeptide. However, there is inconsistency in when the bullet points ( i.e. a), b), and c)) are used. Some limitations have bullet points and others do not. The domains ABM and CAD limitations are not listed in bulleted form, but the domain DUF2436 limitation is. The two required types of mutations (cysteine substitution and motif mutation) are bulleted. Secondly, between the two required mutations, bullet points b) is indented more than c). These different formatting may lead of confusion. A suggested amendment is to be at least consistent with how the required domains are formatted and how the required mutations are formatted, or both can be formatted consistently the same. For example, all could be bulleted appropriately.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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, 47-49, 53, 62, and 64-65 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 term “substantially” in claim 1 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what the boundaries are for an amino acid sequence corresponding substantially to the full length of the DUF2436 domain because it is unclear what the metric is to determine substantial, especially in light of the alternative limitation allowing for at least 80% sequence similarity.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1, limitation A) and B) recites the broad recitation that the first/second polypeptide “comprise”, and the claim also recites that the first/second polypeptide “consist” which is the narrower statement of the range/limitation. The claim continues to recite the second polypeptide “comprise”. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 47-49, 53, 62, 64-65 depend on claim 1 but do not resolve the indefiniteness of claim 1, as they do not distinctly define the sequence, and therefore inherit the indefiniteness.
Further regarding claim 65, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05 (c) - (d).
Claim Rejections - 35 USC § 112(a)
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 64 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 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 The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed.
CLAIMED INVENTION
Claim 64 is directed to an antibody preparation comprising an antibody directed to P. gingivalis, wherein the antibody preparation is obtained by administering the fusion protein of claim 1, which is a fusion protein comprising of the active site of an Arg- or Lys-gingipain of P. gingivalis and an adhesin domain of an Arg- or Lys-gingipain of P. gingivalis.
WHAT THE SPECIFICATION TEACHES
The specification is silent on the sequences of any of the claimed antibodies.
THE STATE OF THE ART REGARDING THE ELECTED INVENTION
The state of the art teaches an antibody sequence cannot be distinctly known solely by knowing what it binds to. The state of the art teaches that antibodies that bind the same antigen, and even the same epitope, can still have different sequences and different binding site structure in the absence of the antigen (Abstract; Nair et al, Epitope Recognition by Diverse Antibodies Suggests Conformational Convergence in an Antibody Response, The Journal of Immunology, published 2002). This is why distinct monoclonal antibodies, i.e. antibody of different sequences, can recognize a common epitope. Therefore, the exact sequence (i.e. structure) of the antibody that binds an epitope is not predictable only from the epitope and epitope sequence.
WHAT WRITTEN DESCRIPTION IS MET BY THE ELECTED INVENTION
The process to get the antibody preparation has written description support because the state of the art teaches how to prepare antibody preparations against an immunogen. The immunogen itself has written description support.
WHY THE INVENTION LACKS WRITTEN
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The disclosure does not provide full or partial structure for the antibody. The state of the art teaches that functional characteristics alone cannot lead to full structure for an antibody. There is no known or disclosed correlation between structure and the function of binding particular epitopes. There is no disclosed correlation between the method of making this product and the resultant structure.
Claim 64 is a product-by-process claim. The product itself, the antibody, must have written description. The structure of the antibody is not disclosed. Written description for an antibody is not met by disclosing what it binds, if the sequence is not already known in the art.
CONCLUSION
Claim 64 lacks written description because the structure of the antibody preparation cannot be determined solely by what it binds without any link relating structure and function.
Closest Prior Art
In summary, the combination of prior art teaches the chimeric proteins comprising of the first polypeptide fused to the ABM, CAD, and/or DUF2436 domain.
The prior art teaches the motivation for the cysteine substitution(s).
However, the prior art does not explicitly teach any of the three possible amino acid motif substitution. The prior art does not teach the importance of the specific residues being mutated in these sequence motif mutations. Furthermore, the instant specification discloses the individual or added benefits to protein solubility conferred by the amino acid motif substitutions compared to the cysteine substitutions alone (Table 2).
The prior art teaches the method of producing these proteins using a host cell comprising of a vector that comprises of the nucleic acid encoding a chimeric protein for inducing an immune response to P. gingivalis, but not the instantly claimed chimeric protein.
The prior art teaches a method for obtaining an antibody directed to a chimeric protein for inducing an immune response to P. gingivalis, but not the instantly claimed chimeric protein.
The prior art teaches a kit comprising of a chimeric protein for inducing an immune response to P. gingivalis, but not the instantly claimed chimeric protein.
O’Brien-Simpson, et al, A therapeutic Porphyromonas gingivalis gingipain vaccine induces neutralising IgG1 antibodies that protect against experimental periodontitis, Npj Vaccines, published 2016.
O’ Brien-Simpson teaches a fusion protein for inducing an immune response to P. gingivalis comprising of
a first polypeptide that comprise of the amino acid sequence of the active site of a Lys-gingipain of P. gingivalis, or a sequence that is at least 80% identical thereto, referred to as KAS (specifically, KAS1 and KAS2), and
a second polypeptide comprising of an amino acid sequence of an adhesin domain of an Arg- or Lys-gingipain of P. gingivalis, referred to as KgpA1 or A1. This adhesin domain comprises one or more ABMs (specifically comprises of ABM1, ABM2, and ABM3), a truncated CAD domain, and a DUF2436 domain (Supplemental Figure 2(a)).
