DETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant's election with traverse of Group I claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 in the reply filed on 10/28/2025 is acknowledged. The traversal is on the ground that unity of the invention apply at the national stage and restriction between compositions and methods of their use is an improper ground for lack of unity. This is not found persuasive because the unity of invention is overcome by obviousness of the claimed special feature as recited in the prior office action for Election/Restriction.
Species election: Applicant elected species without traverse as recited in response filed on 10/28/2025.
(i). a VH of SEQ ID NO.: 38, comprising HCDRs of SEQ ID NOs: 34, 35, and 37, and a VL of SEQ ID NO.: 62, comprising LCDRs of SEQ ID NOs: 41, 49, and 55.
Applicant’s election of species (ii) A polynucleotide sequence, (iii) A polymerase inhibitor, and (iv) RNAi agent, reads on claims belonging to Group of inventions (other than elected Group I) that lack with group I inventions and the species therefore are not examined.
The election of Group I claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 and the elected species that read on claims in Group I is made final.
The requirement is still deemed proper and is therefore made FINAL.
Priority
3. This application is 371 of PCT/US2021/038667 filed on 06/23/2021 and claims priority to US provisional application 63/043,692 filed on 06/24/2020.
Information Disclosure Statement
4. The information disclosure statements (IDSs) submitted on 11/13/2023, 01/09/2024, 01/09/2024, 04/15/2024, and 10/28/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
5. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
6. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See, page 24 (www.chemcomp.com).
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
7. The use of the term ExpiCHO (pages 36 and 83), Octet (pages 47), which is a trade name, or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Status of Claims
8. Claims 3, 9 ,13-16, 18, 23, 30-31, 33-54, 60-72, 74, 76, 83, 118, 125, 130, 133, 135, 137, 139, 143, 151-152, 166-167, 170, 174 and 187-193 are pending.
9. Claims 60-72,74,76,83,118,125,130,133,135,137,139,143,151-152,166-167,170,174 and 187-193 are withdrawn from consideration due to restriction.
10. Claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 are under examination in this office action.
Claim Interpretation
11. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
The elected Group I claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 and inventions in this application are directed to an antibody or engineered antibody or antigen-binding fragment thereof that binds HBV S antigen and neutralize HBV, and the antibody is administered or used for treatment of HBV infection in a subject. The antibodies or CDRs comprise engineered variations for broadly reactive binding activity to HBV S antigen or for broadly neutralizing activity against different genotypes of HBV, and also bind or neutralize to HDV for therapeutic applications.
Claim 3: The instant claim 3 is interpreted to comprise different claim limitations and variations, (i) an antibody that is a polyclonal antibody obtained from an HBV vaccinated or infected and recovered patient, (ii) an antibody that is a monoclonal antibody obtained from a mouse immunized with HBV antigen and clonal selection from a hybridoma, (iii) an antibody, a variant antibody that is sequenced and engineered to comprise CDRs with specific amino acid substitution(s), (iv) heavy and light chain antigen-binding fragments (CDRs) derived from the engineered antibody or a natural antibody.
The claim limitation “according to” is interpreted as closed limitation “consisting of” or “in the” that as claimed and recited in the SEQ ID NO.
The limitations after the “wherein” clause is interpreted to be optional and that may or may not be necessary to enable the claim to the claimed narrow scope prior to introducing “wherein” clause in the claim 3. However, to enable the claim broadly the amino acid variations recited as optional limitations after the “wherein” clause is necessary.
Claim 9: The instant claim 9 is interpreted to comprise the variant antibody or antigen-binding fragments comprised in VH (SEQ ID NO: 38) and VL (SEQ ID NO: 62) with the variant species comprising amino acid sequence identity (e.g. 90%, 99%).
Claims 47-54: Based on election of the antibody species, claims 47-54 are interpreted to comprise a VH of SEQ ID NO: 38, comprising HCDRs of SEQ ID NOs: 34, 35, and 37, and a VL of SEQ ID NO: 62, comprising LCDRs of SEQ ID NOs: 41, 49, and 55.
