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
1. Applicant’s amendment and response filed 6/5/26 is acknowledged and has been entered. Applicant’s said amendment omitting disclosure of the general formula for the CDRs at Table 1 and [0033]-[0060] of the specification does not constitute new matter since it does not alter the scope of the claimed invention as the CDRs recited in the claimed invention are presently fully defined (see MPEP 608.04(a)).
2. Applicant is reminded of Applicant's election with traverse of Group I, claim 1, drawn to a VVH1 targeting IL-23A comprising framework regions and complementary determining regions; the framework regions comprise VVH1 FR-H 1-4 corresponding to SEQ ID NO: 4-7 and the CDRs comprise VVH1 CDRH 1-3 corresponding to SEQ ID NO: 1-3 in Applicant’s amendment and response filed 1/21/26.
Claim 1 reads upon elected Group I. Accordingly, claims 2-4 (non-elected Group II) remain withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Please note that the instant application is not a 371 filing and these said withdrawn product claims will not be rejoined in the event the elected product becomes allowable.
Claim 1 is presently being examined.
3. Applicant is reminded that acknowledgment is made of Applicant's claim for foreign priority based on an application filed in China on 11/06/2024 (i.e., China 202411575470.0). It is noted, however, that applicant has not filed a certified copy of the China 202411575470.0 application as required by 37 CFR 1.55.
4. Applicant’s amendment filed 6/5/26 has overcome the prior rejection of record of claim 1 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.
Applicant has amended the claim to recite that the CDRs and the FRs consist of the sequences corresponding to the recited SEQ ID NOs and has recited the name of a specific antibody “VHH1”.
5. Applicant’s amendment filed 6/5/26 has overcome the prior rejection of record of claim 1 under U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
Applicant has amended the claim to recite that the CDRs and the FRs consist of the sequences corresponding to the recited SEQ ID NOs and has recited the name of a specific antibody “VHH1”.
6. Applicant’s amendment filed 6/5/26 has overcome the prior rejection of record of claim 1 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.
Applicant has deleted the recitation of the trademark NANOBODY.
7. 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.
8. Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not disclose how to use the instant invention, a single domain VHH1 antibody targeting IL-23A, wherein the single domain targeting IL-23A
comprises framework regions and complementary determining regions (CDRs), the framework regions (FR) consisting of amino acid sequences corresponding to SEQ ID NO: 4 (FR-H1), SEQ ID NO: 5 (FR-H2), SEQ ID NO: 6 (FR-H3), and SEQ ID NO: 7 (FR-H4), and the CDRs consisting of the amino acid sequences corresponding to SEQ ID NO: 1 (CDR-H1), SEQ ID NO: 2 (CDR-H2) and SEQ ID NO: 3 (CDR-H3). In their proper order FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 the components correspond to SEQ ID NO: 4-1-5-2-6-3-7, respectively.
The state of the art is such that it is unpredictable in the absence of appropriate evidence whether the claimed VHH can be used for its recited purpose in targeting IL-23A. The specification has not enabled the breadth of the claimed invention because the claims encompass a single domain antibody termed “VHH1” that targets (i.e., binds to) IL-23A but has extra sequence either in the CDR-H1 (LRLSCATSAFIFRLNT, SEQ ID NO: 1) or the FR-H1 (EVQLVESGGGLVQAFFSLRLSCATS, SEQ ID NO: 4) relative to that found in the “VHH1” antibody sequence (SEQ ID NO: 8). The redundant sequence is underlined in both the FR-H1 and the CDR-H1. It is therefore unpredictable that the claimed single domain VHH1 antibody comprising the recited component portions can bind to IL-23A and be used for its recited purpose of targeting IL-23A. A comparison of a search of the concatenated FR and CDR sequences in their proper order (i.e., SEQ ID NO: 4-1-5…………-2-6-3-7) with the sequence of SEQ ID NO: 8 (i.e., the sequence of the “VHH1” antibody) is shown below.
