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
Pursuant to a preliminary amendment filed September 28, 2023 claims 1-47 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group I, claims 1-25, directed to a method for identifying at least one critical quality attribute (CQA) of a protein of interest; and Applicant’s election of Species as follows:
Species (A): wherein the protein of interest is selected from a group consisting of an antibody, a monospecific antibody…and a combination thereof (claim 2);
Species (B): wherein first target molecule and/or the same as the second target molecule is selected from the group consisting of an antibody, an antigen, a receptor, etc. (claim 3);
Species (C): the method of claim 1 further comprising immobilizing sad first molecule to said solid surface prior to step (a) (claim 5);
Species (D): wherein the variants are variants of the protein of interest have modified binding affinity to the target molecule (claim 10);
Species (E): the separation step set forth in claim 17 (Applicant did not elect one of chromatography OR electrophoresis as required) (claim 16);
Species (F): wherein the determination of a CQA is based on the binding of said protein of interest to said first target molecules and/or second target molecules (claim 12); and
Species (G): wherein the protein of interest is selected from a group consisting of an antibody, a monospecific antibody…and a combination thereof (claim 27); and
Species (H): wherein the variants are variants of the protein of interest have modified binding affinity to the target molecule (claim 35), in the reply filed May 26, 2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of invention has been treated as an election without traverse (MPEP
§ 818.03(a)).
Claims 26-47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 11 and 13-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1-10, 12 and 25 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed September 28, 2023 is a CIP of US Patent Application 18229354, filed August 2, 2023; which is a CIP of US Patent Application 17885085, filed August 11, 2022; which is a CIP of US Patent Application 17863303, filed July 12, 2022, which claims the benefit of US Provisional Patent Application 63221436, filed July 13, 2021.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application 63221436, filed July 13, 2021, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for at least; “(c) subjecting a first portion of aid at least two fractions to SPR analysis to characterize the binding of said protein of interest to a second target molecule” in lines 8-10. Therefore, the priority date for the presently claimed invention is July 12, 2022, the filing date of US Patent Application 17/863,303.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 1 of the instant application.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on February 5, 2024; April 2, 2025; August 13, 2025; October 23, 2025; and June 3, 2026 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Specification Objection
This disclosure is objected to because it contains an embedded hyperlink and/or other form of
Browser-executable code (e.g., as-filed Specification, paragraph [0170]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; it is noted that this can be achieved by amending the hyperlink(s) to remove the web-link and/or http:// recitations. See MPEP § 608.01.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-10, 12 and 25 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 1 and 12 are indefinite for the recitation of the term “critical quality attribute” or “CQA” such as recited in claim 1, lines 1 and 13 because the term “critical quality” is a relative term that renders the claim indefinite. The term “critical quality” is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite identity, type, amount and/or quality of an unidentified attribute as compared to some other value that qualifies as a “critical quality” attribute, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention.
Claim 1 is indefinite for the recitation of the term “to characterize the binding of said protein of interest to a second target molecule” such as recited in claim 1, lines 9-10 because claim 1 does not recite the binding of the protein of interest to a second target molecule to a second target molecule, such that it is completely unclear what is being characterized via SPR analysis and, thus, the metes and bounds of the claim cannot be determined.
Claims 2 and 3 are indefinite for the recitation of the term “therapeutic” such as recited in claim 2, line 4 because the term “therapeutic” is a relative term that renders the claim indefinite. The term “therapeutic” is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite activity and/or pharmacological effect as compared to some other protein or target that qualifies a protein/target as a “therapeutic” protein or target. Moreover, it is completely unclear what features of a protein identify it as a “therapeutic protein” such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention.
