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 1-34 are the original claims filed 3/21/2023. In the Preliminary Amendment of 3/21/2023, claims 1-4, 6-13, 19 and 23 are amended and claims 20, 24-25 and 34 are canceled. Claims 1-19, 21-23, and 26-33 are the pending claims.
Priority
2. USAN 18/027,583, filed 03/21/2023, is a National Stage entry of PCT/US2021/ 051165, International Filing Date: 09/21/2021, PCT/US2021/051165 Claims Priority from Provisional Application 63/081,315, filed 09/21/2020, and PCT/US2021/ 051165 Claims Priority from Provisional Application 63/109,877, filed 11/05/2020.
Original description support for the humanized cetuximab clones H1-H11 is found in Provisional Application 63/109,877, filed 11/05/2020.
Information Disclosure Statement
3. As of 10/9/2025, no IDS is filed for this application.
4. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objections
Specification
5. The disclosure is objected to because of the following informalities:
a) The disclosure is objected to because it contains five embedded hyperlinks and/or other form of browser-executable codes. See “https.” 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.
b) The use of the term, i.e., ATCC, Tween, Triton, Tris, MabSelect, HisTrap, Octet, Expifectamine, OptiPRO, ExpiCHO, Clariostar, DynaPro, GraphPad, Vi-Cell, Acquity, Geneious, 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.
c) The figure legend to Figure 1 is objected to for failing to include the sequence identifier (SEQ ID NO) for the corresponding peptide sequence > 4 amino acids in length shown in the figure. See 37 CFR 1.821-1.825.
d) The specification is objected to for peptide sequences > 4 amino acids in length that are not identified by sequence identifier (SEQ ID NO) pursuant to 37 CFR 1.821-1.825. See “(G4S)4” in Example 4. Also see the peptides TVSS, TVSA, LTVL and LELK.
Appropriate correction is required.
Claim Objection
6. Claims 6, 9-12, 14, 17, 19, 23 and 32-33 are objected to because of the following informalities:
a) Amend claim 6 to replace “a Fc domain” with “[a] an Fc domain.”
b) Claims 9-12, 17 and 23 are objected to for inconsistency with respect to the grouping of sequences.
Claim 9 drawn to a monospecific antibody recites “SEQ ID NO. 137, 139; 141, 143; 141, 149, 151, 139; 145, or 147.” The punctuation is confusing as to why semi-colons and commas are interspersed in the claim when the sequences clearly correspond to HC/LC from specific clones
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Claim 10 drawn to a bispecific antibody recites “SEQ ID NO. 137, 145, 139, 147, 141, 145, 143, 147, 141, 145, 149, 147, 151, 145, 139, or 147.” The punctuation is confusing when the sequences clearly correspond to HC/LC from specific clones. Compare claim 10 to claim 17 for a bispecific antibody that is presented with different punctuation but the same sequences: “SEQ ID NO. 137, 145, 139, 147; 141, 145, 143, 147; 141, 145, 149, 147; 151, 145, 139, or 147.”
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Claim 11 drawn to a penta-specific antibody recites “SEQ ID NO. 85, 87; 89, 91; 93, 95, 97, 99, 101, 103, 105, 107.” The punctuation is confusing as to why semi-colons and commas are interspersed in the claim when the sequences clearly correspond to HC/LC from specific clones
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Claim 12 drawn to a hexa-specific antibody recites “SEQ ID NO. 109, 111, 113, 115, 117 or 119.” The punctuation is confusing when the sequences clearly correspond to HC/LC from specific clones
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Claim 23 is drawn to penta-miniGNC proteins reciting “SEQ ID NO 121, 123, 125, 127, 129, 131, 133, 135, or a combination thereof.” The punctuation is confusing when the sequences clearly correspond to HC/LC from specific clones and where combinations thereof are not taught in the specification
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c) Amend Claim 17 to replace: “a N-terminus and a C-terminus” with “[a] an N-terminus and a C-terminus”; “the N-terminal” with “the N-terminus”; and “the C-terminal” with “the terminus.”
d) Amend Claim 19 to replace: “a N-terminus and a C-terminus” with “[a] an N-terminus and a C-terminus”
e) Amend claim 32 to reduce the excess verbiage as follows:
A method for treating or preventing a cancer, an autoimmune disease, or an infectious disease in a subject, said method comprising administering to the subject a pharmaceutical composition of claim 29. The amendment would not change the scope of the claim.
f) Claim 33 is objected to because the claim makes reference to two claims drawn to different features, claims 7 and 9 (MPEP 608.01(n)).
