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 10/3/25 has been entered. Claims 1, 9 and 24-25 have been amended.
Claims 1-2, 4, 9, 24-26, 28, 42, 71-72, 78 and 84-86 are pending. Claims 71-72, 78 and 84-86 are withdrawn. Claims 1-2, 4, 9, 24-26, 28 and 42 are under examination.
Information Disclosure Statement
The information disclosure statement filed 4/17/25 has been entered and an initialed copy is attached.
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:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - Withdrawn
The rejection of claim(s) 1-2, 9-11, 24-26 and 35 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Foerster et al. WO 2019/180080 9/26/2019 is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1, 4 and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Ainley et al. US 2008/0102079 May 1, 2008 is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1, 4, 9-11, 24-25, 28 and 35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bubeck-Wardenburg et al. US 2011/0027265 2/3/2011 is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1, 9-11, 25, 35, and 36 i under 35 U.S.C. 103 as being unpatentable over Foerster et al. WO 2019/180080 9/26/2019 in view of Taylor et al. US 2009/0053235 2/26/2009 cited in IDS is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1, 9-11, 25, 35, and 36 under 35 U.S.C. 103 as being unpatentable over Bubeck-Wardenburg et al. US 2011/0027265 2/3/2011 in view of Taylor et al. US 2009/0053235 2/26/2009 cited in IDS is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1, 9-11, 25, 35, and 42 under 35 U.S.C. 103 as being unpatentable over Foerster et al. WO 2019/180080 9/26/2019 in view of Foletti et al. J. Mol. Biol. 27 May 2013 Vol. 425, No. 10, p. 1641-1654 is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1, 9-11, 25, 35, and 42 under 35 U.S.C. 103 as being unpatentable over Bubeck-Wardenburg et al. US 2011/0027265 2/3/2011 in view of Foletti et al. J. Mol. Biol. 27 May 2013 Vol. 425, No. 10, p. 1641-1654 is withdrawn in view of the amendment to the claims.
Claim Rejections Based on Amendment
Claim(s) 1, 2, 9, 24, 25, 26 and 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Foerster et al. WO 2019/180080 9/26/2019 cited previously in view of Bubeck-Wardenburg et al. US 2011/0027265 2/3/2011 cited previously.
Foerster et al disclose a method of treating or preventing Staphylococcus genus bacteria and/or Staphylococcus genus bacteria related diseases in a subject in need thereof, the method comprising administering to the subject a composition comprising a modified hemolysin (Hla) prior to the subject/s first exposure to S. aureus, wherein the composition is administered to a mother of the subject (pregnant) while the subject is in utero.
Foerster et al disclose: “For immunization, a pregnant cow was immunized with 300 pg of recombinant mature S. aureus Hla H35L protein in PBS with Quil-A (Invitrogen, San Diego, USA) as adjuvant. S. aureus Hla comprising a H35L mutation was obtained by cloning, expressing in E. coli and purification as disclosed in Menzies and Kernodle, 1994 and Wardenburg & Schneewind 2008.”
See Foerster et al, page 37 under example 1.1.
The subject is in utero and thus has not been exposed to the bacterial pathogen.
Foerster et al disclose the bacterial antigen is Staphylococcus aureus alpha-hemolysin toxin with a substitution at the histidine at position 35 relative to SEQ ID NO: 1 with leucine (L), thereby abrogating functional pore formation by destabilizing the heptameric structure i.e. Hla H35L protein.
See p. 37 disclosing:
“In a highly preferred embodiment, the S. aureus Hla protein is a mutant form of S. aureus Hla according to UniProtKB/Swiss-Prot Database Entry No. P09616.2 which has reduced hemolytic activity. More preferably, the mutant is devoid of hemolytic activity. Within the context of the present invention, a protein is considered "devoid of hemolytic activity", when it does not possess a hemolytic activity in a hemolytic activity determination assay as published in Menzies and Kernodle, 1994. The publication Menzies and Kernodle, 1994, discloses mutant forms of the polypeptide according to amino acids 27 to 319 of the UniProtKB/Swiss-Prot Database Entry No. P09616.2 wherein the histidine in position 35, 48, 144 or 259 are substituted by leucine (mutants H35L, H48L, H144L and H259L). Mutants H48L, H144L and H259L exhibit a reduced hemolytic activity of 7, 16 and 46% and may be used as an S. aureus Hla protein according to the present invention. In a highly preferred embodiment of the present invention, the S. aureus Hla protein is a polypeptide according to SEQ ID NO: 1 which comprises a substitution of histidine 35 against leucine (H35L). According to Menzies and Kernodle, 1994, this mutant is devoid of hemolytic activity.”
Foerster et al disclose wherein the modified Hla comprises a substitution of a histidine amino acid at position 35 relative to SEQ ID NO: 1, wherein position 35 is substituted with any other amino acid, in the instant case leucine (L), thereby abrogating functional pore formation by destabilizing the heptameric structure. See portion of page 37 above.
Foerster et al does not disclose that the modified Hla comprises a substitution of amino acids at position 66 and 70 relative to SEQ ID NO: 1.
