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
Acknowledgement is hereby made of receipt and entry of the communication filed on Apr. 24, 2024. Claims 1-3, 5-7, 13-16, 18-22, 24-28, 31-33, 35, 37-44, 48-51, and 53-56 are pending and currently examined.
Claim Objections
Claims 2 and 7 are objected to because of the following informalities:
1) Claims 2 and 7 recite “The polypeptide of claim 1(i)” and “The polypeptide of claim 1(ii)”, respectively, which do not comply with formal wording for claim dependency. Applicant may consider such wording like “The polypeptide of claim 1, wherein the……”.
2) Claim 7 recites the description for CDR sequences of SEQ ID NO: 11 twice. It appears that the second description is a typo for CDR sequences of SEQ ID NO: 12.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) (Written Description)
The following is a quotation of the first paragraph 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 1-3, 5, 7, 13, 15-16, 18-22, 24-28, 31-33, 35, 37, 39-44, 48-51, and 53-56 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.
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 had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. See MPEP 2163. I.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material "requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiefs, 984 F.2d at 1171, 25 USPQ2d at 1606). In AbbVie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Court of Appeals, Federal Circuit 2014), the Court ruled that “[W]ith the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim' s functional boundaries.”).”
These claims encompass a polypeptide that specifically binds the S2 subunit of a SARS-CoV-2 spike protein, comprising: (i) the complementarity determining region 1 (CDR1) and CDR3 sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 or SEQ ID NO: 6; or (ii) the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11or SEQ ID NO: 12. The claims are generic to any single polypeptide with only (i) CDR1 and CDR3 sequences of any one of SEQ ID NOs: 1-6, or (ii) CDR1, CDR2, and CDR3 sequences of any one of SEQ ID NOs: 7-12, without specifying the exact sequences of the CDRs.
The Specification teaches the development of single-domain monoclonal antibodies ("nanobodies") that specifically bind the S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The single-domain antibodies were isolated from shark variable domain of new antigen receptor (V NAR) and camel variant domain of heavy chain only antibody (VHH) phage display libraries panned against the S2 subunit of SARS-CoV-2 spike protein. See Abstract.
The instant Specification discloses 12 single-domain antibodies that specifically bind to the SARS-CoV-2 S2, i.e., shark nanobody NCI CoV-S2A9 (S2A9), NCI-CoV-S2G8 (S2G8), NCI-CoVS3A10 (S3A10), NCI-CoV-S4A9 (S4A9), NCI-CoV-S4C12 (S4C12) and NCI-CoV-S6E1(S6E1), and camel nanobody NCI-CoV-CLA2 (CLA2), NCI-CoV-CG2G2 (CG2G2), NCI-CoV-CGH3 (CGH3), NCI-CoV-CGF10 (CGF10), NCI-CoV-CG2D11 (CG2D11) and NCI-CoV-CL3H4 (CL3H4). See [0006]. Each of the single-domain antibodies comprises a specific amino acid sequence (one of SEQ ID NOs: 1-12) and a specific set of CDRs. See [0145]-[0161] and Tables 1-7.
The Specification teaches that a "single-domain antibody" (or “nanobodies”) refers to an antibody having a single domain (a variable domain) that is capable of specifically binding an antigen, or an epitope of an antigen, in the absence of an additional antibody domain. Single-domain antibodies include, for example, V H domain antibodies, V NAR antibodies, camelid V HH antibodies, and V L domain antibodies. V NAR antibodies are produced by cartilaginous fish, such as nurse sharks, wobbegong sharks, spiny dogfish and bamboo sharks. Shark V NAR are comprised of the following regions (N-terminal to C-terminal): FR1-CDR1-FR2-HV2-FR3a-HV 4-FR3b-CDR3-FR4. The positions of CDRl and CDR3 of V NAR antibodies can be determined, for example, using IMGT. HV2 and HV 4 can be determined, for example, using annotation described in Stanfield et al. (Science 305:1770-1773, 2004) and Fennell et al. (J Mal Biol 400:155-170, 2010). Camelid V HH antibodies are produced by several species including camel, llama, alpaca, dromedary, and guanaco, which produce heavy chain antibodies that are naturally devoid of light chains. Camel V HH are comprised of the following regions (N-terminal to C-terminal): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. Camel VHH CDR residues can be determined, for example, according to IMGT, Kabat or Paratome. See [0076].
Juma (Cells 2021, 10, 1140; submitted in IDS filed on Apr. 24, 2024) review of the structure and functional characteristics of antibodies from Shark species (IgNAR). It teaches that different shark species produce different VNARs (variable domains of IgNARs). Variable domains of sharks are formed by four hypervariable loops: CDR1 and CDR3, somatic mutations result in the deletion of CDR2, this position of CDR2 replaced by very short strand referred to as HV2. The HV4 is sited between HV2 and CDR3, this HV4 is believed to contribute to antigen binding. See page 3, para 2.
Teachings of the instant Specification and Juma indicate that the CDRs alone, as specified in the claims, are not sufficient in the formation of a “polypeptide” with the specific antigen-binding activities of the shark or camel single-domain antibodies, instead, the framework and HV regions are also required.
Here, the Specification only discloses 12 single-domain antibodies, 6 of shark origin (SEQ ID NOs: 1-6) and 6 of Camel origin (SEQ ID NOs: 7-12), which comprise respective CDRs that confer the specific antigen-binding activities of the single-domain antibodies when located properly in the sequences containing respective framework and HV regions. Neither the instant Specification or knowledge in the art has evidence that any “polypeptide” comprising the claimed CDRs are sufficient in specific binding of the antigen as claimed. In other words, framework and HV domains of the respective shark and camel antibody sequences are required.
Claims 5 and 13 specify a “polypeptide” of claim 1 with at least 90% sequence identity to one of SEQ ID NOs: 1-12. Since the claim 1 specifies the CDRs, the up to 10% variation must occur in the framework and/or HV domains. As indicated above, the Specification discloses 12 single-domain antibodies from the shark or camel origin, there is guidance as to how the up to 10% of the amino acid sequences of the SEQ ID NOs: 1-12 can be changed without affecting the antigen-binding activity of the antibodies.
Claims 15-16 specify that the polypeptide of claim 1 is a single-domain monoclonal antibody. However, these claims do not specify the structure features of the single-domain monoclonal antibody. Therefore, the single-domain monoclonal antibody is generic which may or may not be represented by the shark (SEQ ID NOs: 1-6) and the camel (SEQ ID NOs: 7-12) single-domain monoclonal antibodies disclosed in the instant application.
Accordingly, the specification does not provide written description support that the Applicant is in possession of the invention in the generic form as claimed.
Allowable Subject Matter
Shark single-domain antibodies comprising amino acid sequence of one of SEQ ID Nos: 1-6 and camel single-domain antibodies comprising amino acid sequence of one of SEQ ID Nos: 7-12 are free of prior art.
Conclusion
No claims are allowed.
Claims 6, 14 and 38 are objected to for depending from a rejection claim.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. 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). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
Prosecution Insights