Claims 2 and 3 are indefinite for the recitation of the term “a combination thereof” such as recited in claim 2, line 5 because claims 2 and 3 depend from instant claim 1, wherein claim 1 does not recite a plurality of first target molecules and/or a plurality of second target molecules, such that the first and/or second target molecules cannot be a combination of the different molecules as recited in the claims. For example, a protein of interest (or a first target molecule) cannot be a combination of an antibody and a fragment of a therapeutic target, or be a bi-specific antibody and a tri-specific antibody and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “contacting a biotinylated first target molecule” such as recited in claim 6, lines 1-2 because claim 6 depends from instant claims 1 and 5, wherein claims 1 and 5 do not recite that the first target molecule is biotinylated and/or the solid surface is a coated solid surface and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “or a variant thereof” such as recited in claim 6, lines 2-3 because it is completely unclear what molecular structures encompass are considered to be variants of avidin and/or streptavidin and, thus, the metes and bounds of the claim cannot be determined.
Claim 8 is indefinite for the recitation of the term “over time” such as recited in claim 8, lines 1-2 because claim 8 depends from instant claims 1 and 7, wherein claims 1 and 7 do not recite any time point and/or passage of time and, thus, the metes and bounds of the claim cannot be determined.
Claim 9 and 10 are indefinite for the recitation of the term “said fractions” such as recited in claim 9, line 1. There is insufficient antecedent basis for the term “said fractions” in the claim because claim 1, lines 6-7 recites the term “at least two fractions”. The Examiner suggests that Applicant amend the claim to recite, for example, “wherein the at least two fractions comprise from 2 to 20 fractions.”
Claim 9 is indefinite for the recitation of the term “a number of said fractions is from 2 to 20…about 9, or about 10” in claim 9, lines 1-2 because a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Instant claim 9 recites a broad range of “from 2 to 20”, while also reciting a narrow range of “or about 4,” which is a narrow range or limitation and, thus, the metes and bounds of the claim cannot be determined.
Claim 10 is indefinite for the recitation of the term “modified binding affinity” such as recited in claim 10, line 2 because claim 10 depends from instant claim 1, wherein claim 1 does not recite a binding affinity for the first target molecule and, thus, the metes and bounds of the claim cannot be determined.
Claim 12 is indefinite for the recitation of the term “determination of a CQA” such as recited in claim 12, line 1 because claim 12 depends from instant claim 1, wherein claim 1 does not recite determining a CQA. Instead, instant claim 1 recites “identifying at least one CQA” and, thus, the metes and bounds of the claim cannot be determined.
Claim 12 is indefinite for the recitation of the term “a CQA” such as recited in claim 12, line 1. There is insufficient antecedent basis for the term “a CQA” in the claim because claim 1, line 1 recites the term “at least one CQA” and, thus, the metes and bounds of the claim cannot be determined.
Claim 12 is indefinite for the recitation of the term “the binding of said protein of interest to…said second target molecule” such as recited in claim 12, lines 1-2 because claim 12 depends from instant claim 1, wherein claim 1 does not recite the binding of a protein of interest to a second target molecule and, thus, the metes and bounds of the claim cannot be determined.
Claim 25 is indefinite for the recitation of the terms “insufficient” such as recited in claim 25, line 1 because the term “insufficient” is a relative terms that renders the claim indefinite. The term “insufficient” is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite amount of first target molecule as compared to some other value that qualifies as an insufficient or sufficient amount to bind all of a protein of interest. Moreover, claim 25 depends from instant claim 1, wherein claim 1 does not recite any amount of the first target molecule. Additionally, the claim is confusing and unclear because claims 1 and 25 do not recite a plurality of proteins of interest, such that it is unclear how much of a target molecule is necessary to bind a single protein of interest and, thus, the metes and bounds of the claim cannot be determined.
Claims 4, 5 and 7 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
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.
Claims 2, 3, 6, 8, 10, 12 and 25 are rejected under 35 U.S.C. 112(d) 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.
