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 .
DETAILED ACTION
1. Applicant’s preliminary amendment filed on January 30, 2024 is acknowledged. Claims 3-5, 8, 12-13, 15-18, 23, and 25-26 have been amended. Claims 6-7, 19-22, and 24 have been canceled. Claims 1-5, 8-18, 23, and 25-27 are currently pending.
Election/Restriction
2. REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claim(s) 1-5, 8, 9, 23 and 25, drawn to a vaccine against Clostridium chauvoei.
Group II, claim(s) 10-18, drawn to a method of preparing a vaccine against C. chauvoei infection.
Group III, claim(s) 26-27, drawn to a method of preventing C. chauvoei infection.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Group I-III lack unity of invention because even though the inventions of these groups require the technical feature of a vaccine comprising C. chauvoei and a cctA protein, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Zaragoza et al., Toxins, 2019; 11(525): 1-29. Zaragoza et al., discloses the vaccine production comprising C. chauvoei and CctA (see pages 1-13; C. chauvoei vaccine production).
During a telephone conversation with Vyacheslav Vasilyev on December 15, 2025 a provisional election was made without traverse to prosecute the invention of Group II, claims 10-18. Affirmation of this election must be made by applicant in replying to this Office action. Claims 1-5, 8, 9, 23, and 25-27 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 10-18 are currently under examination.
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on May 2, 2024 and January 28, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. An initialed copy is attached hereto.
Specification
4. The use of multiple terms found within paragraph 0045, which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
5. The disclosure is objected to because of the following informalities: throughout the specification are instances of ‘C chauvoei’ it should be ‘C. chauvoei’.
Appropriate correction is required.
Claim Objections
6. Claims 10, 12 and 17-18 are objected to because of the following informalities: on first site ‘C chauvoei’ should be ‘Clostridium chauvoei’. Additionally, any place that recites ‘C chauvoei’ should actually recite ‘C. chauvoei’. Appropriate correction is required.
7. Claims 11, 14 and 18 are objected to because of the following informalities: the limitation, for example, ‘The method of claim 13’ there should be a comma following each number. Appropriate correction is required.
8. Claims 11 and 13-16 are objected to because of the following informalities: said claims are dependent upon a rejected based claim. Appropriate correction is required.
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 (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.
9. Claim 17 and 18 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.
Said claim is rendered vague and indefinite by the use of the term “component”. It is unclear what is meant by said term, as it is not explicitly defined in the specification. What constitutes a “C. chauvoei component”? What core features/structures must be maintained? As written, it is impossible to determine the metes and bounds of the claimed invention.
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.
Claim Rejections - 35 USC § 103
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.
10. Claim(s) 10, 12 and 18 are rejected under 35 U.S.C. 102((a)(1)) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Zaragoza et al., Toxins, 2019; 11(525):1-29, and further in view of the following references, which are relied upon in Zaragoza; Cortinas et al., Journal of Applied Bacteriology, 1994, 77: 382-387 (reference #201); and Frey et al., Vaccine, 2012; 30:5500-5505 (reference #193).
Independent claim 10 is drawn to a method of preparing a vaccine against C. chauvoei infection, said method comprising: a) culturing C. chauvoei; b) collecting culture media; c) concentrating C. chauvoei from said culture media; d) concentrating cctA from said culture media; and e) combining said concentrated cctA with C. chauvoei.
Zaragoza teaches that C. chauvoei bacterin vaccines consist of whole formalin-inactivated bacterial cultures, which are expected to have all the components believed to be involved in blackleg pathogenesis. Zaragoza teaches that the production of the vaccine is a straightforward process consisting of growing C. chauvoei in fermenters for 24 h at 37 °C. Cultures are then formalized for approximately six days at 37 °C to inactivate the cells [201]. The complex medium contains casein hydrolysate, peptone, tryptone, yeast extract, and meat extract, plus L-cysteine hydrochloride, glucose, and salts [201](see page 12; vaccine production; meets claims 10 and 12)[201: Cortinas]. Additionally, animals vaccinated with recombinant CctA developed high immunity against C. chauvoei challenges, making this toxin a valuable candidate for the design of a toxoid vaccine against blackleg [193: Frey] (meetings claim 10 and 18).
Cortinas et al. disclose that for vaccine production it is desirable that high cellular density cultures with high immunogenic power are obtained, mainly because immunity to CI. chauvoei is generally considered to be antibacterial rather than antitoxic. Consequently, culture conditions have to be adequately monitored and controlled. In order to optimize the process it is also convenient to examine changes in the cultures in terms of various growth parameters. Clostridium chauvoei, like other clostridia, produce acids and solvents which can accumulate at elevated levels, preventing the production of high density cell cultures (see introduction).