For examination purpose, the elected Group I (elected claims 3, 9, 13-16, 18, 23, 30-31 and 33-54) are interpreted to comprise elected species a VH of SEQ ID NO.: 38, comprising HCDRs of SEQ ID NOs: 34, 35, and 37, and a VL of SEQ ID NO.: 62, comprising LCDRs of SEQ ID NOs: 41, 49, and 55.
The instant elected claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 are interpreted to be directed to comprise an antibody, monoclonal antibody (e.g. monoclonal antibody HBC34 variant(s), recited in the instant specification) in view of the instant specification (page 21 para 2, page 22, para 2) that recites, the term "antibody" refers to an intact antibody is used in the broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments thereof.
Claim Rejections - 35 USC § 112
12. 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.
The claims 3, and dependent claims 9, 13, 15-16, 18, 23, 30-31, and 33-54 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.
The instant claim 3 recite optional limitations that the VL comprises a R60N, a R60A, a R60K, a S64A, a I74A substitution mutation or any combination thereof, relative to SEQ ID NO: 58 and amino acid numbering for the mutation(s) is according to SEQ ID NO: 58 (length is 106 amino acid). The amino acid sequence of the elected VH and VL comprising CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences are according to SEQ ID NOs.: (i) 34, 35, 37, 41, 49, and 55, respectively, are recited separately and the VL or VH CDRs are not linked and therefore the sequences are <60 amino acid and alignment cannot be performed to identify or perform search of the mutation in the database. Applicant is required to recite a VL sequence comprising SEQ ID NO: 41, 49 and 55 in a searchable format to allow perform the amino acid alignment and comparison. In the current format the optional limitations following the wherein clause in claim 3 cannot be examined.
Claim Rejections - 35 USC § 112
13. 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.
The instant claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 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.
The instant claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 require an antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising a CDRH1 amino acid sequence, a CDRH2 amino acid sequence, and a CDRH3 amino acid sequence; and
a light chain variable region (VL) comprising a CDRL1 amino acid sequence, a CDRL2 amino acid sequence, and a CDRL3 amino acid sequence, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences are according to SEQ ID NOs.: (i) 34, 35, 37, 41, 49, and 55, respectively (elected species),
wherein CDRs are defined according to the CCG numbering system,
wherein, optionally, the VL comprises a R60N substitution mutation, a R60A substitution mutation, a R60K substitution mutation, a S64A substitution mutation, a I74A substitution mutation, or any combination thereof, relative to SEQ ID NO.:58 and wherein the amino acid numbering of the substitution mutation(s) is according to SEQ ID NO.:58, and still further optionally wherein the VL does not comprise any further mutation(s) relative to SEQ ID NO.:58, and wherein the antibody or antigen-binding fragment thereof is capable of binding to the antigenic loop region of HBsAg and, optionally, neutralizing infection by a hepatitis B virus (HBV) of genotype D, A, B, C, E, F, G, H, I, or J, or any combination thereof.
The instant specification (page 21 para 2, page 22, para 2) recites, the term "antibody" refers to an intact antibody is used in the broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments thereof, including fragment antigen-binding (Fab) fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single chain antibody fragments, including single chain variable fragments (scFv), and single domain antibodies (e.g., sdAb, sdFv, nanobody) fragments.
The instant claim 9 require the antibody or antigen-binding fragment of claim 3, wherein the VH and the VL comprise or consist of amino acid sequences having at least 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences set forth in SEQ ID NOs.: 38 and 62, (elected species).
Therefore, the instant claims are drawn to a genus of polyclonal antibody or polyclonal and monoclonal antibodies (e.g. HBC34 and variants, instant specification) defined by the CDR sequences that has amino acid variations as claimed by amino acid substitutions (e.g. claim 3) minimum amino acid sequence identity (e.g. claim 9, requires e.g. 90% identity) and thus the genus of the claimed polyclonal or monoclonal antibodies comprise subgenera.
The applicable standard for the written description requirement can be found in MPEP§ 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus.
Amgen Inc. vs Sanofi (2017-1480, Fed Cir, 2017) states that "an adequate written description must contain enough information about the actual makeup of the claim products - a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material," which may be present in "function "terminology "when the art has established a correlation between structure and function" (page 17,1st paragraph).
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description” Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Fri. January 5, 2001, see especially page 1106 column 3).