Appropriate correction is required.
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.
7. Claims 19, 27 and 33 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) Claim 19 recites the limitation "the multi-specific antibody-like protein". There is insufficient antecedent basis for this limitation in the claim. Claim 7 from which claim 19 depends makes NO reference to the antibody-like protein being multispecific.
b) Claim 27 recites the limitation "sequences". Claim 27 is drawn to more than one nucleic acid sequence. There is insufficient antecedent basis for this limitation in the claim. In depending from claim 26, only a single nucleic acid sequence is provided for encoding the antibody-like protein of claim 7.
c) Claim 33 recites the limitation "the DNA sequence encoding the antibody-like protein of Claim 9". There is insufficient antecedent basis for this limitation in the claim. Claim 9 is drawn to a protein and not a nucleic acid much less a DNA. The host cell of claim 28 is drawn to the isolated nucleic acid sequence of claim 26.
d) Claim 33 recites the limitation "said multi-specific antibody-like protein". There is insufficient antecedent basis for this limitation in the claim. Neither claims 7 or 9 from which claim 33 depends make any reference to the antibody-like protein being multispecific.
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.
8. Claim 4 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 4 is drawn to the human EGFR binding peptide comprising the sequence having at least 98% identity to SEQ ID NO 57 and having at least one end of the scfv domain comprising a histidine residue. The specification teaches the sequence of SEQ ID NO 57 comprises a scfv-His residue
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. Claim 4 depends from claim 3 that is drawn to a sequence at least 98% identical to the sequence of SEQ ID NO 57 and that comprises a scfv-His residue on at least one end.
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.
Written Description
9. Claims 1-19, 21-23, and 26-33 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 interpretation
Claims 1-6 are drawn to a peptide having a binding specificity to human EGFR wherein the peptide comprises single VH domain sequences having at least 98% identity to SEQ ID NOS: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, or 41, single VL domain sequences having at least 98% identity to SEQ ID NOS: 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, or 43 (Claim 1), and scfv (VH/VL) sequences having 98% identity to SEQ ID NOS: 57, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, or 83 (Claims 2-6).
Claims 7-19, 21-23 and 26-33 are drawn to an antibody-like protein comprising VH domain sequences having at least 98% identity to SEQ ID NOS: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, or 41, and VL domain sequences having at least 98% identity to SEQ ID NOS: 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, or 43 (claim 7), and scfv (VH/VL) sequences having 98% identity to SEQ ID NOS: 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, or 83 (Claim 8). Claims 9-12 are drawn to mono-, bi-, penta- and hexa-specific antibodies, respectively. The heavy and light chains of the antibody-like protein comprise sequences at least 98% identical to the HC of SEQ ID NOS: 85, 89, 93, 97, 101, 105, 109. 113, 117, 137, 141, 145, or 151 and sequences at least 98% identical to the LC of SEQ ID NOS: 87, 91, 95, 99, 103, 107, 111, 115, 119, 139, 143, 147, or 149 (claim 13).
Claim 32 is drawn to administering the antibody-like protein of claim 7 to any subject having any cancer, autoimmune or infectious disease in the absence of a correlation between EGFR expression and the cancer, autoimmune or infectious disease much less where the antibody-like protein is therapeutic (treatment effective) and prophylactic (preventative).
The interpretation encompasses a genus of EGFR-binding peptide variants and antibody-like protein variants beyond those taught in the specification. Because applicant seeks patent protection for all such anti-EGFR binding moieties, this genus must be adequately described.
A description adequate to satisfy 35 U.S.C. § 112(a) must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed (Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). The 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’s specification” (In re Katz Interactive Call Processing Patent Litig. 639 F.3d 1303, 1319 (Fed. Cir 2011).
