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 .
Election/Restrictions
Applicant’s election of Group 1 (drawn to a pharmaceutical composition, claims 1, 6, 10-11) in the reply filed on 4 Mar 2026 is acknowledged. 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)).
Upon further consideration, the restriction requirement between Groups 1 (a pharmaceutical composition, claims 1, 6, 10-11) and 3 (a transgenic attenuated B. mellitensis strain, claims 37-39), as set forth in the Office action mailed on 5 Jan 2026 , has been reconsidered. The restriction requirement between these two groups is hereby withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 12, 14-22, 28, and 30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4 Mar 2026.
Claim Status
The amended claim set filed 4 Mar 2026 is acknowledged. Claims 1, 6, 10-12, 14-22, 28, 30-31, and 37-39 are currently pending. Of those, no claims are currently amended, and no claims are new. Claims 12, 14-22, 28, and 30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4 Mar 2026. Claims 2-5, 7-9, 13, 23-27, and 32-36 are cancelled. Claims 1, 6, 10-11, and 37-39 will be examined on the merits herein.
References to the specification in this action refer to paragraph numbers from US20240374701A1, in order to avoid confusion if future amendments to the specification change the page and line numbers of the cited text.
Inventorship Note
Applicant may wish to confirm that the inventors names are correct as present on the filing receipt. Specifically, a search of the art identified work authored by Paul De Figueiredo and Jianxun Song (see 102 rejection below) and Thomas Ficht, which differs from the spelling on the filing receipt mailed 6 Aug 2024 (copied below). No changes are required if the filing receipt is accurate.
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Priority
The application claims priority to provisional application 63/226,489 (filed 28 July 2021) and is a 371 of PCT/US2022/074252 (filed 28 July 2022). The effective filing date for claims 1, 6, 10-11, and 37-39 is 28 July 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 26 Jan 2024 and 12 Aug 2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. Signed copies of these statements are attached with this action.
Drawings
The drawings are objected to because:
37 C.F.R. 1.84 requires that “India ink, or its equivalent that secures solid black lines, must be used for drawings”, but the text of the figures is pixelated rather than printed in solid lines (see Examiner’s view of Figure 9E below).
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Examiner’s view of Figure 9E (partial figure).
In Figures 1, 2A, 4C, and 9F, the black-and-white images cannot be interpreted because the color spectrum used gets darker at both high and low values.
In Figure 9C, the legend cannot be interpreted because the colors (if present) and shapes (if present) that differentiate the lines are not visible.
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Examiner’s view of Figure 9C (partial figure).
In Figures 1, 7A, 7C, 7F, 8B, 9A-B, 9E, the text is pixelated to the point that it cannot be read (see Examiner’s view of Figure 9E above).
As the drawings appear to have been originally created using colors, it is noted that color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 102
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 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, 6, 10-11 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by de Figueiredo et al. (May 2021; hereafter de Figueiredo; made of record in IDS filed 26 Jan 2024). This reference may be eligible for a 102(b)(1)(A) exception if the author Robert Christopher Alaniz is the same person as the inventor Robert Alaniz, and if the disclosure of the claimed subject matter was made by the shared inventor/author Robert Alaniz only.
De Figueiredo teaches “we engineered an attenuated brucellosis vaccine (Brucella melitensis ΔvjbR Tna) to produce indole”, and that the indole-producing live attenuated bacteria were administered to a collagen induced arthritis (CIA) murine model (Abstract). For claim 37, the claimed tryptophanase “tnaA” is presumed to be the same as the disclosed “Tna”, absent evidence to the contrary, due to the very similar name and same function of producing indole.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by APPLICANT ADMITTED ART.
The instant specification states at [0017]: “the live attenuated bacterial strain of Brucella melitensis is Brucella melitensis 16M ΔvjbR (BmΔvjbR). … Methods of making and obtaining BmΔvjbR have been previously described, for instance in Arenas-Gamboa et al., Clin Vaccine Immunol, 2012; 19:249-60, de Figueiredo et al., Am J Pathol, 2015; 185:1505-17, Pandey et al., Methods Mol Biol, 2014; 1197:229-44, and Pandey et al., Front Cell Infect Microbiol, 2018; 8:103…”. See MPEP 2129: “Where the specification identifies work done by another as "prior art," the subject matter so identified is treated as admitted prior art. In re Nomiya, 509 F.2d 566, 571, 184 USPQ 607, 611 (CCPA 1975)”. The preamble “a pharmaceutical composition” does not differentiate the claim from the admitted art because there is no evidence of record that a composition comprising the bacteria alone, which are admitted to have been previously described, is not suitable for use as a pharmaceutical composition. Neither the claim nor the specification defines any structures that must be present in the composition beyond the bacterial strain itself.
Claims 1 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ficht et al. (US-20140248354-A1; hereafter Ficht; PTO-892).
Regarding claim 1, Ficht teaches the B. melitensis 16M ΔvjbR strain, and teaches that mice inoculated with the strain “do not show any clinical or major pathologic changes associated with vaccination” [0033], so the strain is attenuated. Ficht teaches compositions comprising the bacteria [0010]. Regarding claim 6, Ficht teaches that the compositions can optionally comprise an adjuvant (i.e. a second therapeutic agent) [0010]. Ficht also teaches composition can comprise other therapeutic and prophylactic agents [0060].