The applicant has claimed a genus of antibody comprising subgenus that comprise many species due to amino acid substitutions that are claimed for broad function of binding to surface antigen HBV and neutralizing different genotypes of HBV and as well as binding and neutralizing HDV.
It has been well known in the art that minor structural differences even among structurally related compounds or compositions can result in substantially different biological or pharmacological activities. It is known in the art that the substitution of amino acids within the protein sequence may cause the loss of function of the protein. Thus, the large number of sequences encompassed by the current claims may or may not be effective in achieving the binding affinities of the claims. Specifically in relation to CDRs, it should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The structure of a typical antibody molecule. Available from: ncbi.nlm.nih.gov/books/NBK27144/. See entire article). It is also known that single amino acid changes in a CDR can abrogate the antigen binding function of an antibody (Rudikoff et al. Single amino acid substitution altering antigen-binding specificity. Proc Natl Acad Sci U S A. 1982;79(6):1979-1983, see entire article, particularly the abstract and the middle of the left column of page 1982). Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Thus, in view of the reasons set forth above, the instant elected claims (Group I claims) as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 103
14. 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
15. Claims 3 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Corti 2020 (US10683344B2, 06/16/2020 with an earlier priority of 01/17/2019 to the published application US20190016785A1 that claims priority to US15/766,703 filed on 10/07/2016), and further in view of Paul et al 2019 (US10358497B2, 07/23/2019, with an earlier priority to 62/234,546 filed on 09/29/2015), and Thomas et al 2021 (US10982200B2, 04/20/2021, earlier priority of 02/14/2020 to PCT / US2020/018432).
Claims 3, and 15: An antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising a CDRH1 amino acid sequence, a CDRH2 amino acid sequence, and a CDRH3 amino acid sequence; and
a light chain variable region (VL) comprising a CDRL1 amino acid sequence, a CDRL2 amino acid sequence, and a CDRL3 amino acid sequence, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences are according to SEQ ID NOs.: (i) 34, 35, 37, 41, 49, and 55, respectively (elected species),
wherein CDRs are defined according to the CCG numbering system,
wherein, optionally, the VL comprises a R60N substitution mutation, a R60A substitution mutation, a R60K substitution mutation, a S64A substitution mutation, a I74A substitution mutation, or any combination thereof, relative to SEQ ID NO.:58 and wherein the amino acid numbering of the substitution mutation(s) is according to SEQ ID NO.:58, and still further optionally wherein the VL does not comprise any further mutation(s) relative to SEQ ID NO.:58, and wherein the antibody or antigen-binding fragment thereof is capable of binding to the antigenic loop region of HBsAg and, optionally, neutralizing infection by a hepatitis B virus (HBV) of genotype D, A, B, C, E, F, G, H, I, or J, or any combination thereof.
Corti 2020 (US10683344B2) is in the art and teaches antibodies, and antigen binding fragments thereof that bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and potently neutralize infection of both hepatitis B virus (HBV) and hepatitis delta virus (HDV). The invention also relates to epitopes to which the antibodies and antigen binding fragments bind, as well as to nucleic acids that encode and cells that produce such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies and antibody fragments of the invention in the diagnosis, prophylaxis and treatment hepatitis B, and hepatitis D and neutralizes hepatitis B and hepatitis D virus (See, abstract, claim 1).
Corti 2020 (US10683344B2, see entire prior art) teaches SEQ ID NO: 41 (Db) that has 100% sequence amino acid identity with SEQ ID NO: 34 (Qy) of instant claim 3 as shown below:
Qy 1 GRIFRSFYMS 10
||||||||||
Db 26 GRIFRSFYMS 35
Corti 2020 (US10683344B2) teaches SEQ ID NO: 41 (Db) that has 100% sequence amino acid identity with SEQ ID NO: 35 (Qy) of instant claim 3 as shown below:
Qy 1 TINQDGSEKLYVDSVKG 17
|||||||||||||||||
Db 50 TINQDGSEKLYVDSVKG 66
Corti 2020 (US10683344B2) teaches SEQ ID NO: 41 (Db) that has 100% amino acid sequence identity with SEQ ID NO: 37 (Qy) of instant claim 3 as shown below:
Qy 1 WSGNSGGMDV 10
||||||||||
Db 99 WSGNSGGMDV 108
Corti 2020 (US10683344B2, see entire prior art) teaches SEQ ID NO: 42 (Db) that has 92.9% (10/11 amino acid match) amino acid sequence identity with SEQ ID NO: 41 (Qy) of instant claim 3 as shown below:
Query Match 92.9%; Score 52; Length 106;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 SGDKLGNKNVA 11
||||||||||
Db 23 SGDKLGNKNVC 33
Paul et al 2019 (US10358497B2, see entire prior art) teaches an amino acid sequence of an antibody CDR in SEQ ID NO: 3314 (Db) that has one conservative amino acid substitution A 11 S as compared to the instant SEQ ID NO: 41 (Qy) at as shown below.
