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 .
Claims 44-63 are pending with claims 44-57 withdrawn and claims 58-63 examined on the merits.
Election/Restrictions – Maintained In-Part; Non-Responsive, In Part
Applicant’s election without traverse of Group III, claims 58-63, in the reply filed on 9/24/25 is acknowledged:
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However, applicant has not elected any species from each of the 3 required elements of Group III, as required; e.g. applicant did identify as elected, as required, i.e. residues 433-511 of peptide SEQ ID NO: 2; AND residues 19-84 of peptide SEQ ID NO: 140; AND the structure/sequence of a specific immune-response eliciting domain:
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As such, and until these elections are made, a reasonable search of the intended claim scope by election is not presently possible. The examiner has continued onward in the examination on the merits to advance prosecution and in response hereto, applicant may address the rejections below and make the required species elections above, and the examiner will search and examine such and if found allowable, move on to the next species for support/written description is present.
Prior Art Made of Record But Not (Yet) Relied Upon
Zhang et al. (U.S. Patent No. 11,365,239, 6/21/22 Issued, 3/20/20 EEFD):
Anti-SARS-CoV-2 Antibodies and Uses Thereof
The examiner makes reference to the following forty (40) citations within the specification that provide backdrop to the claimed invention but which would need to be submitted in an Information Disclosure Statement (IDS) to have considered on the record (see specification pages 58-61). The examiner makes particular note of the following reference from the list as exemplary of the search for binding affinity by spike proteins of SARS-CoV-2, as applicant sought here: Yi et al. Key residues of the receptor binding motif in the spike protein of SARS- CoV-2 that interact with ACE2 and neutralizing antibodies. Cellular & Molecular Immunology 17:621—630 (2020).
REFERENCES
1. Chi et al. Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain. Nat Commun 11(1):4528 (2020)
2. Choy etal. Synthetic peptide studies on the Severe Acute Respiratory Syndrome (SARS) coronavirus spike glycoprotein: Perspective for SARS vaccine development. Clinical Chemistry 50(6):1036—1042 (2004)
3. Bertoni et al. Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Scientific Reports 7:10480 (2017)
4. Epelman et al. Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights into the endogenous counter-regulatory pathway of the renin- angiotensin-aldosterone system. J Am Coll Cardiol 52(9):750-754 (2008)
5. Ferretti et al. COV/D-19 patients form memory CD8+ T cells that recognize a small set of shared immunodominant epitopes in SARS-CoV-2. Immunity 53(5):P1095- 1107 (2020)
6. Hisatake et al. Serum angiotensin-converting enzyme 2 concentration and angiotensin-(1—7) concentration in patients with acute heart failure patients requiring emergency hospitalization. Heart and Vessels 32(3):303-308 (2017)
7. Hoffmann et al. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell 78(4):779-784 (2020)
8. Krissinel E and Henrick K. Interference of macromolecular assemblies from crystalline state. J Mol Biol 372(3):774—797 (2007)
9. Mansbach et al. The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State. bioRxiv (preprint) 2020.07.26.219741 (2020)
10. Nguyen et al. Human leukocyte antigen susceptibility map for Severe Acute Respiratory Syndrome coronavirus 2. J Virol 94(13):e00510-20 (2020)
11.Ogawa et al. The D614G mutation in the SARS-CoV2 Spike protein increases infectivity in an ACE2 receptor dependent manner. bioRxiv (preprint) 2020.07.21.214932 (2020)
12.Poh et al. Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralizing antibodies in COVID-19 patients. Nature Commun 11:2806 (2020)
13.Remmert et al. HHbiits: lightning-fast iterative protein sequence searching by HMM- HMM alignment. Nature Methods 9:173-175 (2012)
14. Soro-Paavonen et al. Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications. J Hypertens 30(2):375-383 (2012)
15. Studer et al. QWUEANDisCo—distance constraints applied on model quality estimation. Bioinformatics 36(6):1765—1771 (2020)
16. Townend & Tavassoli. 7raceless production of cyclic peptide libraries in E. coli. ACS Chemical Biology 11:1624—1630 (2016)
17.Walls et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181(2):281-292 (2020)
18.Wang et al. /dentification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein. Blood 104(1):200—206 (2004)
19. Wang et al. Accurate de novo prediction of protein contact map by ultra-deep learning mode/. PLoS Computational Biology 13(1):e1005324 (2017)
20.Wang et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 323(18):1843-1844 (2020)
21.Waterhouse et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucl Acids Res 46:W296—W/303 (2018)
22.Wrapp et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:1260—1263 (2020)
23. Zhang et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv (preprint) 2020.06.12.148726 (2020)
24.Zheng & Song. Novel antibody epitopes dominate the antigenicity of spike glycoprotein in SARS-CoV-2 compared to SARS-CoV. Cell Mol Immunol 17:538— 538 (2020)