Claims 2 and 3 recite (in part): “a fragment thereof, and a combination thereof” such as recited in claim 2, line 5 because claims 2 and 3 depend from instant claim 1, wherein claim 1 does not recite a plurality of first target molecules and/or a plurality of second target molecules, such that the first target molecules and/or second target molecules cannot be a combination of the different molecules as recited (e.g., a bi-specific antibody and a tri-specific antibody). Thus, claims 2 and 3 are improper dependent claims 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 6 recites (in part): “wherein said immobilizing comprises contacting a biotinylated first target molecule to a solid surface that is coated with avidin, streptavidin, or a variant thereof” such as recited in claim 6, lines 1-3 because claims 6 depends from instant claims 1 and 5, such that claims 1 and 5 do not recite that the first target molecule is biotinylated and/or the solid surface is a coated solid surface. Thus, claim 6 is an improper dependent claim 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 8 recites (in part): “wherein a pH of said elution buffer is increased or decreased over time” such as recited in claim 8, lines 1-2 because claim 8 depends from instant claims 1 and 7, wherein claims 1 and 7 do not recite any time point and/or passage of time. Thus, claim 8 is an improper dependent claim 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 10 recites (in part): “wherein said fractions comprise variants of said protein of interest with modified binding affinity to said first target molecule” such as recited in claim 10, lines 1-2 because claim 10 depends from instant claim 1, wherein claim 1 does not recite a binding affinity for the first target molecule. Thus, claim 10 is an improper dependent claim 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 12 recites (in part): “wherein the determination of a CQ/\ is based on the binding of said protein of interest to said first target molecule and/or said second target molecule” such as recited in claim 12, lines 1-2 because claim 12 depends from instant claim 1, wherein claim 1 does not recite the binding of a protein of interest to a second target molecule. Thus, claim 12 is an improper dependent claim 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 25 recites (in part): “wherein an amount of said first target molecule is insufficient to bind all of said protein of interest” such as recited in claim 25, lines 1-2 because claim 25 depends from instant claim 1, wherein claim 1 does not recite any amount of the first target molecule. Thus, claim 25 is an improper dependent claim 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.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 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.
Claims 1-10, 12 and 25 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Schlothauer et al. (hereinafter “Schlothauer”) (US Patent Application Publication 20190127457, published May 2, 2019) as evidenced by GE Healthcare (GE Healthcare, 2011, 1-6); and GE Biosciences (GE Healthcare, 2008, 1-4).
Regarding claim 1, Schlothauer teaches that the term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and/or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts (interpreted as a protein of interest; and variants of the protein of interest, claim 1) (paragraph [0200], lines 1-8). Schlothauer teaches that ALIGN-2, which is a sequence comparison computer program, such that when ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with or against a given amino acid sequence B is calculated as follows: 100 times the fraction X/Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B (interpreted as comparing variants to identify at least one CQA of the protein of interest, claim 1e) (paragraphs [0203], line 20; and [0204]). Schlothauer teaches that using different mutations in the Fc-regions of each heavy chain of a heterodimeric molecule (such as e.g. a bispecific antibody), a heterodimeric molecule can be provided that on one hand has a reduced or even eliminated binding to FcRn, but on the other hand maintains the ability to bind to Staphylococcal protein A, wherein this binding to Staphylococcal protein A can be used to separate the Staphylococcal protein A heterodimeric molecule from homodimeric by-products based on the specific mutations, such that standard protein A affinity chromatography can be used to remove the homodimeric hole-hole by-product as this no longer binds to Staphylococcal