Qy 1 SGDKLGNKNVA 11
|||||||| |:
Db 1 SGDKLGNKYVS 11
Therefore, the combined teachings of Corti 2020 and Paul et al 2019 teaches the instant SEQ ID NO: 41 because Alanine (A) and Serine (S) can be conservatively substituted.
Corti 2020 (US10683344B2) teaches antibodies, and antigen binding fragments thereof that bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and potently neutralize infection of both hepatitis B virus (HBV) and hepatitis delta virus (HDV). The invention also relates to epitopes to which the antibodies and antigen binding fragments bind (See, abstract). The antibody according to the present invention, or an antigen binding fragment thereof, binds to 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of the HBsAg genotypes A, B, C, D, E, F, G, H, I, and J , and has neutralizing activity against genotypes of HBV and HDV (See, col 19 lines 45-49; Fig. 4, Example 2 col 68-69, Example 5 col 70, col 13 lines 51-60). The teachings disclose the additional limitations of claims 3 and 15.
Thomas et al 2021 (US10982200B2, see entire prior art, 04/20/2021, earlier priority of 02/14/2020 to PCT / US2020/018432) teaches an amino acid sequence of an antibody CDR in SEQ ID NO: 2365 (Db) that has 100% amino acid sequence identity with instant SEQ ID NO: 49 (Qy) at as shown below.
Qy 1 QDSYRPS 7
|||||||
Db 100 QDSYRPS 106
Corti 2020 (US10683344B2) teaches SEQ ID NO: 58 (Db) that has 100% sequence amino acid identity with SEQ ID NO: 55 (Qy) of instant claim 3 as shown below:
Qy 1 QTFDSTTVV 9
|||||||||
Db 1 QTFDSTTVV 9
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings of Corti 2020 (US10683344B2) with additional teachings of Paul et al 2019 (US10358497B2), and Thomas et al 2021 (US10982200B2) on the antibody VH and VL CDR sequences and combine to arrive at the invention of claim 3. The motivation would be to develop a broadly neutralizing antibody that neutralize the claimed HBV genotypes and HDV for therapeutics as recited in the applied prior arts and for commercial success. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 3. There would have been a reasonable expectation of success to arrive at the inventions of claim 3 given the applied prior arts. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), see MPEP § 2143, example of rationales A-G.
16. Claims 9, 23, 30-31, 33-36, and 37-54 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Corti 2020 (US10683344B2, 06/16/2020 with an earlier priority of 01/17/2019 to the published application US20190016785A1 that claims priority to US15/766,703 filed on 10/07/2016), Paul et al 2019 (US10358497B2, 07/23/2019, with an earlier priority to 62/234,546 filed on 09/29/2015), Thomas et al 2021 (US10982200B2, 04/20/2021, earlier priority of 02/14/2020 to PCT / US2020/018432), and further in view of Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018).
Claim 9: The antibody or antigen-binding fragment of claim 3, wherein the VH and the VL comprise or consist of amino acid sequences having at least 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences set forth in SEQ ID NOs: (i) 38 and 62, respectively (elected species).
The combined teachings of Corti 2020 (US10683344B2), Paul et al 2019 (US10358497B2), and Thomas et al 2021 (US10982200B2) teaches claim 3 as recited supra.
The additional teachings of Corti 2020 (US10683344B2), and Corti 2025 (US12304946B2) teaches the added claim limitations of instant claim 9 as recited below.
