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
Claim Status
Claims 1-15 are currently pending. Claims 4-5, 7-8, 13, 15 have been amended. There are no new or canceled claims. Claims 1-15 will be examined on the merits.
Priority
Acknowledgement is made of applicant’s claim for foreign priority based on an application filed on June 17, 2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement (IDS)
The IDS submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1-3, 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (US Pat. 11414646 B2; hereafter Kim; PTO-892).
As claim 1-3, 5 Kim teaches “the prophylactic vaccine effect of Rv2299c protein or RV2299c-ESAT6 fused protein on Mtb HN878 clinical isolates. These results suggest that Rv2299c-mature DCs induce Th1 cell responses to anti-tuberculous immune activities, and a fusion protein including Rv2299c and ESAT-6 as a novel concept of the DC-activated protein-based vaccine is a promising vaccine target for boosting BCG. See columns 1-3.
Kim teaches “A composition for inducing maturation of dendritic cells, the composition comprising a fusion protein of Rv2299c and ESAT-6 as an active ingredient”. See claim 1.
Kim teaches “ESAT-6 is selected as a fusion partner because ESAT-6 is one of the major antigens included in the vaccine in current clinical trials. See column 21; lines 23-26.
Kim teaches, SEQ ID NOs: 1 is 100% identical to Rv2299c of M. tuberculosis, and SEQ ID NOs: 1. SEQ ID NOs: 2-5 are within SEQ ID NO: 1. See Table 1; See figure below.
SEQ ID NO: 6 is 100% identical to ESAT-6, which is pertinent to claims 2, 3. See Figure below.
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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.
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.
Claims 4, 6, 9-10, 14 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US Pat. 11414646 B2; hereafter Kim; PTO-892) as applied to claims 1-3, 5 above, in view of Back et al. (Published March 8, 2019; hereafter Back; PTO-892).
Kim teaches the limitations of claims 1-3, 5 in view of Back as fully discussed above and incorporated herein.
However, Kim does not teach the fusion protein has BCG-cell wall skeleton (BCG-CWS) conjugated to a terminus thereof and wherein the tuberculosis vaccine composition is a vaccine for prevention or treatment of tuberculosis as claim 4, 6, 9-10, 14.
Back teaches Mycobacterium bovis bacillus Calmette-Guérin cell-wall skeleton (BCG-CWS) has been used as an effective immune-stimulator, which is pertinent to claims 4, 6, 9-10, 14.
Back teaches the BCG-CWS effectively coupled with Ag85B and enhanced the conjugated Ag85B activity on the maturation of dendritic cells (DCs), which is pertinent to claims 4,6, 9-10, 14.
Back teaches “Ag85B-BCG-CWS-matured DCs induced significant Th1 and Th17 responses when compared to BCG-CWS or Ag85B alone. In addition, significant Ag85B-specific Th1 and Th17 responses were induced in Ag85B-BCG-CWS-immunized mice before infection with M. tuberculosis and maintained after infection. Moreover, Ag85B-BCG-CWS showed significant protective effect comparable to live BCG at 6 weeks after infection and maintained its protective efficacy at 32 weeks post-challenge, whereas live BCG did not. The BCG-CWS may be an effective adjuvant candidate for a protein-based vaccine against tuberculosis (TB)”, which is pertinent to claims 4, 6, 9-10, 14.
Back teaches that BCG-CWS plays an essential role to induce both the Th1 and Th17 responses to the conjugated antigen, which is pertinent to claims 4, 6, 9-10, 14.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Kim and Back by using the Rv2299c-ESAT-6 fused protein having BCG-cell wall skeleton (BCG-CWS) conjugated to a terminus thereof to be used as a tuberculosis vaccine composition, thereby arriving at the invention of claims 4, 6, 9-10, 14. Since the Rv2299c-ESAT-6 fused protein of Kim and the BCG-cell wall skeleton (BCG-CWS) conjugated to a BCG antigen were both shown to be effective in generating an immune response against Mycobacterium tuberculosis, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
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.
Claims 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US Pat. 11414646 B2; hereafter Kim; PTO-892) as applied to claims 1-3, 5 above, in view of Back et al. (Published March 8, 2019; hereafter Back; PTO-892) and further view of Xin et al. (Published March 15, 2013; hereafter Back; PTO-892).
Kim teaches the limitations of claims 1-3, 5 in view of Back as fully discussed above and incorporated herein.
However, neither Kim nor Back teach--- the fusion protein further comprises, at a terminus thereof, at least one M. tuberculosis-derived antigen selected from the group consisting of RpfE, Rv3463, Rv2005c, Rv2882c, Rv2145c, Rv1605, Rv2220, and Rv0869c or an immune-active domain thereof.
Xin teaches subunit vaccine consisting of multi-stage antigens has high protective efficacy against Mycobacterium tuberculosis infection in mice, which is pertinent to claim 7.