Cortinas discloses methods of growing Clostridium chauvoei in a clostridia medium containing (g 1- ') : proteose-peptone, 20; yeast extract, 5 ; MgSO, . 7H,O, 1.5; cysteine chlorhydrate, 0-75; glucose 5; K,HPO. The last two components were sterilized separately and added to the basal medium after sterilization. The medium was modified by the addition of glucose at 10 g 1 - and with glucose partial feeding (see page 382; medium). Clostridium chauvoei was grown anaerobically in batch cultures in a 350 ml fermenter with 250 ml of culture medium. Cultures were incubated at 37°C, unless otherwise indicated, under the following conditions: (1) with free pH evolution, and a glucose concentration of 5 g 1-'; (2) with pH control at glucose concentrations of 5 and 10 g I-'. Cultures were grown at pH 6-5 & 0-1 with an automatic pH controller provided with a solenoid valve for the addition of 3 mol 1-' NaOH. After the exponential growth phase began the cultures were slowly agitated with a magnetic stirrer; (3) with pH control and partial glucose feeding. The pH was fixed at 6.5 _+ 0.1, and glucose was added as 1 ml fractions of a previously sterilized concentrated glucose solution (250 g 1-I). The partial addition of glucose was carried out to keep cultures under glucose-limiting conditions. This was achieved by setting the glucose feeding device to operate only upon total consumption of the carbon source, detected by the interruption of alkali additions necessary to neutralize pH, at each point. The exhaustion of glucose was positively confirmed by an enzymatic test. The effect of temperature was analyzed under condition one at 30, 37, 40 and 44.5"C in static cultures. Cultures were started with a 10% (v/v) inoculum obtained in clostridia medium in the late exponential growth phase. The anaerobic conditions required for growth of Cl. chauvoei were met by the addition of 0.75 g 1-' of cysteine chlorhydrate to clostridia medium, and the inoculation of media immediately after they were sterilized and cooled. It was observed that after growth started no additional measures were necessary (see page 382; growth conditions).
Further, Culture growth was monitored by optical density determinations at 580 nm (O.D. 580) with a Spectronic 20 spectrophotometer. The final biomass concentration was estimated by dry weight determinations. Cells were harvested by centrifugation at 4000 g for 15 min at PC, in an RC-5B automatic refrigerated superspeed centrifuge, washed twice in isotonic salt solution, resuspended in a small volume of double distilled water and finally lyophilized in a Thermovac FD 6 freeze-drier (RES Inc., Island Park, New York, USA) at a vacuum pressure of 300 milliTorr (see page 383; biomass determination).
Moreover, the protein content of CE was determined by the method of Lowry et al. (1951) with bovine serum albumin as protein standard. Butanol was determined on centrifuged and filtered culture samples by gas-liquid chromatography in a 5700 A Hewlett Packard gas chromatograph provided with a 180 x 0.3 cm Carbowax 1640 packed column and a flame ionization detector.
Furthermore, Frey teaches a novel protein toxin, named Clostridium chauvoei toxin A (CctA) that belongs to the family of β-barrel pore forming toxins of the leucocidin superfamily of bacterial toxins was discovered by whole genome sequence analysis. The corresponding gene cctA was found in all strains of C. chauvoei analyzed, isolated from various geographical areas over the globe during the last 50 years, but not in other pathogenic Clostridium species.
The C. chauvoei and Escherichia coli strains used are listed in Table 1. C. chauvoei was grown under standard anaerobic conditions on Tryptic Soy Agar medium containing 5% sheep erythrocytes or in liquid Brain Heart Infusion medium supplemented with 0.05% l-cysteine, at 37 °C. E. coli strains were grown on Luria–Bertani (LB) broth or agar at 37 °C. Plasmids were selected with 100 μg/ml ampicillin (see section 2.1). Supernatants of C. chauvoei cultures were obtained by removing the cells by centrifugation at 10,000 × g for 30 min. Native toxin was purified. Purification of rCctA::NusA was done by nickel chelation chromatography as described [27]. Cleavage of the Nus and His tags from the recombinant protein to obtain mature rCctA was done using the thrombin cleavage capture kit (Novagen) and resulted in a protein with a molecular mass of 32 kDa (see section 2.4).
The teachings of the combination of references anticipates and in the alternative is obvious over the rejected claims.
Conclusion
11. No claim is allowed.
12. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Roberts-WO 94/22476
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAKIA J JACKSON-TONGUE/ Examiner, Art Unit 1645 February 19, 2026
/BRIAN GANGLE/ Primary Examiner, Art Unit 1645