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 .
Election/Restrictions
Applicant’s election without traverse of Group I and tixagevimab in the reply filed on 03/25/2026 is acknowledged.
Claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 4 and 6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/25/2026.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of Claims
Claims 1-20 are pending. Claims 4, 6, and 15-20 have been withdrawn from further consideration. Claims 1-3, 5, and 7-14 will be examined on the merits.
Priority
Provisional application 63/422,238 is acknowledged as disclosing the claimed invention and the effective filing date is 11/03/2022.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/31/26 has been considered. Signed copies are enclosed.
Claim Objections
Claim 8 is objected to because of the following informalities: Claim 8 does not recite SEQ ID NO: 34, which is the elected full length heavy chain nucleotide sequence. Appropriate correction is required.
Claim Interpretation
Claim 1 recites “(i) an amino acid sequence of a heavy chain variable region of tixagevimab” and “(iii) an amino acid sequence of a light chain variable region of tixagevimab”. As disclosed in Table 2 of the specification and in the election response filed on 03/25/2026, these are sequences are interpreted as SEQ ID NO: 8 and SEQ ID NO: 10, respectively.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 depends on claim 1, which recites a monoclonal antibody comprising an amino acid sequence of a heavy chain variable region of tixagevimab and an amino acid sequence of a light chain variable region of tixagevimab, which are SEQ ID NOs: 8 and 10, respectively, as recited above. Claim 3 recites a monoclonal antibody comprising a heavy chain with 70% sequence identity to the amino acid sequence of SEQ ID NO: 8 and a light chain with 70% sequence identity to the amino acid sequence of SEQ ID NO: 10, which is broader in scope than claim 1. Therefore, claim 3 expands the scope of claim 1, and does not further limit it. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 3 and 8 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.
Claim 3 recites a monoclonal antibody comprising a heavy chain with 70% sequence identity to the amino acid sequence of SEQ ID NO: 8 and a light chain with 70% sequence identity to the amino acid sequence of SEQ ID NO: 10. The specification teaches two antibodies with specific heavy and light chain sequences that bind to and neutralize SARS-CoV-2 virus, referred to as ‘tixagevimab’ and ‘cilgavimab’, as well as a variant of these antibodies with signal peptides appended on the end of the protein. The specification also recites, in paragraph [0065], "sequence identity" refers to the percent of nucleotides/amino acid residues in a subject sequence that are identical to nucleotides/amino acid residues in a reference sequence, after aligning the sequences". There is no evidence from the disclosure that any antibodies with substitutions of any kind within the CDRs of the disclosed antibodies were made. Neither instant claim 3 nor the specification teaches that any particular part of the sequence must be conserved when determining if an antibody has 70% sequence identity. As is widely accepted in the art, the CDRs of an antibody are considered vital for binding. As claim 3 does not recite that the antibody must have limited or no substitutions in the CDRs, one cannot reasonably conclude that the resulting antibody with 70% sequence similarity will have the same function (i.e. will bind to and neutralize SARS-CoV-2) as the antibodies with the recited SEQ ID NOs. Therefore, claim 3 is drawn to a broad genus of antibodies with 70% sequence identity to SEQ ID NOs 8 and 10, that are not required to have a common function.
The monoclonal antibody of claim 1 meets the written description requirement of USC 112(a). The monoclonal antibodies of claim 3, wherein the amino acid sequence of the light chain variable region of tixagevimab has at least 70%, at least 80% or at least 90% sequence identity to SEQ ID NO: 10 and/or wherein the amino acid sequence of the heavy chain variable region of tixagevimab has at least 70%, at least 80%, or at least 90% sequence identity to SEQ ID NO: 8 do not meet the written description requirements set forth in USC 112(a).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
To fulfill the written description requirements set forth under 35 U.S.C. 112(a), the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession of the claimed invention. To adequately describe the genus of antibodies, Applicant must adequately describe which combination of variable regions and framework regions that give rise to an antibody with the claimed immunological function. The instant specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the antibody and its recited function (neutralizing SARS-CoV-2), so that the skilled artisan could immediately envision, or recognize, at least a substantial number of members of the claimed genus of antibodies. The specification fails to disclose which amino acids might be added, replaced or deleted within the 70% sequence identity requirement so that the resultant antibody retains the binding specificity of its parent, or by which other amino acids the essential amino acids might be replaced so that the resultant antibody retains the binding specificity of its parent. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of antibodies to which the claims refer; and accordingly, the specification fails to adequately describe at least a substantial number of members of the claimed genus of antibodies.