protein A (interpreted as contacting a sample including a protein of interest to a first target molecule; and eluting the protein of interest from the solid surface to collect at least two fractions, claim 1a-b) (paragraph [0219], lines 1-10 and 25-27). Schlothauer teaches that dimeric polypeptides can incorporate any of the features, singly or in combination as described in Sections 1-6 including: (1) antibody affinity, wherein Kd is measured using BIACORE surface plasmon resonance assay using a BIACORE-2000 or a BIACORE-3000; (2) chimeric and humanized antibodies; (3) human antibodies; (4) library-derived antibodies; (5) multi-specific antibodies; and (6) antibody variants (paragraph [0301]; [0302], lines 1-3; [0303], Title; [0307], Title; [0311], Title; [0314]; Title; and [0319], Title). Schlothauer teaches that the binding properties of wild-type antibody and the mutants to FcRn were analyzed by surface plasmon resonance (SPR) technology using a BIAcore T100 instrument, wherein this system is well established for the study of molecular interactions; and it allows a continuous real-time monitoring of ligand/analyte bindings and thus the determination of kinetic parameters in various assay settings (interpreting multiple ligands or antibodies on the chip as binding a first target molecule and a second target molecule, claim 1) (paragraph [0597], lines 1-8). Schlothauer teaches that the FcRn receptor was immobilized onto a BIAcore CM5-biosensor chip via amine coupling to a level of 400 Response units (RU); and the assay was carried out at room temperature with PBS, 0.05% Tween 20, pH 6.0 as running and dilution buffer, wherein samples were injected at a flow rate of 50 mL/min (also interpreted as immobilizing FcRn receptor, the first target molecule and second target molecule, to a solid surface of the chip; eluting a sample comprising a protein of interest in buffer; and subjecting a first fraction to SPR, claims 1a-c) (paragraph [0597], lines 15-22). Schlothauer teaches that protein aliquots (50 μg) were deglycosylated by adding N-glycanase plus sodium phosphate buffer (0.1 M, pH 7.1) to obtain a final sample volume of 115 μL; and the mixture was incubated at 37° C. for 18 h, such that afterwards for reduction and denaturing by adding TCEP and guanidine-HCl, the mixture incubated at 37° C, samples were desalted by size exclusion chromatography; and ESI mass spectra (+ve) were recorded on a Q-TOF instrument equipped with a nano ESI source (interpreted as subjecting a portion of the fractions to a mass spectrometry analysis, claim 1d) (paragraph [0596], lines 1-12). Schlothauer teaches the evaluation of SPR-data was performed by comparison of the biological response signal height at 180 sec. after injection and at 300 seconds after injection (interpreted as comparing variants to identify at least one CQA of said protein of interest, claim 1e) (paragraph [0597], last 5 lines). Schlothauer teaches that variant Fc-regions that specifically bind to Staphylococcus protein A and that do not bind to human FcRn, such that these variant Fc regions contain specific amino acid mutations in the CH2- and CH3-domain, wherein these mutations, when used either in the hole chain or the knob chain of a hetero-dimeric Fc-region allow for the purification of the heterodimeric Fe-region, i.e. the separation of a heterodimeric Fc-region from a homodimeric Fc-region (interpreted as comparing variants to identify at least one CQA of the protein of interest, claim 1e) (paragraph [0031]). Schlothauer teaches that antibody variants are provided having a carbohydrate structure that lacks fucose attached (directly or indirectly) to an Fc-region, wherein the amount of fucose in such antibody can be from 1 % to 80%, wherein the amount of fucose is determined by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn 297 (e. g. complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry (interpreted as subjecting a fraction to MS; and comparing variants to identify at least one CQA of said protein of interest, claim 1d-e) (paragraph [0336], lines 1-10). Additionally, Schlothauer teaches that the monospecific and bispecific antibodies were generated by transient transfection with the respective vectors (e.g. encoding the heavy and modified heavy chain, as well as the corresponding light and modified light chain) using the HEK293-F system (interpreted as comprising mutants or variants, claim 1) (paragraph [0624], lines 1-5). Schlothauer teaches that bispecific antibodies were purified from cell