Corti 2020 (US10683344B2) teaches amino acid sequence represented in SEQ ID NO: 41 that has 100% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 38 of instant claim 9.
Query Match 100.0%; Score 630; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
Qy 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018) teaches amino acid sequence represented in SEQ ID NO: 92 that has 100% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 38 of instant claim 9.
FEATURE:
OTHER INFORMATION: Synthetic sequence HC of HBC34-V35-MLNS and
HBC34-V34-MLNS (g1M17, 1)
Query Match 100.0%; Score 630; Length 449;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
Qy 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018) teaches amino acid sequence represented in SEQ ID NO: 89 (Db) that has 97.2% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 62 (Qy) of instant claim 9.
FEATURE:
OTHER INFORMATION: Synthetic sequence HBC34-V35 VL
Query Match 97.1%; Score 541; Length 106;
Best Local Similarity 97.2%;
Matches 103; Conservative 1; Mismatches 2; Indels 0; Gaps 0;
Qy 1 SYELTQPPSVSVSPGQTVSIPCSGDKLGNKNVAWFQHKPGQSPVLVIYQDSYRPSGIPER 60
||||||||||||||||||||||||||||||||||||||||||||||||: |||||||||
Db 1 SYELTQPPSVSVSPGQTVSIPCSGDKLGNKNVAWFQHKPGQSPVLVIYEVKYRPSGIPER 60
Qy 61 FSGSNSGNTATLTISGTQAMDEAAYFCQTFDSTTVVFGGGTRLTVL 106
||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSNSGNTATLTISGTQAMDEAAYFCQTFDSTTVVFGGGTRLTVL 106
Claim 23: Corti 2025 (US12304946B2) teaches added limitations of instant claim 23, wherein the antibody or antigen-binding fragment is capable of binding to a HBsAg (adw) with an EC50 (ng/ml) of about 3.2 or less, less than 3.0, less than 2.5, less than 2.0, less than 1.5, or less than 1.0, by disclosing is capable of neutralizing (a) an HBV of genotype A with an EC50 of about 2.34 ng/mL; (b) an HBV of genotype B with an EC50 of about 2.22 ng/mL; (c) an HBV of genotype C with an EC50 of about 0.92 ng/mL; (d) an HBV of genotype D with an EC50 of about 1.10 ng/mL; (e) an HBV of genotype E with an EC50 of about 1.12 ng/mL; (f) an HBV of genotype F with an EC50 of about 1.93 ng/mL; (g) an HBV of genotype G with an EC50 of about 1.43 ng/mL; and/or (h) an HBV of genotype H with an EC50 of about 1.93 ng/mL, wherein the EC50 is optionally determined using a recombinant HDV engineered to express an HBsAg of the HBV genotype (See, col 50 line 28-39).
Claim 30: Corti 2025 (US12304946B2) teaches added limitations of instant claim 30, wherein antibody or antigen-binding fragment thereof and a scFv, Fab, or F(ab′)2 fragment (See, col 13 last para, col 14 para 1-2).
Claim 31: Corti 2025 (US12304946B2) teaches added limitations of instant claim 31, wherein antibodies and antigen binding fragments of the present disclosure may, in embodiments, be multispecific (e.g., bispecific, trispecific, tetraspecific, or the like), (See, col 13 last para, col 14 para 1-2).
Claims 33, 36: Corti 2025 (US12304946B2) teaches added limitations of instant claim 33 and 36, wherein a binding protein (e.g., antibody or an antigen binding fragment thereof) of the present disclosure comprises an Fc moiety. In certain embodiments, the Fc moiety may be derived from human origin, e.g., from human IgG1, IgG2, IgG3, and/or IgG4, or from another Ig class or isotype. In specific embodiments, an antibody or antigen binding fragments can comprise an Fc moiety derived from human IgG1 (See, Section on Fc moiety, col 42 lines 1-62).
Claims 34: Corti 2025 (US12304946B2) teaches added limitations of instant claim 34, the Fc moiety may comprise or consist of at least a portion of an Fc moiety that is involved in binding to FcRn binding. In certain embodiments, the Fc moiety comprises one or more amino acid modifications that improve binding affinity for (e.g., enhance binding to) FcRn (See, col 42 lines 1-62).
