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 16 June, 2026. Claims 1-17, 20, 25, 26, 28, 29, 31-34, and 36 are pending in the instant application. Applicants’ election of Group I (claims 1-9) without traverse is noted. Because Applicants 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)). Claims 11-17, 20, 25, 26, 28, 29, 31-34, and 36 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
37 C.F.R. § 1.98
The information disclosure statements filed 10 October, 2023, and 15 October, 2024, have been placed in the application file and the information referred to therein has been considered.
37 C.F.R. § 1.84
The drawings filed 17 May, 2023, have been reviewed and are acceptable.
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 2 and 8 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).
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).
Determination of adequate written description requires the Examiner to read and analyze the specification for compliance with 35 U.S.C. § 112(a). In particular, each claim should be analyzed to determine its broadest reasonable interpretation consistent with written description. Each claim should be evaluated to determine if sufficient structures, acts, or functions are recited to make clear the scope and meaning of the claim, including the weight to be given the preamble. The entire application should be reviewed including the specific embodiments, figures, and sequence listings, to understand how applicant provides support for the various features of the claimed invention. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention. Such a review is conducted from the standpoint of one of ordinary skill in the art at the time the application was filed (see, e.g., Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 865, 26 USPQ2d 1767, 1774 (Fed. Cir. 1993)) and should include a determination of the field of the invention and the level of skill and knowledge in the art. Finally, the Examiner should determine whether there is sufficient written description to inform a skilled artisan that the inventor was in possession of the claimed invention as a whole at the time of filing.
Claims 2 and 8 are directed toward an engineered antigen comprising a modified SARS-CoV-2 RBD sequence comprising SEQ ID NO.: 2, or a substantially identical or conservatively modified variant thereof. The claims encompass a large genus of engineered RBD variants. Substantially identical or conservatively modified variants could encompass single or multiple amino acid substitutions, insertions, or deletions within the RBD. This protein (SEQ ID NO.: 2) contains the following amino acid sequence:
NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL390 CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN450 YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV510 VVLSFELLHA PATVCGP527. It has been well-documented that single or multiple amino acid changes can alter the antigenic properties of the RBD (Li et al., 2020; Guo et al., 2021; Yi et al., 2021; Upadhyay et al., 2021). Li et al. (2020) examined a number of SARS-CoV-2 S mutants and identified several mutants with increased infectivity, decreased sensitivity to neutralizing antisera, and decreased sensitivity to convalescent sera (see Table 1, p. 1291). Guo et al. (2021) generated a series of engineered RBD variants and observed that placement of N-linked glycosylation sites was critical for antigenicity and immunogencity. Yi et al. (2021) examined four antigenic sites in the RBD and noted that single amino acid substitutions could alter ACE2 binding activity and neutralizing antibody responses. Finally, Upadhyay et al. (2021) examined a series of mutants comprising single or multiple substitutions and noted that these mutations altered protein expression, thermal stability, decreased ACE2 binding, and increased neutralization resistance. Accordingly, the skilled artisan cannot reasonably predict how any given amino acid substitution, insertion, or deletion will affect the various properties of the RBD region.
Furthermore, while the disclosure provides a finite number of well-defined RBD mutants as set forth in SEQ ID NOS.: 3, 162-168, and 241-246, nevertheless, the claim language encompasses an inordinate number of RBD mutants. However, the specification fails to disclose the isolation and characterization of a sufficient number of species. Moreover, considering the unpredictability of the prior art, the skilled artisan would not be able to reasonably predict or identify suitable RBD mutations. Clearly Applicants were not in possession of a sufficient number of antigenic species.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that the claims are not fully supported by the specification. Amendment of the claim language to incorporate those species enumerated supra would obviate the rejection.
Scope of Enablement
Claims 1-9 are rejected under 35 U.S.C. § 112(a), because the specification does not reasonably enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The claims are broadly directed toward an engineered SARS-CoV-2 RBD antigen comprising various modifications that introduce N-linked glycosylation sites, as well as, hydrophobic residues into the inter-subunit interface. The specification describes the generation, isolation and characterization of a limited number of RBD variants with the recited characteristics (e.g., SEQ ID NOS.: 3, 162-168, and 241-246). Amendment of the claim language to incorporate these mutants would be acceptable.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965).
The claim breadth encompasses an inordinate number of RBD variants comprising multiple amino acid substitutions, insertions, or deletions. RBD sequences that are substantially identical or conservatively modified variants of the parent sequence are also claimed.
The specification fails to provide adequate guidance pertaining to the generation of RBD variants with the desired properties. This protein (SEQ ID NO.: 2) contains the following amino acid sequence:
NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL390 CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN450 YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV510 VVLSFELLHA PATVCGP527.
However, adequate guidance is not presented with respect to those amino acid substitutions that will produce a glycosylation pattern that enhances RBD variant antigenicity. Inadequate guidance is also provided with respect to those amino acid substitutions that will stabilize the inter-subunit interface.
The state of the art can be characterized by unpredictability. It has been well-documented that single or multiple amino acid changes can alter the antigenic properties of the RBD (Li et al., 2020; Guo et al., 2021; Yi et al., 2021; Upadhyay et al., 2021). Li et al. (2020) examined a number of SARS-CoV-2 S mutants and identified several mutants with increased infectivity, decreased sensitivity to neutralizing antisera, and decreased sensitivity to convalescent sera (see Table 1, p. 1291). Guo et al. (2021) generated a series of engineered RBD variants and observed that placement of N-linked glycosylation sites was critical for antigenicity and immunogencity. Yi et al. (2021) examined four antigenic sites in the RBD and noted that single amino acid substitutions could alter ACE2 binding activity and neutralizing antibody responses. Finally, Upadhyay et al. (2021) examined a series of mutants comprising single or multiple substitutions and noted that these mutations altered protein expression, thermal stability, decreased ACE2 binding, and increased neutralization resistance. Accordingly, the skilled artisan cannot reasonably predict how any given amino acid substitution, insertion, or deletion will affect the various properties of the RBD region.
Finally, the specification provides a limited number of working examples. In particular, RBD variants comprising SEQ ID NOS.: 3, 162-168, and 241-246 had the desired properties. However, no other RBD variants were provided.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that undue experimentation would be required to make and/or use the invention commensurate in scope with these claims.
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 19 September, 2026
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