Scope of the claimed genus
The specification does not define the meaning of “at least 98% sequence identity”, per se. The percent variation may encompass insertions, deletions and/or substitutions. Any number and kind of amino acid that is natural, non-natural or even a mimetic fall within the meaning of the phrase. The percent variation may encompass non-naturally occurring thiol groups, e.g., methionine or cysteine, which is potentially disadvantageous because these amino acids can lead to misfolding or mis-conjugation problems.
Here, all of the claims encompass anti-EGFR binding peptide or antibody-like proteins with potential variations to the VH and/or VL domains, in which the variable domains, including the complementarity determining regions (CDRs) could vary relative to the VLC and VHC and CDRs found a parental antibody VH or VL in addition to the VL frameworks and VH frameworks. The encompassed EGFR binding moieties are allowed to vary relative to the parental VH and/or VL at any position. The genus encompassed by the claims is therefore very large and there is substantial variation within the genus.
Claim 32 not only encompasses all of the herein above-mentioned variants for the EGFR-binding moiety but the requirement that the variants mediate a therapeutic and prophylactic effect in the subject based on anyone of the sequence variants.
State of the Relevant Art
AS regards claim 1 drawn to single VH or single VL domains, it was well-established in the art that the formation of an intact antigen-binding surface on an antibody required the association of the complete heavy and light chain variable regions, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Franssen, Frontiers in Bioscience, 13:1619-33 (2008) (PTO-892) (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). While this overall architecture is shared among antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level, even when the same antigen is bound (Edwards et al., J Mol Biol 334:103-118 (2003) (PTO-892); see also Marchalonis et al., Dev & Comp Immunol. 30:223-247 (2006) (PTO-892), summarized in Abstract and Conclusion.
AS regards the breadth and scope of the VH/VL domain variants (“at least 98% sequence identity”) of Claims 1-19, 21-23, and 26-33, methods of preparing antibodies from a variety of species to a protein or peptide of interest were well-established in the art at the time the application was filed. But application of those methods to any given antibody was still a matter of trial-and-error testing, and the skilled person could not automatically predict which residues in the CDRs would be tolerant of mutations, or which amino acid modifications would maintain antigen binding. Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. For example, it is generally the case that absent the fundamental structure provided for by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, a person of ordinary skill cannot visualize or otherwise predict, what an antibody with a particular set of functional properties would look like structurally.
Moreover, persons of ordinary skill in the art have long since acknowledged that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function. Moreover, persons of ordinary skill in the art have long since acknowledged that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function. Lippow, for example, teaches that a single point mutation in the CDR of a parent antibody led to as much as an eightfold improvement in binding affinity in the resulting mutant (p. 1172, left col., lines 7-8 from end of first full paragraph and Table 1a) (Lippow et al., “Computational design of antibody-affinity improvement beyond in vivo maturation,” Nature Biotechnology, 25(10):1171-1176 (2007) (PTO-892).
Sulea teaches that individual point mutations gave an improvement of one order of magnitude in binding affinity, which in turn, generated a 6-fold enhancement of efficacy at the cellular level (Abstract) (Sulea et al., “Application of Assisted Design of Antibody and Protein Therapeutics (ADAPT) improves efficacy of a Clostridium difficile toxin A single-domain antibody," Scientific Reports, 8(260):1-11 (2018) (PTO-892). Hasegawa et al. reports that a single amino acid substitution in the variable region was sufficient to alter the efficiency of biosynthesis and the variant antibody acquired stronger binding affinity to its antigen than the parent (Hasegawa et al., “Single amino acid substitution in LC-CDR1 induces Russell body phenotype that attenuates cellular protein synthesis through elF2a phosphorylation and thereby downregulates IgG secretion despite operational secretory pathway traffic,” MABS, VOL. 9, NO. 5, pp. 854-873 (2017) (PTO-892)). Altshuler teaches that generally, “CDR mutations should not involve residues that can play structural functions (form parts of the domain ‘internal core’, internal salt bridges, hydrogen bonds, etc.).” “Usually these are conservative residues, and any substitution of these residues causes decrease[s] in affinity” (Altshuler et al., “Generation of Recombinant Antibodies and Means for Increasing Their Affinity,” Biochemistry (Moscow), 75(13):1584-1605 (2010) at p. 1600, col. 1, para. 2, lines 1-5 (PTO-892). Accordingly, a person of ordinary skill in the art would have recognized that it was highly unpredictable that any of the CDRs or FRs could be modified to create an unlimited change in amino acids for both the CDRs and FRs of the claimed EGFR binding peptides/EGFR antibody-like proteins, without increasing, eliminating, or in some way altering antigen binding.