Claims 35: Corti 2025 (US12304946B2) teaches added limitations of instant claim 35, wherein, it is possible to engineer the Fc moiety to enhance FcγRIIB binding by introducing the mutations (See, col 44 lines 1-23).
Claims 36-37: Corti 2025 (US12304946B2) teaches added limitations of instant claim 36, wherein, antibodies were produced as IgG1 (g1m17, 1 allotype), an antibody, antigen-binding fragment, or Fc region or moiety of the present disclosure comprises a IgG1 allotype g1m17, k1 (See, FIG 1, Example 1, legends for Fig 1 col 2 lines 57-62, col 52 para 2 lines 16-29).
Claims 38-45: Corti 2025 (US12304946B2) teaches added limitations of instant claims 38-45, wherein, in certain embodiments, the Fc moiety comprises or is derived from a IgG Fc and a half-life-extending mutation comprises any one or more of: M428L; N434S; N434H; N434A; N434S; M252Y; S254T; T256E; T250Q; P257I Q311I; D376V; T307A; E380A (EU numbering), (See, col 45, lines 5-63).
Claim 46: Corti 2025 (US12304946B2) teaches added limitations of instant claim 46, wherein, in certain embodiments, a complete Fc moiety comprises a hinge domain, a CH2 domain, and a CH3 domain (e.g., EU amino acid positions 216-446). An additional lysine residue (K) is sometimes present at the extreme C-terminus of the Fc moiety but is often cleaved from a mature antibody (See, col 42, para 2 lines 9-24).
Claims 47-54: Based on the election of the antibody species, claims 47-54 are interpreted to comprise a VH of SEQ ID NO.: 38, comprising HCDRs of SEQ ID NOs.: 34, 35, and 37, and a VL of SEQ ID NO.: 62, comprising LCDRs of SEQ ID NOs.: 41, 49, and 55. The combined prior art teachings as applied to the claims 3, 9 and 45 as recited supra teachings claims 47-54 (See, prior art teachings of Corti 2020 (US10683344B2, Paul et al 2019 US10358497B2, Thomas et al 2021 US10982200B2, and further in view of Corti 2025 US12304946B2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Corti 2020 (US10683344B2), Paul et al 2019 (US10358497B2), and Thomas et al 2021 (US10982200B2) with additional teachings of Corti 2025 (US12304946B2) and Corti 2025 (US12304946B2) to arrive at the invention of claims 9, 23, 30-31, and 33-54. The motivation would be to develop a broadly neutralizing antibody that neutralize the claimed HBV genotypes and HDV for therapeutics as recited in the applied prior arts and for commercial success. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 9, 23, 30-31, and 33-54. There would have been a reasonable expectation of success to arrive at the inventions of claims 9, 23, 30-31, and 33-54 given the applied prior arts. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), see MPEP § 2143, example of rationales A-G.
17. Claims 13, 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Corti 2020 (US10683344B2, 06/16/2020 with an earlier priority of 01/17/2019 to the published application US20190016785A1 that claims priority to US15/766,703 filed on 10/07/2016), Paul et al 2019 (US10358497B2, 07/23/2019, with an earlier priority to 62/234,546 filed on 09/29/2015), Thomas et al 2021 (US10982200B2, 04/20/2021, earlier priority of 02/14/2020 to PCT / US2020/018432), as applied to claim 3, and further in view of Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018).
Claim 9: The antibody or antigen-binding fragment of wherein the VH and the VL comprise or consist of the amino acid sequences set forth in SEQ ID NOs.: (i) 38 and 62, respectively (elected species).
The combined teachings of Corti 2020 (US10683344B2), Paul et al 2019 (US10358497B2), and Thomas et al 2021 (US10982200B2) teaches claim 3 as recited supra.
The additional teachings of Corti 2020 (US10683344B2), and Corti 2025 (US12304946B2) teaches the added claim limitations of instant claim 13 as recited below.
Corti 2020 (US10683344B2) teaches amino acid sequence represented in SEQ ID NO: 41 that has 100% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 38 of instant claim 9.
Query Match 100.0%; Score 630; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
Qy 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018) teaches amino acid sequence represented in SEQ ID NO: 92 that has 100% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 38 of instant claim 9.
