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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08 April 2026 has been entered.
Status of the Application
2. The amendments and response filed 08 April 2026 is acknowledged and has been considered in its entirety. Claims 8, 10-12, and 19 are pending and subject to examination on the merits.
Change in Examiner/Locale
3. The location and examiner assigned to the instant Application at the USPTO has changed. Please direct all further correspondence to Art Unit 1656 and to the Examiner signed below.
Priority
4. This application is a CON of 17/320,471 filed 14 May 2021, which is a CON of 16/239,871 filed 04 January 2019 (US Pat. No. 11041217), which claims benefit of 62/614,096 filed 05 January 2018.
Specification
5. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p. 2, lines 20 and 24). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
6. The use of the terms Qiagen QIAprep™ (p. 25, line 27), Qiagen HiSpeed™ (p. 25, line 28), Invitrogen Novex™ (p. 27, line 27), which is 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.
Withdrawn Rejections
7. The previous 35 US.C. 103 rejection of claims 8, 10, 11, and 19 as being unpatentable over Moscoso et al. (Virulence 9(1): 604-620; 11/7/2024 IDS, NPL doc# 2; previously cited), Cabral et al. (Nature Communications 8: 15480 doi: 10.1038/ncomms15480 (2017); 11/7/2024 IDS, NPL doc # 1; previously cited), and Zhang et al. (Molecular Microbiology 49(6): 1577-1593 (2003); 11/7/2024 IDS, NPL doc #6; previously cited) is withdrawn. Said rejection has been withdrawn in view of the new rejection below.
Modified Rejections
Claim Rejections - 35 USC § 112(b)
8. Claims 8, 10-12, and 19 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.
8. Claim 8 is unclear because it refers to a method of making a recombinant Staphylococcus bacterium but then recites an introduction/administration step at the end. Specifically, there are two methods recited in the single claim; i.e. “a method for making a recombinant Staphylococcus…” and “introducing the bacterium…” For increased clarity, it is suggested the claim preamble be amended to recite “A method of making and administering a recombinant…” Claims 10-12 and 19 are included in the instant rejection, since they do not mitigate the issue. For examination purposes the claim will be interpreted as suggested, i.e. drawn to a method for making and administering.
New Claim Rejections
Claim Rejections - 35 USC § 103
9. 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.
10. Claims 8, 10-11, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over German (German et al., 2017, ES 2586979 B1—cited on the IDS dated 07 November 2024; English translation provided herein) and Zhang et al. (Zhang et al., 2003, Molecular Microbiology—cited on the IDS dated 07 November 2024). Regarding claims 8 and 10, drawn to a method of making a recombinant Staphylococcus bacterium with D-alanine auxotrophy for introduction into a human microbiome comprising: (i) transforming a plasmid comprising D-alanine aminotransferase (dat) knockout into competent cells of a Staphylococcus strain, wherein the Staphylococcus strain comprises inactive alanine racemase genes air1 and alr2 (SEΔalr1Aalr2), and wherein the Staphylococcus strain comprises a bacterium from the S. epidermidis group; (ii) detecting the presence of the knockout plasmid in transformed cells; (iii) incubating the transformed cells identified in step (ii); (iv) purifying isolated colonies; (v) testing the isolated colonies for D-alanine auxotrophy with PCR (claim 10); (vi) selecting those bacterium from the isolated colonies with D-alanine auxotrophy; and (vii) introducing the bacterium with D-alanine auxotrophy into a target environment, wherein the target environment is a human microbiome, thereby making a recombinant Staphylococcus bacterium with D-alanine auxotrophy for introduction into a human microbiome, German teaches bacterial strains of S. aureus for D-alanine auxotrophy as vaccines in mammals, sufficiently avirulent, wherein said S. aureus induces acceptable protection against infection by S. aureus in a mammal (abstract). Specifically, the method comprises the inactivation of the alr1 and alr2 genes, encoding the alanine racemase 1 enzyme and the dat gene encoding the O-amino acid transaminase, such that the strain is no longer capable of expressing either protein (p. 2, paragraph 7 to p. 3, paragraph 1). German et al. continues to teach the introduction of a plasmid to knock out the three genes into S. aureus and the subsequent growth and screening of the colonies via growth on TSB agar and subsequent PCR confirmation of gene deletion (p. 4-5, Fig. 4-Fig. 6 descriptions, and Fig. 4-Fig. 6). German et al. continues to teach testing the S. aureus auxotroph mutants in TSB versus TSB supplemented with O-alanine, where said mutants cannot survive without alanine supplementation (p. 5, Fig. 7 description, Fig. 7). Last, German et al. teaches the introduction of the S. aureus mutants to BALB/c mice as a vaccine against a S. aureus infection, where the vaccinated mice (with S. aureus mutants) demonstrated increased survival over unvaccinated mice (Figures 15-16; p. 6 Fig. 15-16 descriptions).