Summary of species disclosed in the specification
The specification specifically teaches …”cetuximab was humanized with the goals of removing post- translational modification sites, stabilizing the antibody, and reducing the potential for immunogenicity while retaining high affinity for EGFR. Strategies for humanization included a straight CDR graft onto a stable human framework, sequence-guided grafting onto the most similar germline or consensus framework, and a structure-guided approach based on predicted stability effects of humanizing mutations.”
The specification teaches 11 humanized cetuximab clones, H1-H11, with VH/VL domains shown as those instant claimed:
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The specification teaches 12 humanized cetuximab scfv clones, SI-79SF1-SI-79SF13, with VH/VL domains shown as those instant claimed:
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Applicant’s specification fully discloses 11 antibody clones derived from the art-known mouse anti-EGFR antibody, cetuximab. None of the corresponding VH nor VL domains from any one clones are shown to bind EGFR as single domain format. None of the corresponding VH nor VL domains from any one clone are shown to engineered as a variant thereof having “at least 98% identity” and that maintains EGFR binding activity.
Are the disclosed species representative of the claimed genus?
It is asserted that the disclosed species are not representative of the claimed genus because the claims encompass all amino acid variation so long as the sequence is at least 98% identical to the parent CDR and frameworks for the claims VH and VL domains. The genus of all possible anti-EGFR binding moieties encompassed by the claimed VH and VL variation would be structurally distinct but unpredictable whether the structure/function correlation was met for binding to EGFR. The specification does not identify which VHCDRs or VLCDRs, which combination of fewer than all six CDRs, or which subset of residues in the combination of CDRs is essential for the recited function of binding EGFR. Neither the specification nor the prior art provides guidance as to what structural changes can be made to the parent sequences and still predictably arrive at an antibody that binds EGFR. The disclosed species therefore do not represent the claimed genus.
Has Applicant provided a common structure sufficient to visualize the genus?
Applicant has not provided a common structure sufficient to visualize the genus of all possible functional variants. One of ordinary skill in the art would have understood that clones H1-H11 functioned similarly, but would not have known which residues could have been modified while still maintaining EGFR selectivity and affinity, which could be conservatively changed much less which could not be changed at all.
While the prior art contains disclosure as to the structural features of several anti- EGFR antibodies, it is unclear what structural features these antibodies need to share in order to maintain binding affinity and stability. Even in 2021, antibodies are still not understood well enough to allow researchers to predict with certainty what modifications can be made to a primary antibody sequence such that binding is maintained. “[T]he major test of understanding is whether the changes associated with antibody maturation can be predicted with any reasonable accuracy, and whether there is sufficient information for developing therapeutic antibodies,” Vajda et al., “Progress toward improved understanding of antibody maturation,” Current Opinion in Structural Biology, 67 pp. 226-231 (2021 (PTO 892)) at p. 226, col. 2, lines 20-24.
As recently as 2020, researches were still speculating as to how to reliably identify further putative binders from antibody sequence data, see, e.g., Marks et al., “How repertoire data are changing antibody science,” J. Biol. Chem. 295(29) 9823-9837 (2020 (PTO 892)), acknowledging that “there is a vast amount of the antibody sequence space that remains unknown,” p. 9831, col. 2, para. 2.
Even though the protein sequence of EGFR was known in the art, this would not have translated into knowledge of the genus of antibodies that could possibly engage it. Computational and machine learning approaches for sequence-based prediction of paratope-epitope interactions are accumulating, but “it remains unclear whether antibody-antigen binding is predictable” (Akbar et al., Cell Reports 34, 108856, Mar. 16, 2021 at p. 2, col. 2, para. 2 (PTO 892)). The current state of the art continues to work toward finding an effective and efficient prediction tool for reliably assigning antibody structure based on known target epitopes. See e.g., Lo et al., “Conformational epitope matching and prediction based on protein surface spiral features,” BMC Genomics volume 22, Article number: 116 (2021 (PTO 892)) (disclosing new algorithms that calculate physicochemical properties, such as polarity, charge or the secondary structure of residues within the targeted protein sequences, and then applying quantitative matrix analyses or machine-learning algorithms to predict linear and conformational epitopes).