culture supernatants by affinity chromatography using MabSelect Sure-Sepharose (for non-IHH-AAA mutants) or KappaSelect-Agarose (for IHH-AAA mutants), hydrophobic interaction chromatography using butyl-Sepharose and Superdex 200 size exclusion chromatography, wherein cell culture supernatants were captured on a MabSelect Sure resin equilibrated (non-IHH-AAA mutations and wild type antibodies) with PBS buffer; and the IHH-AAA mutants were captured on a KappaSelect resin equilibrated with 25 mM Tris, 50 mM NaCl, pH 7.2, washed with equilibration buffer and eluted with 25 mM sodium citrate pH 2.9, wherein the eluted antibody fractions were pooled and neutralized with 2 M Tris, pH 9.0 (interpreting affinity chromatography and resins as contacting a protein of interest to a target molecule on a solid surface, and eluting said protein of interest to collect at least two fractions, claim 1a-b) (paragraph [0625]; and [0626], lines 1-11). Schlothauer teaches that, analogously, the anti-VEGF/ANG2 antibodies, VEGF/ANG2-0012 and VEGF/ANG2-0201 were prepared and purified (paragraph [0629]). Schlothauer teaches that the functional analysis of anti-VEGF/ANG2 bispecific antibodies was assessed by Surface Plasmon Resonance (SPR) using a BIAcore TlO0 or T200 instrument, wherein the SPR allows a continuous real-time monitoring of ligand/analyte binding and, thus, the determination of the association rate constant (ka), dissociation rate constant (kd), and the equilibrium constant (KD) (also interpreted as contacting; eluting; and subjecting to SPR, claims 1a-c) (paragraph [0637], lines 11-4 and 14-17). Schlothauer teaches the characterization of anti-VEGF/ANG2 antibodies with emphasis on the correct assembly, wherein the expected primary structures were confirmed by electrospray ionization mass spectrometry (ESI-MS) of the deglycosylated, and intact or IdeS-digested (IgG-degrading enzyme of S. pyogenes) anti-VEGF/ANG2 antibodies, such that the masses obtained for the IdeS-digested, deglycosylated, or intact, deglycosylated molecules correspond to the predicted masses deduced from the amino acid sequences for the anti-VEGF/ANG2 antibodies consisting of two different light chains LCANG2 and LCLucentis, and two different heavy chains HCANG2 and HCLucentis (interpreted as subjecting a portion of the fractions to mass spectrometry analysis to identify variants of the protein, claim 1d) (paragraph [0652], lines 1-6; and [0653]). Schlothauer teaches that the concentrations of the anti-VEGF/ANG2 antibodies in mice serum and eye lysates were determined with an enzyme linked immunosorbent assay (ELISA) (interpreted as a competitive binding assay) (paragraph [0674).
Regarding claims 2-5, Schlothauer teaches that bispecific antibodies were purified from cell culture supernatants by affinity chromatography using MabSelect Sure-Sepharose (for non-IHH-AAA mutants) or KappaSelect-Agarose (for IHH-AAA mutants), hydrophobic interaction chromatography using butyl-Sepharose and Superdex 200 size exclusion chromatography, wherein cell culture supernatants were captured on a MabSelect Sure resin equilibrated (non-IHH-AAA mutations and wild type antibodies) with PBS buffer; and the IHH-AAA mutants were captured on a KappaSelect resin equilibrated with 25 mM Tris, 50 mM NaCl, pH 7.2, washed with equilibration buffer and eluted with 25 mM sodium citrate pH 2.9, wherein the eluted antibody fractions were pooled and neutralized with 2 M Tris, pH 9.0 (interpret monoclonal antibodies as a protein of interest; interpreting protein A and antibody fragments as encompassing a first target molecule and second target molecule; interpreting MabSelect Sure resin and KappaSelect resin as resins, wherein commercial resins immobilize a first target molecule before the step of contacting, claims 2-5) (paragraph [0625]; and [0626], lines 1-11), wherein it is known that MabSelect Sure is a commercially available agarose-based protein An affinity chromatography resin as evidenced by GE Healthcare (pg. 1, col 1, first full paragraph); and it is known that KappaSelect is a commercially available affinity medium designed for the purification of Fab (kappa) fragments as evidenced by GE Biosciences (pg. 1, col 1, second full paragraph)
Regarding claim 6, Schlothauer teaches that in FcRn chromatography, streptavidin sepharose is added to the biotinylated and dialyzed receptor; and the receptor derivatized sepharose was filled in a XK column (interpreted as biotinylated target molecule; and streptavidin surface, claim 6) (paragraph [0654]).