Xin teaches that antigens expressed in different growth stages of Mycobacterium tuberculosis (M. tuberculosis), such as RpfE (Rv2450c) produced in the stage of resuscitation, Mtb10.4 (Rv0288), Mtb8.4 (Rv1174c), ESAT6 (Rv3875), Ag85B (Rv1886c) mainly secreted by replicating bacilli, and HspX (Rv2031c) highly expressed in dormant bacilli, were selected to construct six fusion proteins: ESAT6-Ag85BMPT64190-198-Mtb8.4 (EAMM), Mtb10.4-HspX (MH), ESAT6-Mtb8.4, Mtb10.4-Ag85B, ESAT6-Ag85B, and ESAT6-RpfE, which is pertinent to claim 7. See for example figure 7.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Kim and Back by adding another M. tuberculosis antigen, such as RpfE to the Rv2299c-ESAT-6 fused protein of Kim and the BCG-cell wall skeleton (BCG-CWS) conjugated to a terminus thereof of Black, thereby arriving at the invention of claim 7. Since the Rv2299c-ESAT-6 fused protein of Kim and the BCG-cell wall skeleton (BCG-CWS) conjugated to a BCG antigen were both shown to be effective in generating an immune response against Mycobacterium tuberculosis, and the ESAT6-RpfE fused protein of Xin also was shown to be used as a vaccinal antigen candidate against M. tuberculosis, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
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.
Claims 8, 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US Pat. 11414646 B2; hereafter Kim; PTO-892) as applied to claims 1-3, 5 above, in view of Back et al. (Published March 8, 2019; hereafter Back; PTO-892) and further view of Spencer et al. (WO 2011045612 A1; hereafter Spencer; PTO-892).
Choi teaches the limitations of claims 1-3, 5 in view of Back as fully discussed above and incorporated herein.
However, neither Kim nor Back teach the fusion protein further comprises, at a terminus thereof, at least one M. tuberculosis-derived antigen or an immune-active domain thereof as claim 8.
Kim and Back do not teach the tuberculosis vaccine composition is a vaccine for prevention or treatment of tuberculosis. as claim 12.
Spencer teaches polynucleotides and fusion proteins, to vectors, to immunogenic compositions and to methods and uses thereof for the treatment or prevention of mycobacterial infections, particularly in primates such as man, mycobacterial vaccines, which is pertinent to claims 8, 12. See for example, Abstract and Description.
Spencer teaches the second domain comprises a mycobacterial antigen selected from 85A/Rv3804c, 85B/Rv1886c, 85C/Rv0129c, ESAT6/Rv3875, TB10.4/Rv0288, Rv0125, PPE18/Rv1 196, P27/Rv141 1 c, HSP65/Rv0440, HBHA/Rv0475, Rv2659c, Rv2660c, HspX/Rv2031 c, RPFA/Rv0867c, RPFB/Rv1009, RPFC/Rv1884c, RPFD/Rv2389c, RPFE/Rv2450c, Rv1733c, Rv2029c, Rv2032, Rv2626c, Rv2627c, Rv2628, Rv01 1 1 , Rv1806/1807, Rv0198, or Rv3812 or antigenic fragments thereof, which is pertinent to claims 8, 12. See for example, claims 3, 19.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Kim and Back by adding another M. tuberculosis antigen, such as RpfED1 to the Rv2299c-ESAT-6 fused protein of Kim and the BCG-cell wall skeleton (BCG-CWS) conjugated to a terminus thereof of Black, thereby arriving at the invention of claims 8, 12. Since the Rv2299c-ESAT-6 fused protein of Kim and the BCG-cell wall skeleton (BCG-CWS) conjugated to a BCG antigen were both shown to be effective in generating an immune response against Mycobacterium tuberculosis, and Spencer teaches mycobacterial antigens, and antigen fusions to be used in a vaccinal composition, such as ESAT6/Rv3875, RPFD/Rv2389c and RPFE/Rv2450c, it would be advantageous and very desirable to have vaccines containing multiple antigens to induce broader immune responses and provide better protection against M. tuberculosis, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
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.
Claims 13, 15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US Pat. 11414646 B2; hereafter Kim; PTO-892) as applied to claims 1-3, 5 above, in view of Back et al. (Published March 8, 2019; hereafter Back; PTO-892) and further view of Choi et al. (Published March 31, 2018; hereafter Choi; PTO-892) as evidenced by Park et al. (Published March 12, 2019; hereafter Park, PTO-892)
Kim teaches the limitations of claims 1-3, 5 in view of Back as fully discussed above and incorporated herein.
However, neither Kim nor Back teach the fusion protein further comprises, at a terminus thereof, at least one M. tuberculosis-derived antigen or an immune-active domain thereof as claim 13.
Kim and Back do not teach the tuberculosis vaccine composition is a vaccine for prevention or treatment of tuberculosis. as claim 15.
Choi teaches that the M. tuberculosis protein Rv2220 induces maturation and activation of dendritic cells, which is pertinent to claims 13, 15.
Choi teaches that “Specifically, Rv2220-matured dendritic cells (DCs) induced the expansion of memory CD62LlowCD44highCD4+ T cells in the spleen of mycobacteria-infected mice. Choi2 teaches that Rv2220 regulates host immune responses through maturation of DCs, a finding that points to a new vaccine candidate against tuberculosis”, which is persistent to claims 13, 15.
