DETAILED ACTION
The Office action mailed 3-18-26 is hereby withdrawn and a new Office action is set forth below.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 1-20-26.
Claims 31, 52-61 are pending in the instant application.
Election/Restrictions
Claims 1, 2, 6, 10, 13, 14, 19, 20 have been canceled and are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1-20-26
Applicant’s election without traverse of Group V, claims 31, 52-61, the combination of peptides EsxA (Rv3875), EspC (Rv3615c), TB22.2 (Rv3036c), Rv0383c, and PE25-PPE41 (Rv2431c/Rv2430c), in the reply filed on 1-20-26 is acknowledged.
Sequence Non-Compliance
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Please provide information for the sequences disclosed on pages 245-246 of the figures.
Please provide SEQ ID Nos. for the peptides disclosed in the specification, figures and/or claims, where appropriate.
Specific deficiency –
This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because no sequence listing has been provided for this application. Antisense molecules are recited in the claim and specification, but no corresponding sequences or accompanying SEQ ID Nos. have been provided (see, e.g., claim 9, line 2).
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
Claim Objections
Claim 55 is objected to because of the following informalities: Claim 35, line 2, recites “five peptides”, but claim 31 recites “six peptides”. Appropriate correction is required.
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 31, 52-61 are rejected 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 products of nature without significantly more. The claim(s) recite(s) products of nature including EsaA. This judicial exception is not integrated into a practical application because they recite products of nature. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they recite compositions comprising products of nature. He 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 non-statutory subject matter. The claimed invention is directed to products of nature comprising compositions of an inoculum or a vehicle comprising EsxA, EspC, TB22.2, Rv0383c, PE25, and PPE41 or a nucleic acid or nucleic acids encoding each of the peptides. These peptides are naturally occurring peptides of Mycobacterium tuberculosis (see attached NCBI data on esxA obtained from Mycobacterium tuberculosis H37Rv). The claims do not include any elements that add significantly more to any judicial exceptions, and do not include features that demonstrate that the recited products are markedly different from what exists in nature. The fragments perform in their natural way, serve the ends nature originally provided, and act quite independently of any effort of patentee. There are no marked differences in the function or structure of these naturally occurring molecules, and their characteristics do not change from that occurring in nature.
In sum when the relevant factors are analyzed, they weigh toward ineligibility under 35 U.S.C. 101. Therefore, the claims are non-statutory, and the rejection under 35 U.S.C. 101 is appropriate.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 31, 52-61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lou et al (Molecular Microbiology, Vol. 103, No. 1, pages 26-38 (2017)), Korotkova et al (Mol. Microbiol. Viol 94, No. 2, pages 367-382 (2014)), Ma et al (J. Biol. Chem. Vol. 290, No. 11, pages 7314- (2015)), Guo et al (Emerging Microbes and Infections, Vol. 10, pages 19-36 (2021)), the combination in view of Lewinsohn et al (US 2017/0028048).
The claims are drawn to a vaccines or pharmaceutical formulations for providing immunity against a Mycobacterium tuberculosis complex (MTBC) infection comprising an immunologically protective dose of an inoculum or a vehicle comprising EsxA, EspC,TB22.2,Rv0383c,PE25, and PPE41 or (b) a nucleic acid or nucleic acids encoding each of the peptides, optionally formulated for oral, intrathecal, topical, rectal, subdural, intravenous, intranasal, aerosol, or intramuscular delivery (IM), administration, which peptides or nucleic acid or nucleic acids are optionally contained in or on, or expressed on, or carried in a nanoparticle, a particle, a micelle or a liposome or lipoplex, a polymersome, a polyplex, a phage or a dendrimer, which peptides or nucleic acid or nucleic acids are formulated as, or contained in or expressed on: a tablet, a pill, a capsule, a gel, a geltab, a liquid, a powder, an emulsion, a lotion, an aerosol, a spray, a lozenge, an aqueous or a sterile or an injectable solution, or an implant, which nucleic acid or nucleic acids are optionally contained in an expression cassette, vector, plasmid, phagemid, a chimeric genetically engineered phage, or artificial chromosome.