25. Ou et al. Emergence of RBD mutations in circulating SARS-CoV-2 strains enhancing the structural stability and human ACE2 receptor affinity of the spike protein (2020)
26.Nami et al. The effect of ACE2 inhibitor MLN-4760 on the interaction of SARS-CoV- 2 spike protein with human ACE2: a molecular dynamics study (2020)
27.Chour et al. Shared antigen-specific CD8+ T cell Responses against the SARS- CoV-2 spike protein in HLA-A*02:01 COVID-19 participants. medRxiv preprint 2020.05.04.20085779 (2020)
28. Gutierrez et al. Deciphering the TCR repertoire to solve the COVID-19 mystery. Trends in Pharmacological Science 41(8) (2020)
29. Tseng et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS ONE 7(4):e35421 (2012)
30. Tang et al. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. Tne Journal of Immunology 186(12):7264-7268 (2011)
31.Zhang et al. The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-!. bioRxiv preprint 2020.05.24.111823 (2020)
32. Diao et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Frontiers in Immunology 11(827) (2020)
33. Zheng et al. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cellular &
molecular immunology 17(5):541-543 (2020)
34. Kumar et al. An in-silico based clinical insight on the effect of noticeable CD4 conserved residues of SARS-CoV-2 on the CD4-MHC-II interactions. bioRxiv preprint 2020.06.19.161802 (2020)
35. Woodruff et al. Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation. medRxiv preprint 2020.04.29.20083717 (2020)
36. Woodruff et al. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nature Immunol 21:1506—1516 (2020)
37.Kellam & Barclay. The dynamics of humoral immune responses following SARS- CoV-2 infection and the potential for reinfection. Journal of General Virology 101:791-797 (2020)
38. Seow et al. Longitudinal evaluation and decline of antibody responses in SARS- CoV-2 infection. medRxiv preprint 2020.07.09.20148429 (2020)
39. Robbiani et al. Convergent antibody responses to SARS-CoV-2 infection in convalescent individuals. Nature 584(7821):437—442 (2020)
40. Yi et al. Key residues of the receptor binding motif in the spike protein of SARS- CoV-2 that interact with ACE2 and neutralizing antibodies. Cellular & Molecular Immunology 17:621—630 (2020).
Claim Rejections - 35 USC § 112(a)(i)/(pre-AIA ) – Written Description
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.
Claims 58-63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing/identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, applicant has claimed the following:
ANY ‘truncated peptide fragment’ from the binding interface of SARS-CoV-2 and ACE receptors, respectively, as well as any ‘immune-response eleciting domain:
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However, the examiner only finds limited support for the latter (for which a species election is awaiting still) and as for the 1st two classes of compounds, only finds limited support as well (for which a species election is awaiting still):
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and
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As such, the genus comprising the structural cooperation of each of the elements above cannot be found in possession as to:
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Applicant may consider amending the claims as to each element as to that supported and in possession at the time of filing, which would overcome the 35 USC 112(a)(b) rejections.
See MPEP 2172.01 Unclaimed Essential Subject Matter
This section pertains to guidance for determining whether to make a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, as failing to claim the subject matter that the inventor or a joint inventor (or, for applications subject to pre-AIA 35 U.S.C. 112, the applicant) regards as his or her invention.
Depending on the specific facts at issue, a claim which omits subject matter disclosed to be essential to the invention as described in the specification or in other statements of record may be rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as not enabling (see, e.g., In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976)); under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as lacking an adequate written description (see, e.g., Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473, 45 USPQ2d 1498 (Fed. Cir. 1998)); under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, as indefinite (see, e.g., In re Venezia, 530 F.2d 956, 189 USPQ 149 (CCPA 1976)); or under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, as failing to claim the subject matter that the inventor or a joint inventor (or, for applications subject to pre-AIA 35 U.S.C. 112, the applicant) regards as the invention (see, e.g., In re Collier, 397 F.2d 1003, 158 USPQ 266 (CCPA 1968)). Such essential matter may include missing elements, steps or necessary structural cooperative relationships of elements described by the applicant(s) as necessary to practice the invention.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111; clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry,whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
With the exception of the above, the skilled artisan cannot envision the detailed chemical structure of the encompassed variants, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovinesequence.
