Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 29 December, 2025. Claims 1-14 are pending in the instant application. Applicant’s elected Group I (claims 1-12) for examination on the merits. 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 (M.P.E.P. § 818.03(a)). Accordingly, claims 13 and 14 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
35 U.S.C. § 119
Acknowledgment is hereby made of Applicant’s claim for foreign priority pursuant to 35 U.S.C. § 119(b) and 37 C.F.R. § 1.55 based on CL 2568-2020, filed 05 October, 2020. A certified copy of this application was received. However, an English translation did not accompany this document. In order to be perfect the foreign priority claim, an English translation of this application is required pursuant to 35 U.S.C. § 119(b)(3) and 37 C.F.R. § 1.55(g)(3). Accordingly, the foreign priority claim has NOT been entered at this time.
37 C.F.R. § 1.84
The drawings filed 04 April, 2023, have been reviewed and are acceptable.
37 C.F.R. § 1.98
The information disclosure statement filed 04 April, 2023, has been placed in the application file and the information referred to therein has been considered.
35 U.S.C. § 112(b)
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.
Claims 1-12 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
Claim 1 references an immunogenic formulation comprising an attenuated recombinant Mycobacterium Bacillus Calmette-Guérin (BCG) “in an amount om a range from 104 to 109 CFU per dose.” This limitation is confusing and the precise metes and bounds of the patent protection desired cannot be readily ascertained. Appropriate correction is required.
35 U.S.C. § 112(a)
The following is a quotation of 35 U.S.C. § 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Written Description
Claims 3, 4, 6, and 7 are rejected under 35 U.S.C. § 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. Amgen, Inc. v. Sanofi, 872 F.3d 1367, 124 U.S.P.Q.2d 1354 (Fed. Cir. 2017). AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 111 U.S.P.Q.2d 1780 (Fed. Cir. 2014). Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920, 69 U.S.P.Q.2d 1886, (Fed. Cir. 2004). Enzo Biochem, Inc. v. Gen-Probe, Inc., 296 F.3d 1316, 63 U.S.P.Q.2d 1609, (Fed. Cir. 2002). Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 U.S.P.Q.2d 1398, (Fed. Cir. 1997). Fiers v. Revel Co., 984 F.2d 1164, 25 U.S.P.Q.2d 1601, (Fed. Cir. 1993). Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016, (Fed. Cir. 1991). In re Rasmussen, 650 F.2d 1212, 211 U.S.P.Q. 323 (C.C.P.A. 1981). In re Wertheim, 541 F.2d 257, 191 U.S.P.Q. 90 (C.C.P.A. 1976).
As previously set forth, the crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. In re Kaslow, 707 F.2d 1366, 1375, 217 U.S.P.Q. 1089, 1096 (Fed. Cir. 1983). In re Wilder, 736 F.2d 1516, 1520 222 U.S.P.Q. 349, 372 (Fed. Cir. 1984, cert. denied, 469 U.S. 1209 (1985). Texas Instruments, Inc. v. International Trade Comm’n, 871 F.2d 1054, 1063, 10 U.S.P.Q.2d 1257, 1263 (Fed. Cir. 1989). Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. In re Wertheim, 541 F.2d 257, 263, 191 U.S.P.Q. 90, 97 (C.C.P.A. 1976). In re Driscoll, 562 F.2d 1245, 1250, 195 U.S.P.Q. 434, 438 (C.C.P.A. 1977). It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations. Martin v. Mayer, 823 F2d 500, 505, 3 U.S.P.Q.2d 1333, 1337 (Fed. Cir. 1987).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
The claims are directed toward immunogenic formulations comprising a recombinant Mycobacterium BCG encoding an Andesvirus protein. In particular, proteins comprising at least 75% amino acid sequence identity to the N protein of SEQ ID NO.: 1, or the nucleotide sequence encoding said N protein (SEQ ID NO.: 2) are contemplated. The Andes hantavirus N protein is 428 amino acids in length and contains the following amino acid sequence:
MSTLQELQEN ITAHEQQLVT ARQKLKDAEK AVEVDPDDVN KSTLQNRRAA VSTLETKLGE LKRQLADLVA AQKLATKPVD PTGLEPDDHL KEKSSLRYGN VLDVNSIDLE EPSGQTADWK AIGAYILGFA IPIILKALYM LSTRGRQAVK DNKGTRIRFK DDSSFEEVNG IRKPKHLYVS MPTAQSTMKA EEITPGRFRT IACGLFPAQV KARNIISPVM GVIGFGFFVK DWMDRIEEFL AAECPFLPKP KVASEAFMST NKMYFLNRQR QVNESKVQDI IDLIDHAETE SATLFTEIAT PHSVWVFACA PDRCPPTALY VAGVPELGAF FSILQDMRNT IMASKSVGTA EEKLKKKSAF YQSYLRRTQS MGIQLDQKII ILYMLSWGKE AVNHFHLGDD MDPELRQLAQ SLIDTKVKEI SNQEPLKL (SEQ ID NO.: 1; 428 aa).