Lou et al (Molecular Microbiology, Vol. 103, No. 1, pages 26-38 (2017)) teach the mediation by the Esx1 secretion system, exporting EsxA and EsxB for co-secretion. Pathogenicity of mycobacterium tuberculosis is mediated by EsxA and EsxB, and major virulence factors co-secreted with Esp A and EspC. The C-terminal domain is required for multimerization as truncation and point mutations impact Espc filament formation and reduce secretion of EsxA, causing attenuation of M. tb. Espc thus serves as either a modulator of Esx1 function, or as a component of the secretions apparatus (see esp. the Summary and Introduction on pages 26-27). Lou teaches the expression of the EspC protein in pathogenic mycobacteria (page 28, second full paragraph). Lou teaches EspC binding to EspA and the secretion from M. tb.(Fig. 2 on page 29).
Korotkova et al (Mol. Microbiol. Viol 94, No. 2, pages 367-382 (2914)) teach the necessity of pe25 and PP41 in their dimerization and proper structure for secretion. This Esx system is critical for virulence mechanisms. The PE and PPE proteins carry functional domains and are associated with virulence and persistence in the host Pe and PPE proteins are highly abundant in pathogenic mycobacteria (see page 2, text in the introduction).
Ma et al (J. Biol. Chem. Vol. 290, No. 11, pages 7314- (2015) teach the role of EsxA as an important virulence factor for Mycobacterium tuberculosis, exhibiting a unique membrane interacting activity in Mycobacterium tuberculosis. The carboxy and amino termini of EsxA are required for membrane insertion. The central helix-turn-helix motif of EsxA forms a membrane spanning pore (see esp. the text on pages 7314-7315). EsxA is a potent T-cell antigen and is an important virulence factor in tuberculosis infection (see Discussion on page 7318).
Guo et al (Emerging Microbes and Infections, Vol. 10, pages 19-36 (2021)) teach EspC as being essential for mycobacterium tuberculosis host interactions and in spreading infection. EspC induced ER stress mediated apoptosis and may be employed by mycobacterium tuberculosis to establish and spread infection. EspC is a critical virulent factor that mediates mycobacteria tuberculosis-macrophage interactions by triggering endoplasmic reticulum stress-mediated apoptosis and promoting mycobacterial infection. EspC mediated ER stress is associated with generation of proinflammatory cytokines (see esp. the Abstract and Introduction on pages 19, 20; Fig. 2 on page 25).
The primary references do not teach the antigen Rv0383c, viral vectors or recombinant plasmids, tablets, pills, or liposomes, etc. claimed.
Lewinsohn et al (US 2017/0028048) teach the mycobacterial tuberculosis (Mtb) antigen Rv0383c for clinical validation studies (see Table 2). Lewinsohn teaches viral vectors, and plasmids for the expression of one or more mycobacterium tuberculosis polypeptide for treating mycobacterium tuberculosis. Lewinsohn teaches compositions comprising Mtb polypeptides in vectors and in liposomes or micelles (see esp. para 0035, 0085, 0145, 0153, 0157, 0159-0161, 0168).
It would have been obvious to provide a compositions comprising the mycobacterial tuberculosis (Mtb) antigens EsxA, EspC,TB22.2,Rv0383c,PE25, and PPE41 or a nucleic acid or nucleic acids encoding each of the peptides for treating Mtb because these antigens were well known in the art for their involvement in Mtb infectivity, as taught previously by Lou, Korotkova, Ma, Guo and Lewinsohn. One would have been motivated to provide the composition comprising these antigens for generating an immune response against Mtb. One of ordinary skill would have reasonably expected this combination of antigens to immunologically challenge Mtb infections in a host. For these and the aforementioned reasons, the instant invention would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application.
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Jane Zara
3-24-26
/JANE J ZARA/Primary Examiner, Art Unit 1637