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 6, 10-11 and 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over de Figueiredo et al. (May 2021; hereafter de Figueiredo; PTO-892) in view of Mani et al. (US-20150258151-A1; hereafter Mani; PTO-892).
De Figueiredo teaches “we engineered an attenuated brucellosis vaccine (Brucella melitensis ΔvjbR Tna) to produce indole”, and that the indole-producing live attenuated bacteria were administered to a collagen induced arthritis (CIA) murine model (Abstract). For claim 37, the claimed tryptophanase “tnaA” is presumed to be the same as the disclosed “Tna”, absent evidence to the contrary, due to the very similar name and same function of producing indole.
De Figueiredo does not teach that the tnaA is expressed under the control of a constitutive promoter, as in claim 38, and does not teach that the tryptophanase (tnaA) comprises E. coli tnaA, as in claim 39.
Mani teaches bacteria that produce an indole [Abstract]. Mani teaches “In an embodiment, the bacterium is a recombinant bacterium genetically engineered to constitutively-express an indole-producing enzyme. … In a preferred embodiment, the tryptophanase is an E. Coli tryptophanase.” [0031].
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to improve the De Figueiredo indole-producing bacteria by choosing promoters and genes that are preferred for making indole producing bacteria as taught in Mani, thereby arriving at the claimed invention, because de Figueiredo is silent on the methodological details that would be needed to replicate their work, and Mani teaches the details that were preferred by one of ordinary skill in the art at the time of filing. Therefore the combination would be desirable because using art-recognized promoters and genes may make it easier to produce a disclosed indole-producing bacteria. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.”
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the prior art (de Figueiredo) teaches a product that only differs from the claimed invention by the substitution of a single component (i.e. choice of the promoter or gene used based on the generic disclosure, for claims 38-39, respectively); the substituted element (i.e. the constitutive promoter and E. coli tnaA) was already known and already shown to function as a promoter/gene that can be used in an indole-producing bacteria, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of substituting one promoter/gene for another with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
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 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US 9248176 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, ‘176 claim 1 teaches a “vaccine [(i.e. pharmaceutical)] composition comprising: a Brucella melitensis comprising one or more attenuating gene knockouts”. Regarding claim 6, ‘176 claim 2 teaches “the composition further comprises an adjuvant” (i.e. a second therapeutic agent).
Claims 1 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US 10220084 B2, either alone or in view of Ficht et al. (US-20140248354-A1; hereafter Ficht; PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, ‘084 claim 1 teaches a “vaccine [(i.e. pharmaceutical)] composition comprising: a Brucella strain comprising one or more attenuating gene knockouts selected from at least one of ΔvjbR…” and ‘084 claim 2 teaches the Brucella can be Brucella melitensis. Claim 1 is anticipated by ‘084 alone.
The claims of ‘084 are silent on the presence of a second therapeutic agent, as in claim 6.
Regarding claim 1, Ficht teaches the B. melitensis 16M ΔvjbR strain, and teaches that mice inoculated with the strain “do not show any clinical or major pathologic changes associated with vaccination” [0033], so the strain is attenuated. Ficht teaches compositions comprising the bacteria [0010]. Regarding claim 6, Ficht teaches that the compositions can optionally comprise an adjuvant (i.e. a second therapeutic agent) [0010]. Ficht also teaches composition can comprise other therapeutic and prophylactic agents [0060].
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to improve the attenuated Brucella vaccine of the claims of ‘084 by adding an adjuvant as taught by Ficht, thereby arriving at the claimed invention, because Ficht specifically teaches that an adjuvant can be added to the same attenuated Brucella vaccine/pharmaceutical composition. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case all elements (i.e. the attenuated Brucella from the claims of ‘084, the adjuvant for an attenuated Brucella vaccine of Fisch) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the invention of claim 6 is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US 10940193 B2, either alone or in view of Ficht et al. (US-20140248354-A1; hereafter Ficht; PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, ‘193 claim 1 teaches a “method of making a vaccine [(i.e. a pharmaceutical composition)] against brucellosis in an animal subject comprising the steps of: providing a double mutant strain of Brucella comprising one or more attenuating gene knockouts…”, and ‘193 claim 2 teaches the Brucella can be Brucella melitensis. Claim 1 is anticipated by ‘193 alone.
As in ‘084 above, the claims of ‘193 are silent on the presence of a second therapeutic agent, as in claim 6. The teachings of Ficht and the rationale for combining are the same as disclosed above. The invention of claim 6 is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US 11975060 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, ‘060 claim 1 teaches a vaccine (i.e. pharmaceutical) composition comprising: “a double mutant Brucella strain comprising one or more attenuating gene knockouts…” ‘060 claim 2 teaches the Brucella can be Brucella melitensis. Regarding claim 6, ‘176 claim 1 teaches the vaccine comprises an adjuvant (i.e. a second therapeutic agent).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA N DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-F 8:30-4:30 (EDT/EST).
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, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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