FEATURE:
OTHER INFORMATION: Synthetic sequence HC of HBC34-V35-MLNS and
HBC34-V34-MLNS (g1M17, 1)
Query Match 100.0%; Score 630; Length 449;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
Qy 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018) teaches amino acid sequence represented in SEQ ID NO: 89 (Db) that has 97.2% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 62 (Qy) of instant claim 9.
FEATURE:
OTHER INFORMATION: Synthetic sequence HBC34-V35 VL
Query Match 97.1%; Score 541; Length 106;
Best Local Similarity 97.2%;
Matches 103; Conservative 1; Mismatches 2; Indels 0; Gaps 0;
Qy 1 SYELTQPPSVSVSPGQTVSIPCSGDKLGNKNVAWFQHKPGQSPVLVIYQDSYRPSGIPER 60
||||||||||||||||||||||||||||||||||||||||||||||||: |||||||||
Db 1 SYELTQPPSVSVSPGQTVSIPCSGDKLGNKNVAWFQHKPGQSPVLVIYEVKYRPSGIPER 60
Qy 61 FSGSNSGNTATLTISGTQAMDEAAYFCQTFDSTTVVFGGGTRLTVL 106
||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSNSGNTATLTISGTQAMDEAAYFCQTFDSTTVVFGGGTRLTVL 106
Claims 16 and 18 (dependent on claim 3): The added limitations of claims 16 and 18 on the characteristic of an antibody or antigen-binding fragments thereof comprising the claimed VH and VL SEQ ID NO: 38 and 62 comprising the mutations recited in instant claim 3 and reduced dimer formation are obvious in view of the prior arts as applied to render obvious the instant claim 3 as recited supra, and additionally comprising antibody with reduced dimer formation is a design choice for the composition and the antibody therapeutic against HBV and HDV.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Corti 2020 (US10683344B2), Paul et al 2019 (US10358497B2), and Thomas et al 2021 (US10982200B2) with additional teachings of Corti 2025 (US12304946B2) and Corti 2025 (US12304946B2) to arrive at the invention of claims 13, 16 and 18. The motivation would be to develop a broadly neutralizing antibody that neutralize the claimed HBV genotypes and HDV for therapeutics as recited in the applied prior arts and for commercial success. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 13, 16 and 18. There would have been a reasonable expectation of success to arrive at the inventions of claims 13, 16 and 18 given the applied prior arts. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), see MPEP § 2143, example of rationales A-G.
18. Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Corti 2020 (US10683344B2, 06/16/2020 with an earlier priority of 01/17/2019 to the published application US20190016785A1 that claims priority to US15/766,703 filed on 10/07/2016), and further in view of Paul et al 2019 (US10358497B2, 07/23/2019, with an earlier priority to 62/234,546 filed on 09/29/2015), Thomas et al 2021 (US10982200B2, 04/20/2021, earlier priority of 02/14/2020 to PCT / US2020/018432), Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018).
Claim 14: An antibody or antigen-binding fragment, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and the VL comprise or consist of the amino acid sequences set forth in SEQ ID NOs.: (i) 38 and 62, respectively (elected species).
The combined teachings of Corti 2020 (US10683344B2), Paul et al 2019 (US10358497B2), and Thomas et al 2021 (US10982200B2) and Corti 2025 (US12304946B2) teaches claim 14 limitations as recited below.
Corti 2020 (US10683344B2) teaches amino acid sequence represented in SEQ ID NO: 41 that has 100% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 38 of instant claim 9.
Query Match 100.0%; Score 630; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
Qy 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018) teaches amino acid sequence represented in SEQ ID NO: 92 that has 100% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 38 of instant claim 9.
FEATURE:
OTHER INFORMATION: Synthetic sequence HC of HBC34-V35-MLNS and
HBC34-V34-MLNS (g1M17, 1)
Query Match 100.0%; Score 630; Length 449;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ELQLVESGGGWVQPGGSQRLSCAASGRIFRSFYMSWVRQAPGKGLEWVATINQDGSEKLY 60
Qy 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDSVKGRFTISRDNAKNSLFLQMNNLRVEDTAVYYCAAWSGNSGGMDVWGQGTTVSVSS 119
Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018) teaches amino acid sequence represented in SEQ ID NO: 89 (Db) that has 97.2% amino acid sequence identity with amino acid sequence of instant SEQ ID NO: 62 (Qy) of instant claim 9.