Regarding claim 7, Schlothauer teaches that FcRn chromatography using an the FcRn affinity column is equilibrated using an equilibration buffer adjusted to a pH 5.5; and eluted with elution buffer adjusted to pH 8.8 (interpreted as an elution buffer; and the elution buffer increases over time, claim 7) (paragraphs [0655]; and [0660])
Regarding claim 8, Schlothauer teaches that after equilibration of the butyl-Sepharose resin with 35 mM sodium acetate, 0.8 M ammonium sulfate, pH 5.0, the antibodies were applied to the resin, washed with equilibration buffer and eluted with a linear gradient to 35 mM sodium acetate pH 5.0. The (monospecific or bispecific) antibody containing fractions were pooled and further purified by size exclusion chromatography using a Superdex 200 26/60 GL column equilibrated with 20 mM histidine, 140 mM NaCl, pH 6.0 (interpreting elution at a linear gradient as the pH increasing or decreasing over time, claim 8) (paragraph [0626], lines 15-24).
Regarding claims 9, 10 and 12, Schlothauer teaches in Figure 8C, FcRn affinity column elution; wild-type anti-IGF-1R antibody (reference), YTE-mutant of anti-IGF-1R antibody, IHH-AAA-mutant of anti-IGF-1R antibody (interpreted as encompassing 2 to 20 fractions; and comprising variants of the protein of interest; CQA is based on the binding of the protein to a first target molecule; and where IHH-AAA-mutant that has a higher abundance and elutes earlier than other fractions, claims 9, 10, 12 and 22) (paragraph [0110], last 4 lines; and Figure 8C). Figure 8C is shown below:
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Regarding claim 25, Schlothauer teaches that it has been found that one mutation, one-sided in one Fc-region polypeptide, is sufficient to weaken the binding significantly, such that the more mutations that are introduced into the Fc-region, the weaker the binding to the FcRn becomes, but one-sided asymmetric mutations are not sufficient to completely inhibit FcRn binding; however, mutations on both sides are necessary to completely inhibit FcRn binding (interpreted as an amount of a first target molecule that is insufficient to bind all of the protein of interest, claim 25) (paragraph [0233]).
Schlothauer meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Double Patenting
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.
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Claims 1-10, 12 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of copending Application No. 18/229,354. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant Application 18/229,354 are directed to a method for identifying at least one critical quality attribute (CQA) of a protein of interest, comprising: (a) contacting a sample including a protein of interest to a target molecule, wherein said protein of interest binds to said target molecule and said target molecule is immobilized to a solid surface; (b) eluting said protein of interest from said solid surface to collect at least two fractions; (c) subjecting said at least two fractions to mass spectrometry (MS) analysis to identify variants of said protein of interest; and (d) comparing said variants to identify at least one CQA of said protein of interest (claim 1); and a method for characterizing binding variants of a protein of interest, comprising: (a) contacting a sample including a protein of interest to a target molecule, wherein said protein of interest binds to said target molecule and said target molecule is immobilized to a solid surface; (b) eluting said protein of interest from said solid surface to collect at least two fractions; (c) subjecting each of said at least two fractions to separation by size or charge to produce a separation profile; and (d) comparing said separation profiles to characterize binding variants of said protein of interest (claim 24).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant Application and the claims of copending Application No. 18/229,354 are directed to identifying at least one CQA of a protein, comprising: contacting, eluting, SPR analysis, MS analysis, and comparing said variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-10, 12 and 25 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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