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
Status of the Claims
1. Claims 1-31 are the original claims filed 3/8/2023. In the Preliminary Amendment of 6/27/2023, claims 1, 15 and 19-20 are amended and claims 21-31 are canceled. In the second Preliminary Amendment of 7/25/2023, the claims are a resubmission of the claim set filed on 6/27/2023. In the Response of 4/16/2026, Claims 1, 9, 15, 19 and 20 are amended and Claims 2-3, 7-8, 10, and 21-31 are canceled.
Claims 1, 4-6, 9, and 11-20 are all the claims.
Applicants’ amendment of the claims raises new grounds for rejection. The Office Action is final.
Priority
2. USAN 18/119,183, filed 03/08/2023, is a Continuation of PCT/US2021/049724, filed 09/09/2021, PCT/US2021/049724 Claims Priority from Provisional Application 63/076,885, filed 09/10/2020.
Information Disclosure Statement
3. As of 5/7/2026, a total of three (3) IDS are filed for this application: 6/27/2023; 12/11/2024; and 8/20/2025. The initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Drawings
4. The objection to the drawing sheets filed on 3/8/2023 for Figure 1 are withdrawn. The replacement drawing sheets of 4/16/2026 are amended to include the sequence identifiers for those sequences > 4 amino acids in length.
Specification
5. The disclosure is objected to because of the following informalities:
a) The specification is amended to rectify the improper use of the term GloMax, BioFX, PURExpress, BiTE, nanobody, DART, Megalign, DNASTAR, which is a trade name or a mark used in commerce.
b) The specification is amended to identify the proper number for amended Figure 1.i.e, from Figure 1A-1VVVV.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 15 and 19-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claim 15 is amended to delete the broad recitation “a single domain antibody”.
b) Claim 15 is amended to delete the broad recitation “camelized antibody”.
c) Claims 19-20 is amended to delete the term “about.”
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
7. The rejection of Claims
Applicants allege “the amended claims comply with the written description requirement. The amended claims contain subject matter which was described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the claimed invention.”
Response to Arguments
Applicants have not explained how the amendments to the claims overcome the rejection, therefore the reply is non-responsive.
Applicant’s specification fully discloses anti-SARS-CoV-2 RBD VHH antibody clones selected to bind the SARS-CoV-2 RBD protein (Sino Biological, Cat. No. 40592-V02H) with the VHH domains disclosed in Figure 1 and Sequence Appendix in the specification. The RBD sequence based on the product data sheet (see PTO 892 form) from Sino Biological comprises “a DNA sequence encoding the SARS-CoV-2 (2019-nCoV) Spike Protein (RBD) (YP_009724390.1) (Arg319-Phe541) expressed with the Fc region of human IgG1 at the C-terminus”. The cloned VHH domains are presumed to be specific for the RBS protein YP_009724390.1 but the region sequence is not specified in the claims.
Applicants amended 1, 4-6, 9, 11-18 to delete “specific” binding for the VHH clones yet the VHH clones in claims 19-20 are required to possess specific binding for the RBD. Accordingly, the distinction between the claimed subject matter is not only unclear but not substantiated by the record data as between specific and non-specific binding.
Inasmuch as the specification teaches a specific DNA sequence for the RBD protein used to generate the VHH clones, Applicants did not respond to the cited art references establishing the art-recognized variation in the RBD protein amongst SARS-CoV-2 isolates:
“The art recognizes protein variation in the RBD region of SARS-CoV-2 where the RBD escape mutations confer resistance of antibody binding and neutralization (Mittal et al (PLoS Pathog 18(2): e1010260; February 17, 2022; See Figure 5 SARS-CoV-2 RBD mutations that escape antibody binding; Safari et al (Archives of Virology (2022) 167:293–305; see Figure 2 Effects of defining genome sequence variations of SARSCoV-2 variants of concern (VOCs) on the domains of the spike protein. A).”