As evidenced by the teachings below, the art is unpredictable. Skolnick et al. (Trends in Biotechnology (2000) 18:34-39) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily bind to a given antibody.
As stated above, the CDRs are vital for antigen binding, as evidenced by Kapingidza et al. (Vertebrate and invertebrate respiratory proteins, lipoproteins and other body fluid proteins, 2020, 465-497) (see page 468, lines 1-4, and pages 476-482). Sela-Culang et al. (Frontiers in immunology, 2016, 4:302.) expands on the importance of antibody sequence and function, explaining that amino acid residues outside of the CDRs can influence antigen binding (abstract, whole document). Additionally, Clark et al. (Journal of Structural Biology, 2014, 185(2), 223-227) show that mutational effects on interfaces are often unpredictable (see pg. 223, 2nd col. 1st full para), and that it is easy to damage an interface and decrease binding affinity. Therefore, a person of ordinary skill in the art at the time of filling would understand residues within the CDRs are integral to antigen binding or maintaining the structure of the region that binds to the antigen and substitutions in these regions would affect one or both these attributes. As there is no art-recognized correlation between structure and function, it would be impossible for one of ordinary skill in the art to predict which variable CDRs, combinations of CDRs, or combinations of particular substitutions, would result in a structure that binds to and neutralizes SARS-CoV-2.
Overall, based on the disclosure, the state of the art at the time of filing, a skilled artesian would have recognized that the applicant was not in possession of the claimed invention at the time of filing. Consequently, in accordance with the MPEP, only the antibody comprising the amino acid sequences of SEQ ID NOs 8 and 10, not the full breadth of claim 3 regarding any amino acid sequence having at least 70% sequence identity to these SEQ ID NOs, meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is severable from its enablement provision. (See page 1115).
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.
Claim(s) 1-3, 5, and 8-9 are is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2023064841 A1, Weiner et al. (EFD 10/13/2021).
The instant claims are drawn to a monoclonal antibody comprising an IgG heavy chain backbone sequence (such as SEQ ID NO: 1), a heavy chain variable region (VH) of tixagevimab (SEQ ID NO: 8), and a light chain variable region (VL) of tixagevimab (SEQ ID NO: 10), as well as a nucleic acid encoding the same (at least 70% identity to SEQ ID NOs 34 and 38, respectively). Claim 5 recites that the entire heavy chain comprises SEQ ID NO: 20 and the entire light chain comprises SEQ ID NO: 16. SEQ ID:20 is noted to contain both SEQ ID NO: 1 and SEQ ID NO: 8.
Weiner et al. disclose a monoclonal antibody with the heavy chain of SEQ ID NO: 20 (Weiner SEQ ID NO: 4) and the light chain of SEQ ID NO: 16 (Weiner SEQ ID NO: 66). Weiner further disclose a sequence that comprises both SEQ ID NO: 16 and SEQ ID NO:20 in Weiner SEQ ID NO: 81, identified as the heavy chain and light chain of an antibody in a single construct on page 156. Therefore, Weiner et al. discloses a monoclonal antibody that meets the limitations of instant claims 1, 2, 3, and 5. Page 54 discloses a nucleic acid molecule that encodes SEQ ID NO: 81, and a single plasmid, or vector, that contains SEQ ID NO: 82, which comprises a sequence with 74.2% identity to SEQ ID NO: 34 and 73.6% identity to SEQ ID NO: 38. Therefore, Weiner et al. discloses a nucleic acid and a vector that meets the limitations of instant claims 8 and 9. Thus, Weiner et al. anticipates instant claims 1-3, 5, and 8-9.