Choi teaches that splenocytes from mycobacteria-infected mice manifested increased production of IFN-γ and IL-2 under the influence of Rv2220-matured DCs as compared to ESAT-6-matured DCs, which is pertinent to claims 13, 15. See for example, Figure 4C.
Choi teaches that Rv2220-specific IFN-γ and IL-2 production were observed in the lung cells from Rv2220-immunized mice, which is pertinent to claims 13, 15. See for example, Supplementary Figure 1.
Park teaches Rv3463, a newly identified hypothetical protein, activated macrophages to induce mycobactericidal activity that was strongly associated with rise in phospatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and an intracellular Ca2+, which is pertinent to claims 13, 15.
Park teaches M. tuberculosis Rv3463 induces mycobactericidal activity in macrophages by enhancing phagolysosomal fusion and exhibits therapeutic potential, which is pertinent to claims 13, 15.
Rv3463 expression in M. smegmatis caused rapid clearance in macrophages and mice. Moreover, Rv3463 exhibited therapeutic potential in a Mtb-infected mouse model, which is pertinent to claims 13, 15.
Park teaches Park teaches that Rv3463 is a promising target for the development of post-exposure tuberculosis vaccines or adjunct immune-therapy, which is pertinent to claims 13, 15.
Park teaches that “Although candidate TB vaccines have focused on T-cell stimulating antigens, proteins that induce the bactericidal activity in macrophages can be ideal vaccine targets, particularly for the development of a post-infectious vaccine”, which is pertinent to claims 13, 15.
Park teaches that ESAT-6, which has promising potential as a post-exposure vaccination, was used as a control antigen. The mycobacterial burdens in the lungs and spleens were determined at 2 weeks after the final immunization. Rv3463- and ESAT-6-immunized groups had significantly reduced bacterial loads in the lungsRv3463 showed a significantly higher therapeutic efficacy than ESAT-6, which is pertinent to claims 13, 15.
Park teaches that Rv2882c protein induce macrophage activation and exhibit potential for use as a vaccine such as the BCG booster, which is pertinent to claims 13, 15.
SEQ ID NOs: 23, 6, 19 were searched. *SEQ ID NO: 23 is 100% identical (Rv2220) to SEQ ID NO: 156 of US Pat. 8486414. See Figure below. *SEQ ID NO: 6 is 100% identical (ESAT-6) to SEQ ID NO: 294 of US Pat. 8486414. See Figure below. See also *Reed et al. (US Pat. 8486414; PTO-892).
SEQ ID NO: 19 is 100% identical to a putative F420-dpendent oxidoreductase from M. tuberculosis. See Figure below. SEQ ID NO: 19 is Rv3463 as taught by claims 8, 13.
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It would have been obvious to one of ordinary skill in the art to combine the teachings of Choi1 and Back by replacing Rv2299c (or its immune-active domain) by other promising vaccinal candidate M. tuberculosis antigens, such as Rv2220 and Rv3463 to the ESAT-6 fused protein construction of Choi1 and the vaccinal adjuvant (BCG-cell wall skeleton (BCG-CWS)) conjugated to a terminus thereof, of Black, thereby arriving at the invention of claims 13, 15. Since the Rv2299c-ESAT-6 fused protein of Choi1 and the BCG-cell wall skeleton (BCG-CWS) conjugated to a BCG antigen were both shown to be effective in generating an immune response against Mycobacterium tuberculosis, and both Choi2 and Park teach promising mycobacterial vaccinal antigens, and compare their activity to ESAT-6, which is also a promising vaccinal antigen, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
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 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., vaccinal and/or therapeutical antigens of Mycobacterium sp., vaccinal adjuvants, such as the BCG-CWS, vaccines containing multiple antigens to induce broader immune responses and provide better protection against M. tuberculosis, designing of chimeric antigens/epitopes, including the use of linkers) 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 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 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 10-11 of Kim et al. (U.S. Patent No. 1414646 B2; hereafter Kim; PTO-892).
646’ discloses “A composition for inducing maturation of dendritic cells, the composition comprising a fusion protein of Rv2299c and ESAT-6 as an active ingredient”. See 646’, claim 1.
642’ discloses “the Rv2299c is a protein derived from M. tuberculosis”. See 646’, claim 2.
642’ discloses “a composition for enhancing immunity of claim 1, claim 2”. See 646’, claims 10-11.
Although the claims at issue are not identical, they are not patentably distinct from each other because Rv2299c and ESAT6 fusion proteins are the same of U.S. Patent No. 1414646 B2, or protein domains/sequences of these fusion protein are within the SEQ ID NO: 1 and ESAT-6 protein of U.S. Patent No. 1414646 B2.
Therefore, claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 10-11.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571) 272-2784. The examiner can normally be reached 6:15AM-3:15PM.
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/PRICILA NMN HAUK TEODORO/ Examiner, Art Unit 1645
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684
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