The POSA could reasonably conclude that applicants are not in possession of the myriad anti- SARS-CoV-2 RBD binding VHH domains without sufficient information defining the epitope or the antigen to which the antibodies with “specific” binding or binding (e.g., non-specifically, cross-reactive, etc.)). Applicants have not shown/demonstrated with intrinsic or extrinsic evidence that the VHH antibodies bind to just any variant of a SARS-CoV-2 RBD protein known-or-yet to be discovered (see MPEP II(A)(3)(a)(i)).
The rejection is maintained.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. The rejection of Claim(s) 1-300B (VIB VZW; US 20230227537) or US/18559915 (VIB VZW; US 20240228596) is moot for the canceled claims and maintained for the pending claims.
Applicants allege that in amending claim 1 to recite a negative proviso for the VHH clone comprising the VHH CDR1-3 of SEQ ID NOS: 227-38-45 citing [0153] in the as-filed specification, the amendment overcomes the rejection.
Response to Arguments
A search of both [0153] in the as-filed specification and [0154] in the corresponding PGPub US 20240059759 shows NO per se explicit or implicit contemplation of a negative proviso as instant claimed. A more detailed analysis under 112, 1st paragraph (written description) for new grounds for rejection is set forth below. Accordingly, where no support is found in the specification (or the amended claims) under Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1344, 1351 (Fed. Cir. 2012)), In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977)) or Inphi Corporation v. Netlist, Inc., 805 F.3d 1350, 1356-57, 116 USPQ2d 2006, 2010-11 (Fed. Cir. 2015)), the rejection is maintained.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
9. Claims 1, 4-6, 9, and 11-20 are 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.
a) Claims 1, 4-6, 9, and 11-20 are indefinite where applicants amended claims 1, 4-6, 9, and 11-18 to delete “specific” binding for the VHH clones yet the VHH clones in claims 19-20 are required to possess specific binding for the RBD. Accordingly, the distinction between the claimed subject matter is not only unclear but not substantiated by the record data as between specific binding and binding.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
10. Claims 1, 4-6, 9, and 11-20 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 4-6, 9, and 11-20 are drawn to a negative proviso for the VHH clone comprising the VHH CDR1-3 of SEQ ID NOS: 227-38-45.
Support is present where the specification expressly states the negative limitation (e.g., “the composition may omit compound A”). Support can also be shown if the specification describes a reason to exclude the relevant element, including where such reason is provided in the background section (Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1344, 1351 (Fed. Cir. 2012)). Support for a negative limitation can also be shown if the specification describes alternative elements. That is, if alternative elements are positively recited in the specification, they may be explicitly excluded in the claims (In re Johnson), 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977)). For example, if the specification states that a cation component can include sodium, potassium, calcium, and/or magnesium, a claim specifically excluding sodium would be supported. When using this approach to show support, the applicant is not required to articulate advantages or disadvantages of each feature in order to later exclude the alternative feature (Inphi Corporation v. Netlist, Inc., 805 F.3d 1350, 1356-57, 116 USPQ2d 2006, 2010-11 (Fed. Cir. 2015)).
A) Support is NOT present as here in the present case because the specification does not expressly state the negative limitation.
B) Support is NOT present as here in the present case because the specification does not describe a reason(s) to exclude the relevant element, including where such reason is provided in the background section ((Santarus, Inc.).
C) Support is NOT present as here in the present case because the claimed invention is drawn to myriad combinations of VHCDR1-VHCDR2-VHCDR3 domains that bind any RBD protein known-and-yet to be discovered. Applicants have yet to establish on the record that every possible combination of claimed CDR1-3 regions yields a productive VHH that binds any RBD. Inasmuch as the specification teaches in the Sequence Appendix and Figure 1 the expressed combined pairing that impliedly provides support under for a negative proviso under Inphi, the Office does not have the search capacity to evaluate every VHCDR1-CDR2-CDR3 combination as instantly claimed to identify those that correspond to functional VHH disclosed in the specification.
Conclusion
11. No claims are allowed.
12. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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