Therefore, the full breadth of the claims are not presently deemed to have been in Applicant’s ‘possession’ and found to meet the written description provision of 35 U.S.C. §112.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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 58-63 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.
Claims 58-63 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are the 3 elements below.
To provide evidence satisfying the metes and bounds of the invention here, applicant needs to address the claim the elements in possession and how they fit together/bind in order to make the whole:
ANY ‘truncated peptide fragment’ from the binding interface of SARS-CoV-2 and ACE receptors, respectively, as well as any ‘immune-response eleciting domain:
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However, the examiner only finds limited support for the latter (for which a species election is awaiting still) and as for the 1st two classes of compounds, only finds limited support as well (for which a species election is awaiting still):
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and
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As such, the genus comprising the structural cooperation of each of the elements above cannot be found in possession as to:
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Applicant may consider amending the claims as to each element as to that supported and in possession at the time of filing, which would overcome the 35 USC 112(a)(b) rejections.
See MPEP 2172.01 Unclaimed Essential Subject Matter
This section pertains to guidance for determining whether to make a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, as failing to claim the subject matter that the inventor or a joint inventor (or, for applications subject to pre-AIA 35 U.S.C. 112, the applicant) regards as his or her invention.
Depending on the specific facts at issue, a claim which omits subject matter disclosed to be essential to the invention as described in the specification or in other statements of record may be rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as not enabling (see, e.g., In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976)); under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as lacking an adequate written description (see, e.g., Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473, 45 USPQ2d 1498 (Fed. Cir. 1998)); under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, as indefinite (see, e.g., In re Venezia, 530 F.2d 956, 189 USPQ 149 (CCPA 1976)); or under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, as failing to claim the subject matter that the inventor or a joint inventor (or, for applications subject to pre-AIA 35 U.S.C. 112, the applicant) regards as the invention (see, e.g., In re Collier, 397 F.2d 1003, 158 USPQ 266 (CCPA 1968)). Such essential matter may include missing elements, steps or necessary structural cooperative relationships of elements described by the applicant(s) as necessary to practice the invention.
Claim Rejections - 35 U.S.C. § 112a(ii) – Scope of Enablement (Prevention) – SARS-CoV-2
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.
Claim 61 is rejected under 35 U.S.C. 112, first paragraph, because the specification does not 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 first paragraph of 35 U.S.C. 112 states, “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...”. The courts have interpreted this to mean that the specification must enable one skilled in the art to make and use the invention without undue experimentation. The courts have further interpreted undue experimentation as requiring “ingenuity beyond that to be expected of one of ordinary skill in the art” (Fields v. Conover, 170 USPQ 276 (CCPA 1971)) or requiring an extended period of experimentation in the absence of sufficient direction or guidance (In re Colianni, 195 USPQ 150 (CCPA 1977)). Additionally, the courts have determined that “... where a statement is, on its face, contrary to generally accepted scientific principles”, a rejection for failure to teach how to make and/or use is proper (In re Marzocchi, 169 USPQ 367 (CCPA 1971). Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Colianni, 195 USPQ 150, 153 (CCPA 1977), have been clarified by the Board of Patent Appeals and Interferences in Ex parte Forman, 230 USPQ 546 (BPAI 1986), and are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed Cir. 1988). Among the factors are the nature of the invention, the state of the prior art, the predictability or lack thereof in the art, the amount of direction or guidance present, the presence or absence of working examples, the breadth of the claims, and the quantity of experimentation needed.
Applicants have reasonably demonstrated/disclosed and enabled that one or more products treating SARS-CoV-2 infection. However, the claims also encompass using the same to prevent; which until shown by test data (e.g. vaccine level capacity for the claimed peptide) is clearly beyond the scope of the instantly disclosed/claimed invention. Thus, the instant disclosure fails to meet the enablement requirement for the latter, for the following reasons:
The term "prevent" is interpreted (absent evidence to the contrary) as an absolute definition which means to stop from occurring and, thus, requires a higher standard for enablement than does the term "treat", especially since it is notoriously well accepted in the medical art that the vast majority of afflictions/disorders suffered by mankind cannot be totally prevented with current therapies (other than certain vaccination regimes) – including preventing SARS-CoV-2 infection with the claimed peptide active agents, as presently claimed (which clearly is not recognized in the medical art as being a totally preventable condition).
Accordingly, it would take undue experimentation without a reasonable expectation of success for one of skill in the art to make and/or use the claimed composition, which would function to prevent that claimed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/MAURY A AUDET/Primary Examiner, Art Unit 1654