O’ Brien-Simpson further teaches a method of inducing an immune response in a subject to P. gingivalis and a method for obtaining an antibody directed to P. gingivalis, the method comprising administering to a subject and to a non-human animal, in need thereof, a chimeric or fusion protein (p. 16022; section: Protective efficacy of the KAS2-A1 chimera in a therapeutic vaccination periodontitis model). This would therefore produce an antibody preparation directed to P. gingivalis, but does not teach the exact antibody because the fusion protein is different.
O’ Brien-Simpson teaches a kit comprising of the chimeric or fusion protein, which is an antigen (p. 6, lines 29-30).
O’ Brien-Simpson further teaches producing these proteins using a host cell comprising of a vector that comprises of the nucleic acid encoding a chimeric protein for inducing an immune response to P. gingivalis, but not the instantly claimed chimeric protein.
Furthermore, the DUF2436 domain is not the full length nor at least 80% identical to the full-length sequence. The DUF2436 domain is a truncated form of DUF2436 (Supplemental Figure 2(a) and matches with instant SEQ ID NO: 13, which does not match the claim limitation.
O’ Brien-Simpson does not explicitly teach purifying the antibody produced against the fusion protein.
O’ Brien-Simpson also does not explicitly teach either of the claimed mutations.
Reynolds et al, WO 01/47961 A1, filed 12/21/2000
Reynolds teaches a fusion protein for inducing an immune response to P. gingivalis comprising a
a first polypeptide that comprise of the amino acid sequence of the active site of an Arg-gingipain of P. gingivalis, and
a second polypeptide comprising of an amino acid sequence of an adhesin domain comprising of the ABM, CAD, and DUF domains (SEQ ID NO: 3), and
cysteine mutations in the adhesin domain to serine or alanine could further enhance the protein stability because the cysteines can form disulfide bonds that may lead to incorrect folding, leading to insoluble proteins (p. 19, lines 4-9).
Reynolds does not explicitly teach the amino acid motif mutations.
Yasaki-Inagaki et al, Production of protective antibodies against Porphyromonas gingivalis strains by immunization with recombinant gingipain domains; published 2005
Yasaki-Inagaki teaches a fusion protein comprising of the active site of an arginine gingipain (Rgp CAT), a lysine gingipain (Kgp CAT), and an adhesin domain (p. 288, section: Preparation of recombinant gingipains).
Yasaki-Inagaki teaches purification of the antibodies against this fusion protein (p. 290, section: Purification of antirecombinant gingipain domain antibodies).
Yasaki-Inagaki also does not explicitly teach the amino acid motif mutations.
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, 47-49, 53, 62, 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-100 of claims filed 04/28/2025 of copending Application No. 18730619 in view of O’Brien-Simpson et al (A therapeutic Porphyromonas gingivalis gingipain vaccine induces neutralising IgG1 antibodies that protect against experimental periodontitis, Npj Vaccines, published 2016).
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 18730619 (App. ‘619) claims the fusion protein for inducing an immune response to P. gingivalis comprising of all the domains and mutations instantly claimed, except for a sequence of a cleaved adhesin domain (CAD). App. ‘619 also claims the nucleic acid encoding this fusion protein and the vector comprising this nucleic acid. App. ‘619 also claims a method for immunizing a subject with the claimed fusion protein, a method for obtaining an antibody directed to the fusion protein, and the antibody preparation against P. gingivalis from administering the fusion protein.
However, O’ Brien-Simpson teaches a fusion protein for inducing an immune response to P. gingivalis comprising of the CAD sequence. Specifically, the fusion protein comprises of:
a first polypeptide that comprise of the amino acid sequence of the active site of a Lys-gingipain of P. gingivalis, or a sequence that is at least 80% identical thereto, referred to as KAS (specifically, KAS1 and KAS2), and
a second polypeptide comprising of an amino acid sequence of an adhesin domain of an Arg- or Lys-gingipain of P. gingivalis, referred to as KgpA1 or A1. This adhesin domain comprises one or more ABMs (specifically comprises of ABM1, ABM2, and ABM3), a truncated CAD domain, and a DUF2436 domain (Supplemental Figure 2(a)).
O’ Brien-Simpson further teaches a method of inducing an immune response in a subject to P. gingivalis and a method for obtaining an antibody directed to P. gingivalis, the method comprising administering to a subject and to a non-human animal, in need thereof, a chimeric or fusion protein (p. 16022; section: Protective efficacy of the KAS2-A1 chimera in a therapeutic vaccination periodontitis model). This would therefore produce an antibody preparation directed to P. gingivalis.
It would have been obvious to one skilled in the art that the CAD domain could be added to this fusion protein as an additional epitope region as an alternative fusion protein for inducing an immune response to P. gingivalis in light of O’ Brien-Simpson’s teaching of the fusion protein comprising it, serving the same purpose as App ‘619.
One skilled in the art, before the effective filing date of the instant application, would be motivated to include an additional epitope site to increase the potential antibody response.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to O’ Brien-Simpson’s teaching a sequence of the CAD in an immunogenic fusion protein with the other domains claimed in App ‘619. Therefore, the addition of CAD is compatible with the fusion protein of App ‘619.
Conclusion
No claims are allowed.
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/BONIRATH CHHAY/Examiner, Art Unit 1645 Friday, June 26, 2026
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 29, 2026
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