“Qy” is the concatenated sequence of the FR and CDRs in order, whereas the “Db” corresponds to SEQ ID NO: 8 the sequence of the “VHH1” antibody. The redundant sequence is underlined and bolded.
Qy 1 EVQLVESGGGLVQAGGSLRLSCATSLRLSCATSAFIFRLNTMGWYRQAPGKQRELVAMVT 60
Db 1 EVQLVESGGGLVQAGG SLRLSCATSAFIFRLNTMGWYRQAPGKQRELVAMVT 52
Qy 61 IDGSTNYADSVKGRFTISRDSTKNTMYLQMNSLKPEDTAVYYCKADRRIMMRTYDYWGPG 120
Db 53 IDGSTNYADSVKGRFTISRDSTKNTMYLQMNSLKPEDTAVYYCKADRRIMMRTYDYWGPG 112
Qy 121 TQVTVSSEPKTPKPQP 136
Db 113 TQVTVSSEPKTPKPQP 128
The specification discloses the framework and CDR sequences at Table 1 of the specification as well as the sequence of the “VHH1” single domain antibody. This said single domain antibody consists of in order: SEQ ID NO: 4, 1, 5, 2, 6, 3 and 7 (i.e., FR-H1, CDR-H1, FR-H2, CDR-H2, FR-H3, CDR-H3, FR-H4) (see last entry in Table 1 that corresponds to SEQ ID NO: 8).
Evidentiary reference Jovcevska and Muyldermans (BioDrugs, 2020, 34: 11-26, of record) teaches that VHHs or ‘nanobodies' (single domain antibodies) have the same structural architecture as VH domains of human immunoglobulins: four conserved sequence regions (framework regions FR 1/2/3/4) are surrounding three hypervariable antigen binding loops or complementarity determining regions CDRs 1/2/3. Although CDR3 is the main contributor for antigen recognition and specificity, while CDR1 and CDR2 assist in the binding strength, the three CDRs and also regularly, framework residues are involved in the interaction with the antigen and the CDRs may be different lengths from antibody to antibody (see entire reference, especially section 1.2).
Evidentiary reference Jovcevska and Muyldermans (BioDrugs, 2020, 34: 11-26, of record) teaches that VHHs or ‘nanobodies’ (single domain antibodies) have the same structural architecture as VH domains of human immunoglobulins: four conserved sequence regions (framework regions FR 1/2/3/4) are surrounding three hypervariable antigen binding loops or complementarity determining regions CDRs 1/2/3. Although CDR3 is the main contributor for antigen recognition and specificity, while CDR1 and CDR2 assist in the binding strength, the three CDRs and also regularly, framework residues are involved in the interaction with the antigen (see entire reference, especially section 1.2).
Thus, these said evidentiary references confirm a tenant well known to the skilled artisan for antibodies in general and including for VHHs, namely that the CDRs in their proper order and in the context of proper framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function.
There is insufficient guidance in the specification as to how to use the instant invention, as it is unpredictable that the single domain antibody recited in claim 1 may not be operative. See In re Wands 8 USPQ2d 1400 (CAFC 1988).
Applicant may potentially obviate this rejection by amending the claim to recite that the VHH1 targeting IL-23A comprises the sequence consisting of SEQ ID NO:8.
9. 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.
10. Claim 1 recites the limitation “single-domain VHH1 antibody targeting IL-23A” at line 1 and also “VHH1” with regard to the FR and CDRs recited in the claim, yet it also recites that the VHH1 CDR-H1 consists of the sequence shown as SEQ ID NO: 1 and the VHH1 FR-H1 consists of the sequence shown as SEQ ID NO: 4. There is insufficient antecedent basis for this limitation in the claim because the sequence of the “VHH1” antibody corresponds to SEQ ID NO: 8 (see Table 1 of the specification and the sequence listing), and as is enunciated above in this office action, the concatenation of VHH1 FR-H1 with VHH1 CDR-H1 results in extraneous sequence common to both that is only present once in SEQ ID NO: 8.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, MISOOK YU can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