It is asserted that neither the specification nor the state of art at the time of filing disclosed structural features common to the members of the genus for reliably assigning different antibody structures based on sequence data for 11 antibody clones, which would support the premise that the inventors possessed the full scope of the claimed invention.
Scope of Enablement
10. Claim 32 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the H9 anti-EGFR x anti-CD3 clone for treating a cancer (BxPC-3), does not reasonably provide enablement for treating or preventing an infectious disease or an autoimmune disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
Claim 32 is drawn to administering the antibody-like protein of claim 7 to any subject having any cancer, autoimmune or infectious disease in the absence of a correlation between EGFR expression and the cancer, autoimmune or infectious disease much less where the antibody-like protein is therapeutic (treatment effective) and prophylactic (preventative).
Disclosure in the Specification
The extent of biological testing for an exemplary antibody-like protein was on a single tumor cell line, in vitro, and observed for BxPC-3:
T Cell-Dependent Cellular Cytotoxicity Luciferized BxPC-3 tumor cells (ATCC, CRL-1687) were cultured at 37 ◦C in 5% CO2, in RPMI 1640 media containing 10% fetal bovine serum. A total of 500 tumor cells (20 µL) per well were plated into a 384-well, white, flat-bottom polystyrene TC-treated microplate (Corning 3570) and incubated at 37 ◦C, 5% CO2. After 24 h, 2500 human pan T cells (20 µL) were added to reach an effector-to-target (E–T) ratio of 5:1, and 10 µL of antibody was added at a 5-fold dilution series to reach a final concentration of 0–30 nM. Cells were dispensed using a Multidrop bulk liquid dispenser (BIOTEK). Plates were incubated for an additional 72 h at 37 ◦C, 5% CO2, before luminescence-based cell viability quantification was performed. To quantify the luminescence produced by constitutively expressed firefly luciferase, the Bright-Glo Luciferase Assay System (Promega, E2620, Madison, WI, USA) was used. BrightGlo reagent was added (20 µL per well) at room temperature and luminescence was quantified with a luminescence-detecting plate reader (BMG Labtech). Antibody EC50 was determined by transforming the data in Microsoft Excel and analysis was performed with the GraphPad Prism 6 software “log(agonist) vs. response—variable slope (four parameters).” The resulting EC50 value is reported based on quadruplicate measurements.
The bispcific anti-EGFR x anti-CD3 clone tested for EC50 depleting EGFR+ BxPC3 cells used the H9 clone. Accordingly, the limited disclosure demonstrates a therapeutic effect in mediating cytotoxicity on a single cancer cell line, in vitro.
No where in the specification is there a demonstration of any one of the humanized cetuximab clones shown to have an effect on a cell model correlate to an autoimmune or infectious disease.
No where in the specification is there a demonstration of any one of the humanized cetuximab clones shown to have an effect on a cell model correlate in preventing a cancer, an autoimmune or an infectious disease.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).
The Patent Act requires that patent applicant describes the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek over potentially millions of CH1/CL modified antibodies than the specification teaches how to produce. The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”)
Conclusion
11. No claims are allowed.
12. The following applications are found to be pertinent to the instant claims but are not effective as prior art:
US 20230002488 (SYSTIMMUNE, INC. and BAILI-BIO; priority to 11/5/2020) teaches EGFR H1 VH (SEQ ID NO: 69)/ VL (SEQ ID NO: 71) that corresponds to SEQ ID NOS: 1/3, respectively; EGFR H7 VH (SEQ ID NO: 73)/ VL (SEQ ID NO: 75) that corresponds to SEQ ID NOS: 13/15, respectively; and EGFR H7 VH (SEQ ID NO: 77)/ VL (SEQ ID NO: 79) that corresponds to SEQ ID NOS: 25/27, respectively.
USAN 19/107,585 (PCT US2023/073194; priority to 8/30/2023) teaches the sequence SEQ ID NO: 149.
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 ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643