Bubeck-Wardenburg et al disclose an attenuated alpha-hemolysin (Hla) with a substitution(s) at position 24, 35, 66, 70, 110, and/or 152 relative to SEQ ID NO: 1 (the SEQ ID NO: 1 of Bubeck-Wardenburg et al is 100% identical to SEQ ID NO: 1). See table 1 for amino acid sequence of Hla. Examples of amino acid substitutions at the respective positions include H35L, R66C and E70C. See paragraph 24. Bubeck-Wardenburg et al disclose that these substitution(s) attenuate the toxin to make it functionally weaker or less toxic than an unaltered toxin. Bubeck-Wardenburg et al disclose that attenuated alpha-hemolysin is used in treating a disease or condition caused by a staphylococcus aureus pathogen, as well as prevention of or reduction in infection so as to prevent or minimize the extent of exposure to the pathogen. See paragraphs 12-18.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the method of Foerster et al by substituting the attenuated alpha-hemolysin with the attenuated alpha-hemolysin of Bubeck-Wardenburg et al, thus resulting in the instant invention with a reasonable expectation of success. Both attenuated alpha-hemolysins were known in the prior art and were known to have be less toxicity as compared to the unaltered alpha-hemolysin and both could be administered safely to a subject. Thus, the attenuated alpha-hemolysins could have been substituted and the results would have been predictable i.e. less toxicity and would have been suitable for the method of Foerster et al.
Regarding claim 9, since the combination of Foerster et al and Bubeck-Wardenburg et al disclose the same method step, the subject will also have reduced inactivation of T cells or reduced T cell suppression after administering the composition.
Claim(s) 4 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Foerster et al. WO 2019/180080 9/26/2019 and Bubeck-Wardenburg et al. US 2011/0027265 2/3/2011 as applied to claims 1, 2, 9, 24, 25, 26 and 42, further in view Thomas, Heather Smith (hereinafter “Thomas”). Developing a Pre-Weaning Vaccination Strategy. https://hereford.org/wp-ontent/uploads/2019/01/0119_VaccinationSchedule.pdf January 2019.
The combination of Foerster et al and Bubeck-Wardenburg et al is set forth above but does not disclose that the composition is administered to the subject one more times at birth after birth; (b) within about 1 , 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 minutes after birth; (c) within about 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24 hours after birth, (d) within about 1, 2, 3, 4, 5, 6, 7 days after birth, or (e) about 1, 2, 3, 4, 5, 6, 7, or 8 weeks after birth.
Thomas disclose that when cows are vaccinated during pregnancy antibodies are produced and included in the colostrum they produce and the “first milk” contains maternal antibodies that kick-start the calf’s immune system which is beneficial because the calves are prone to ingesting pathogens at birth from nursing a dirty udder or being born into a dirty environment.
Thomas et al disclose that if a calf ingests an adequate amount of colostrum within a few hours of birth, it gains instant immunity from antibodies. Thomas et al disclose that the immunity provided in the colostrum is temporary and weakens after a few weeks or months and calves must build their own immunities. Thomas et al disclose that the protection the calves receive at birth may not provide full protection and earlier vaccinations are becoming a norm in the industry to give calves an edge in the early stages of their lives.
Thomas et al disclose that giving calves vaccinations at two to three months of age has benefits about the time maternal antibody protection begins and the response to vaccination depends on how much maternal immunity is received at birth which can interfere with the response to the vaccine. See whole reference especially p. 1 and p. 2 left column paragraphs 1-5.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the method of the combination of Foerster et al and Bubeck-Wardenburg et al by additionally administering the composition at birth; minutes after birth within about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 45, 50, 55 minutes; within about 1-7 days after birth or about 1-8 weeks after birth, thus resulting in the instant invention with a reasonable expectation of success.
The teaching or suggesting or motivation (TSM) to do so is that Thomas disclose that levels of maternal antibodies present in a calves at birth may not be enough to be protective and in addition even when there is protective maternal immunity, this immunity wanes over time after a few weeks or months and calves must build their own immunities.
Thomas disclose that earlier vaccinations are becoming a norm in the industry to give calves an edge in the early stages of their lives and Thomas et al suggest that this is carried out when the levels of maternal immunity is not high enough to protect the calf.
Thomas also disclose that giving calves vaccinations at two to three months of age has benefits about the time maternal antibody protection begins to weaken and the response to vaccination depends on how much maternal immunity is received at birth which can interfere with the response to the vaccine.
Based on the teachings of Thomas, the timing of vaccination depends on levels of maternal immunity passed on to calf. Thus, additionally administering the composition at birth; minutes after birth within about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 45, 50, 55 minutes; within about 1-7 days after birth or about 1-8 weeks after birth would have been prima facie obvious as of the effective filing date of the instant invention. The timing could have been determined as a matter of routine optimization based on the levels of maternal immunity in the calf at time of birth as suggested by Thomas.
Status of Claims
Claims 1-2, 4, 9, 24-26, 28 and 42 are rejected. Claims 71-72, 78 and 84-86 are withdrawn.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLUWATOSIN A OGUNBIYI whose telephone number is (571)272-9939. The examiner can normally be reached IFP.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Nickol can be reached on 5712720835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645