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 .
The response and amendment to the claims filed 3-12-2026 has been entered
Status of Claims
Claims 1, 2, 3, 5, 8, 10, 11, 25-30 and 39-42 are pending.
Election/Restrictions
Applicant’s election of Group I (claims 1-3, 5, 8, 10, 11, 25, 26, 27 and 28) in the reply filed on 3-12-2026 is acknowledged. Applicant also elected the species (a) the combination of LIC_12985 and LIC_12340, or a conserved ortholog thereof having at least 99% sequence identity to LIC_12985 and LIC_12340; and (b) a bacterial target. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The Office notes the request for rejoinder of method claims 39 and 40 in the event that the allowance of the product claims.
Information Disclosure Statement
The information disclosure statements filed 1-23-25, 3-13-206 and 4-16-26 have been considered. Initialed copies are enclosed.
Claim Rejections - 35 USC § 112
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(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.
Claims 1-3, 5, 8, 10, 11 and 25-28 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claim 1 and dependent claims, the claims recite the terms “LIC_12985, LIC_12340, LA_3490, LA_0620, and LA_1402” which are genetic loci in a particular database that are subject to updates and changes. The genetic loci are not protein sequences and the sequences derived from genes are subject to changes in the database. As such, reference to the gene loci and not the specific protein sequence renders the scope of the claim indefinite. Additionally, the claims recite that a protein ortholog having at lease 99% identity to the gene loci is likewise indefinite. All claims dependent on the independent claim likewise lack clarity as they do not unambiguously resolve the structure of the VM protein.
Additionally, claim 1 and dependent claims recite fragments of the proteins comprising the DNase domain selected from one of the same. The specification describes that the full-length recombinant proteins have DNase activity. The specification describes that the C-terminal of the VM proteins has the DNase activity, that the metes and bound of the “domain” is not set forth. C-terminal does not define the specific residues in the VM proteins that is consider the DNase domain. Alignments provided a structural resemblance in the active site but structural similarity was low outside of the predicted active site (see page 143, lines 9-19). This does not specify what the metes and bounds of the domain are (i.e. the specific residues on the proteins that comprise the domain). As such, the skilled artisan would be unable to ascertain the metes and bounds of the DNase domain fragment as claimed.
As to claims 2,3,10 and 11 lack clear antecedent basis to claim 1, the claim should reference “the VM protein” etc.
As to claim 5, the claim metes and bounds are unclear as it further comprises elements already present in claim 1. Clarification is requested.
As to claim 8, the claim lacks proper antecedent basis to claim 5 as it does not relate the claimed sequences to particularly any particularly recited VM proteins. Therefore, the claims lack clarity in how the sequences limit the structure of the composition.
As to claim 8, the claim is confusing in the recitation of VM proteins of SEQ ID NO:2, 4 or 8, because the sequences represent mCherry fusions with G4S linkers and an enterokinase cleavage site and not the VMs per se. These sequence numbers do not represent the proteins encoded by genetic loci LA_3490, 0620 or 1402 or 99% sequence identical variants or fragments comprising the DNase domain.
Claims 25 and 28 are rejected under 35 U.S.C. 112(d), 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. The claims recite where the composition comprises a vaccine/toxoid vaccine. This language is viewed as an intended use of the proteins of claim 1 and as such, does not properly further limit the composition of claim 1 since they do not provide additional physical elements to the composition of claim 1. 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 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, 5, 8, 25, 26 and 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to protein compositions without significantly more. The claim(s) recite(s) a composition comprising Leptosprial virulence modifying proteins or DNase domain fragment therefrom. This judicial exception is not integrated into a practical application because it is natural product which is non-statutory subject matter. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they are recited to a high level are well understood, routine and conventional.
The claimed invention is directed to non-statutory subject matter the claims are drawn to naturally occurring Leptospiral virulence modifying (VM) proteins or DNase domain fragments of the naturally occurring polypeptides in combination with other VM proteins. The VM polypeptides and fragments are naturally occurring. The polypeptides of the claims are not modified in any manner that confers a marked structural difference from the naturally occurring product. Even though the VM polypeptides DNase domain appear to be fragments of naturally occurring polypeptides, they are not markedly different. The newly described function of DNase activity is inherent in the polypeptide structure and is not the result of a modification to the polypeptide structure. Eligibility requires more than the hand of man, to be eligible the claimed product must be both non-naturally occurring and markedly different from naturally occurring product. In the instant case the claimed isolated polypeptide and fragment do not markedly structurally differ from that found in nature whose sequence comprise the claimed fragments. The removal of the isolated fragment from the intact naturally occurring polypeptide does not provide a marked structural difference of the fragment from that which is naturally occurring. The isolation of the polypeptide fragment does not confer a marked difference on the polypeptide per se. As such, the claimed product is not patent eligible see analgous rationale in Association for Molecular Pathology v Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013)) set forth for isolated nucleic acids. The claimed composition comprising the isolated polypeptide fragment does not meet the criteria as it merely combines the isolated polypeptide fragment with adjuvants that are naturally occurring such as CpG, cytokines and lipopolysaccharides. The term “recombinant” would also not confer a structural difference with respect to the naturally occurring polypeptide as the means of producing the polypeptide does not appear to confer a marked structural difference from the naturally occurring structure/sequence. With respect to the elements recited in addition to the judicial exception of a naturally occurring polypeptide or fragment thereof, the following is found: (1) it recited at a high level of generality such that substantially all practical applications of the judicial exception is covered and/or (2) it recites an element that is well understood, purely conventional or routine in the field of biotechnology. The claimed composition is also merely a combination of natural products (1) isolated recombinant VM protein or domain fragment and (2) an adjuvant. Funk Brothers Seed Co. v. Kalo Inoculant Co., 33 U.S. 127 (1948). Finally, the fusion of the DNase domain to the naturally occurring N-terminal targeting domain in the full-length protein does not distinguish the fused protein from that which is naturally occurring.
For the foregoing reasons, the claims are drawn to naturally occurring elements, alone or in combination that are not distinguishable from the naturally occurring elements and do not meet the requirements of 35 USC 101.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 5, 8 a), 25, 26 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lauretti-Ferreira et al (PLOS ONE, 19(3):e0230460, pages 1-16 published March 27, 2020).
Lauretti-Ferreira et al teach L. interrogans sv Copenhageni (ATCCTM BAA-1198) and the administration of heat-inactivated (Heat), LPS depleted with butanol (But), and LPS-depleted and inactivated with formaldehyde (ButFor) (see page 3, Materials and Methods).
The ATTCTM strain is inherently the strain Fiocruz L1-130 strain comprising the recited genetic loci identified herein as LIC_12985 and LIC_12340 and serovar Canicola orthologs as claimed.
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The Fiocruz L1-130 strain inherently comprises the claimed polypeptides and inherently contains gram negative compounds having known adjuvant activity (lipopolysaccharide) as provided in Lauretti-Ferreira et al. Additionally, the Heat, But or ButFor treatment would inherently produce toxoids. Lauretti-Ferreira et al teach bivalent vaccines comprising both the L1-130 strain and the ortholog strain Canicola. Therefore, the composition comprising VM proteins and fragments thereof compositions comprising targeting domains, adjuvants are inherent to the L1-130 strain provided as ATCCTM BAA-1198. Additionally, the bivalent vaccine combination provides for the combination of the two different serovar strains (see page 6, Table 2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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