Claim Rejections - 35 USC § 103
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.
Claims 1, 3, 5, and 7-14 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2023064841 A1, Weiner et al. (EFD 10/13/2021) in view of Jansing et al., (2019) Plant Biotechnol J 17(2):350–361.
The instant claims are drawn to a monoclonal antibody comprising an IgG heavy chain backbone sequence (such as SEQ ID NO: 1), a heavy chain variable region (VH) of tixagevimab (SEQ ID NO: 8), and a light chain variable region (VL) of tixagevimab (SEQ ID NO: 10), as well as a nucleic acid encoding the same (at least 70% identity to SEQ ID NOs 34 and 38, respectively). Claim 5 recites that the entire heavy chain comprises SEQ ID NO: 20 and the entire light chain comprises SEQ ID NO: 16. SEQ ID:20 is noted to contain both SEQ ID NO: 1 and SEQ ID NO: 8. Claim 7 recites the glycosylation form of the antibody as GnGn or MGn. Claims 10-12 recite a Nicotiana benthamiana plant with reduced expression of XylT and/or FucT that contains the nucleic acid construct of claim 8. Claim 13 recites a monoclonal antibody made from this plant, and claim 14 recites a pharmaceutical composition comprising this antibody and a carrier, diluent, or excipient.
Weiner et al. disclose a monoclonal antibody with the heavy chain of SEQ ID NO: 20 (Weiner SEQ ID NO: 4) and the light chain of SEQ ID NO: 16 (Weiner SEQ ID NO: 2). Weiner further disclose a sequence that comprises both SEQ ID NO: 16 and SEQ ID NO:20 in Weiner SEQ ID NO: 81, identified as the heavy chain and light chain of an antibody in a single construct on page 156. Therefore, Weiner et al. discloses a monoclonal antibody that meets the limitations of instant claims 1, 2, 3, and 5. Page 54 discloses a nucleic acid molecule that encodes SEQ ID NO: 81, and a single plasmid, or vector, that contains SEQ ID NO: 82, which comprises a sequence with 74.2% identity to SEQ ID NO: 34 and 73.6% identity to SEQ ID NO: 38. Therefore, Weiner et al. discloses a nucleic acid and a vector that meets the limitations of instant claims 8 and 9. Thus, Weiner et al. teaches instant claims 1-3, 5, and 8-9. Weiner et al. also teaches a pharmaceutical composition of this antibody on page 81, lines 17-19, wherein the composition may further comprise a pharmaceutically acceptable excipient such as a carrier or a diluent.
Weiner et al. does not teach producing this antibody in a plant. Weiner et al. also does not teach the glycoform of the antibody.
Jansing et al. teaches a transgenic N. benthamiana plant deficient in XylT and FucT activity that expresses a monoclonal antibody (2G12) (see abstract). The antibody expressed in these plant lines was characterized by a GnGn glycoform (see page 357, second paragraph). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the invention, to express the construct of Weiner et al. in the transgenic N. benthamiana plant of Jansing et al. in order to make the antibody recited in the claimed invention. One would be motivated to do so because, as Jansing et al. teaches on page 356, first paragraph under Discussion, N. bethamiana is a widely used species in the production of proteins, because expression of the transgenic proteins occurs fast and has a high yield of over 2 mg/g of leaf, a higher yield than in mammalian cells. One would have reasonable expectation of success, as Jansing et al. teaches, at the bottom of page 357 into page 358, that antibodies produced in these cell lines displays a comparable affinity for the antibody target as those produced in the ‘gold standard’ CHO cells. Because Jansing et al. teaches a fast, efficient, and optimal method of producing antibodies, it would be obvious to one of ordinary skill in the art to use this form of production to manufacture any known antibody construct. Therefore, the claimed invention is prima facie obvious as exemplified by the known antibody of Weiner et al. in view of Jansing et al.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US 2021/0300999 A1, Crowe et al., published 9/30/2021: discloses an antibody with VH of SEQ ID NO: 8 and VL of SEQ ID NO: 10, anticipates 1 and 3.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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