German et al. does not teach S. epidermidis (claims 8, 11, and 19) and the introduction to a human microbiome.
Zhang et al. teaches that S.epidermidis is a facultative anaerobic bacteria, part of the normal human flora and further, that although S. epidermidis is not usually pathogenic, patients with compromised immune systems are at risk of developing infection and these infections are generally hospital-acquired. Zhang et al. also teaches that S. epidermidis is a particular concern for people with catheters or other surgical implants because it is known to form biofilms that grow on these target environmental devices (Introduction).
Therefore, it 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 combine the teachings of German et al. and Zhang et al. to create auxotrophic S. epidermidis to provide protection against nosocomial acquired S. epidermidis infections. One would be motivated to combine these teachings to arrive at the instant claims to develop a vaccine to provide protection against S. epidermidis infections, akin to the vaccine utilizing the same strategy in S. aureus, as taught by German et al. There would be reasonable expectation of success, yielding no surprising results when combining the teachings of German et al. and Zhang et al., since German et al. describes the genetic knockout strategy and subsequent environmental introduction of the closely related S. aureus.
Double Patenting
11. 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.
12. Claims 8, 10-12, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-8, 10, and 12-16 of U.S. Patent No. 11041217. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are drawn to a method of making a recombinant Staphylococcus bacterium with D-alanine auxotrophy for introduction into a human microbiome comprising: (i) transforming a plasmid, specifically pUBTR119*-Sal-GFP (claim 12), comprising D-alanine aminotransferase (dat) knockout into competent cells of a Staphylococcus strain, wherein the Staphylococcus strain comprises inactive alanine racemase genes air1 and alr2 (SEΔalr1Aalr2), and wherein the Staphylococcus strain comprises a bacterium from the S. epidermidis group; (ii) detecting the presence of the knockout plasmid in transformed cells; (iii) incubating the transformed cells identified in step (ii); (iv) purifying isolated colonies; (v) testing the isolated colonies for D-alanine auxotrophy with PCR (claim 10); (vi) selecting those bacterium from the isolated colonies with D-alanine auxotrophy; and (vii) introducing the bacterium with D-alanine auxotrophy into a target environment, wherein the target environment is a human microbiome, thereby making a recombinant Staphylococcus bacterium with D-alanine auxotrophy for introduction into a human microbiome.
The ’217 claims are drawn to a composition and method of making a recombinant Staphylococcus bacterium comprising: (i) transforming a plasmid comprising D-alanine aminotransferase (dat) knockout into competent cells of a Staphylococcus strain, wherein the Staphylococcus strain comprises inactive alanine racemase genes alr1 and alr2 (SEΔalrz1alr2); (ii) detecting the presence of the knockout plasmid in transformed cells; (iii) incubating the transformed cells identified in step (ii); and (iv) purifying isolated colonies; and (v) testing the isolated colonies for D-alanine auxotrophy, wherein the recombinant Staphylococcus bacterium is Staphylococcus epidermidis (S. epidermis), and subspecies thereof.
Thus, the difference between the ‘217 claims and the instant claims is that the instant claims recite an administration step of S. epidermis. Therefore, this is a case of process of making/using and product made/used, which is obvious.
It is well established in the courts, for example, in Geneva Pharms. Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, (Fed. Cir. 2003), and Pfizer v. Teva, 518 F.3d 1353 (Fed Cir. 2008). In Geneva, the earlier patent claimed a compound and the specification disclosed its effectiveness for inhibiting beta-lactamase. The later filed patent claimed a method of using the compound to affect beta-lactamase inhibition. Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation; the later filed patent claimed a method of using these compounds for treating inflammation. In both cases, the court ruled that the claims were not "patentably distinct," and thus the latter claims were invalid for obviousness-type double patenting. In a further decision by the Federal Circuit, the same sort of rationale of looking to the specification to preferred embodiments was reiterated, even in CIP applications for products and methods of making or using said products; see Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010). Also see MPEP 804.01(A).
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
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