The claims encompass a large genus of polypeptide and nucleotide variants. For example, 25% amino acid sequence variation of the Andesvirus N protein produces upwards of ~7 x 10227 variant sequences.1 Even a little as 5% amino acid sequence variation produces an inordinate number of protein variants (~6 x 1064).
However, the specification fails to identify the preparation and characterization of any additional N protein variants. The specification fails to identify which molecular determinants of the N protein are sine qua non for generating protective or therapeutic immune responses. There is no discuss about which portions of the N protein can tolerate amino acid insertions, deletions, or substitutions while retaining immunogenicity. Moreover, it has been well-documented that single amino acid changes can alter the antigenicity and immunogenicity of a protein.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicants were not in possession of a sufficient number of species to support the full breadth of the patent protection desired.
Joint Inventors, Common Ownership Presumed
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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed 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.
35 U.S.C. § 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 of this title, 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.
Claims 1-12 are rejected under 35 U.S.C. § 103 as being unpatentable over Bueno Ramierez et al. (U.S. Pat. No. 9,999,663 B2, issued 19 June, 2018; hereinafter referred to as “Bueno Ramierez et al. (2018)”), in view of Petsch and Jasny (WO 2019/038332 A1, published 28 February, 2019; hereinafter referred to as “Petsch and Jasny (2019)”). The claims are directed toward an immunogenic formulation conferring protection against Hantavirus and/or the development of Hantavirus cardiopulmonary syndrome (HCPS), comprising: an attenuated recombinant strain of Mycobacterium Bacillus Calmette-Guerin (BCG), in an amount between 104 to 109 CFU per dose, which expresses at least one protein or immunogenic fragment of virus Andesvirus (ANDV), in a pharmaceutically acceptable saline buffer solution. Claim 2 is directed toward an immunogenic formulation according wherein the at least one protein or immunogenic fragment of the Andesvirus corresponds to the N protein or immunogenic fragments thereof. Claims 3 and 4 are directed toward an N protein corresponding to SEQ ID NO.: 1. Claim 5 specifies the nature of the insert. Claims 6 and 7 reference nucleotide sequences encoding the N antigen of SEQ ID NO.: 1. Claims 8 and 9 are directed toward the utilization of different promoters and expression strategies. Claims 10 and 11 reference freeze-dried preparations of the immunogenic formulation. Claim 12 recites a recombinant BCG Danish or Pasteur vector.
Bueno Ramierez et al. (2018) describe the preparation of immunogenic formulations comprising recombinant Mycobacterium Bacillus Calmette-Guérin encoding for human Metapenumovirus (hMPV) immunogens (see Fig. 1). Suitable dosages and formulations were clearly described (see DETAILED DESCRIPTION OF THE INVENTION, cols. 7-10). Detailed methods of preparation were also provided (see Example I, Generation of a Recombinant Vector Allowing the Expression of the hMPV P-protein in Mycobacterium BCG, cols. 10-11; Example II, Immunogenic Formulation Comprising 10 Doses of 1x108 CFU Each of BCG Danish Strain Recombinant for the P Gene from hMPV Subtype, cols. 11-12). This teaching meets all of the claimed limitations except for the expression of a hantavirus antigen.
Petsch and Jasny (2019) provide mRNA vaccines for the treatment of buynavirus, and other, viral infections. In particular this teaching provides both nucleotide and amino acid sequences encoding the Andesvirus N protein (see SEQ ID NOS.: 2571 and 236, respectively).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the recombinant BCG vaccine vector system of Bueno Ramierez et al. (2018), to incorporate the Andesvirus N protein of Petsch and Jasny (2019), to produce robust immune responses against hantaviruses. One of ordinary skill in the art would have been particularly motivated to utilize the recombinant BCG system of Bueno Ramierez et al. (2018) because it provides strong immune responses using limited sample sizes.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 04 April, 2026
1 These calculations were performed as follows: TV=(NY)(X!)/(Y!)((X-Y-1)!), wherein, TV=the total number of variant sequences, N=the number of amino acids or nucleotides that can be substituted (i.e., if any of the 20 naturally occurring amino acids can be substituted, N=19; if any of the four naturally occurring nucleotides can be substituted, N=3), Y=the number of amino acids/nucleotides in the parent sequence that can be substituted (i.e., if the amino acid sequence is 100 aa in length and 10% genetic variation is allowed, Y=10 [100@10%]), and X=the total sequence length of the sequence of interest.
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