FEATURE:
OTHER INFORMATION: Synthetic sequence HBC34-V35 VL
Query Match 97.1%; Score 541; Length 106;
Best Local Similarity 97.2%;
Matches 103; Conservative 1; Mismatches 2; Indels 0; Gaps 0;
Qy 1 SYELTQPPSVSVSPGQTVSIPCSGDKLGNKNVAWFQHKPGQSPVLVIYQDSYRPSGIPER 60
||||||||||||||||||||||||||||||||||||||||||||||||: |||||||||
Db 1 SYELTQPPSVSVSPGQTVSIPCSGDKLGNKNVAWFQHKPGQSPVLVIYEVKYRPSGIPER 60
Qy 61 FSGSNSGNTATLTISGTQAMDEAAYFCQTFDSTTVVFGGGTRLTVL 106
||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSNSGNTATLTISGTQAMDEAAYFCQTFDSTTVVFGGGTRLTVL 106
Corti 2020 (US10683344B2) teaches antibodies, and antigen binding fragments thereof that bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and potently neutralize infection of both hepatitis B virus (HBV) and hepatitis delta virus (HDV). The invention also relates to epitopes to which the antibodies and antigen binding fragments bind (See, abstract). The antibody according to the present invention, or an antigen binding fragment thereof, binds to 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of the HBsAg genotypes A, B, C, D, E, F, G, H, I, and J , and has neutralizing activity against genotypes of HBV and HDV (See, col 19 lines 45-49; Fig. 4, Example 2 col 68-69, Example 5 col 70, col 13 lines 51-60.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings of Corti 2020 (US10683344B2) with additional teachings of Paul et al 2019 (US10358497B2), Thomas et al 2021 (US10982200B2) and Corti 2025 (US12304946B2) and Corti 2025 (US12304946B2) to arrive at the invention of claim 14. The motivation would be to develop a broadly neutralizing antibody that neutralize the claimed HBV genotypes and HDV for therapeutics as recited in the applied prior arts and for commercial success. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 14. There would have been a reasonable expectation of success to arrive at the inventions of claim 14 given the applied prior arts. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), see MPEP § 2143, example of rationales A-G.
Double Patenting
19. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is autoprocessed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
20. Claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 21-22, 52-54 of copending Application No. 19/318,167 in view of combined prior art teachings of Corti 2020 (US10683344B2, 06/16/2020 with an earlier priority of 01/17/2019 to the published application US20190016785A1 that claims priority to US15/766,703 filed on 10/07/2016), Paul et al 2019 (US10358497B2, 07/23/2019, with an earlier priority to 62/234,546 filed on 09/29/2015), Thomas et al 2021 (US10982200B2, 04/20/2021, earlier priority of 02/14/2020 to PCT / US2020/018432), Corti 2025 (US12304946B2, 05/20/2025 with an earlier priority to US 62/782,274 filed on 12/19/2018).
The instant claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 and co-pending claims 1-4, 21-22, 52-54 are directed to an antibody, or an antigen binding fragment thereof, inter alia, that binds to the antigenic loop region of HBsAg and neutralizes infection with hepatitis B virus and hepatitis delta virus. The instant claims 3, 9, 13-16, 18, 23, 30-31 and 33-54 recited amino acid sequences of VH and VL CDRs whereas the co-pending claims are very broad and does not recite the amino acid sequences of VH and VL CDRs. The combined prior art teachings as applied and recited supra for obviousness rejection of the claims under 35 U.S.C. 103 renders obvious the amino acid sequences of VH and VL CDRs that can be used to construct the claimed broadly reactive antibodies with a reasonable expectation of success, and one of the ordinary skills would be motivated to do so for developing anti-HBV and anti-HDV therapeutics for commercial success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
21. No claim is allowed.
22. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMADHAN JAISING JADHAO/ Examiner, Art Unit 1672
/BENNETT M CELSA/ Primary Examiner , Art Unit 1600