DETAILED ACTION
Status of Application
Claims 1-48 and 50 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s cancellation of claims 49 and 51-60 as submitted in a communication filed on 07/21/2025 is acknowledged.
Applicant’s election without traverse of Group I, claims 1-48 and 50, drawn to a method for purifying a multispecific protein, as submitted in communication filed on 07/21/2025 is acknowledged.
Claims 49 and 51-60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/21/2025.
Priority
Acknowledgment is made of applicant’s claim for domestic priority under 35 U.S.C. 119 (e) to provisional Application No. 62/931,874 filed on 11/07/2019.
This is the US national application which entered the national stage from Application No. PCT/US2020/058774 filed on 11/04/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/24/2022, 06/18/2024, 09/04/2024, 02/27/2025, and 06/24/2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 5/03/22. These drawings are accepted by the Examiner for examination purposes.
Claim Objections
Claim 46 is objected to due to the recitation of “before and/or after the cation exchange chromatography step, one or more unit operations for purifying the multispecific protein, comprising affinity chromatography, ion exchange chromatography, hydrophobic interaction chromatography column, and/or mixed-mode chromatography column”. To enhance clarity and to be consistent with commonly used claim language, the comma between “protein” and “comprising affinity chromatography” should be removed. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 1-47 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.
Claims 1, 30, 37-38, 41-43, 46-47 (claims 2-29, 31-36, 39-40, 44-45 dependent thereon) are indefinite in the recitation of “multispecific protein” and “bispecific protein” for the following reasons. The terms are unclear in the absence of a statement indicating what are the proteins specific for. A protein, such as an enzyme, can be specific for its substrate. A protein can be specific for the ligand it binds to. A protein can be specific for its function. For examination purposes, it will be assumed that the claims simply refer to a protein. Correction is required
Claim 39 is indefinite in the recitation of “wherein the cation exchange medium is loaded with 15g/L to 30 g/L” for the following reasons: It is unclear as to which is the compound that should be present at the recited concentrations. If the intended compound is the protein being purified, the claim should be amended accordingly.
Claim 40 is indefinite in the recitation of “wherein the cation exchange medium is loaded with 25g/L to 40 g/L” for the following reasons: It is unclear as to which is the compound that should be present at the recited concentrations. If the intended compound is the protein being purified, the claim should be amended accordingly
Claim 45 is indefinite in the recitation of “a purification method that includes a unit operation comprising cation exchange chromatography preformed according to the method of claim 1” for the following reasons. As written, it is unclear if the purification process simply requires a cation exchange chromatography step or if it requires the loading, washing and elution steps of the method of claim 1 as well as the same protein purified by the method of claim 1. For examination purposes, it will be assumed that claim 45 is a duplicate of claim 1. Correction is required.
Claim Rejections - 35 USC § 102 (AIA )
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.
Claims 1-3,17,30-34, 44-45, 47, and 50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yosuke et al. (JP-2016183113 Published 10/20/2016) as evidenced by the Fisher Scientific Catalog (product No. 50-851-205, 2026) and as evidenced by Brinkmann et. al (mAbs, VOL 9, pages 182-212, 2017). The examiner will use the English translation provided when referring to specific teachings relevant to the instant claims.
Claims 1-3, 45, 47, and 50 as interpreted are directed in part to a method for purifying a protein onto a cation exchange chromatography medium, wherein said method comprises (a) washing the cation exchange medium with at least one wash buffer comprising 100 - 147 mM sodium chloride, (b) eluting the multispecific protein from the cation exchange chromatography resin, wherein at least one wash buffer comprises 100-125mM, 100-105 mM of sodium chloride, and (c) wherein the multispecific protein is a bispecific protein. Claim 17 as interpreted are directed to the process of claim 1, as described above, wherein the cation exchange medium is washed with at least two buffers. Claims 30-34 as interpreted are directed to the process of claim 1, as described above, wherein the protein is eluted from the cation exchange medium by a salt gradient that is a linear or step gradient with an elution buffer that comprises 0-1 M NaCL or 70-500 mM NaCl. Claim 44 as interpreted is directed to the process of claim 1, as described above, wherein at least one product-impurity is a homodimer, high molecular weight species, half antibody, aggregate, low molecular weight species, antibody fragment, or a light chain mis-assembly.
Yosuke et al. teaches a method for purifying an Fc binding protein using a cation chromatography resin, wherein the method requires at least one wash with a buffer comprises 100mM of sodium chloride (page 5, paragraph 0018, line 12). Yosuke et al. also teaches using two washes with two buffers (page 5, paragraph 0018, line 5). Yosuke et al. teaches elution with a salt gradient that is step gradient (paragraph 0011, page 4, line 10) with an elution buffer having an NaCl concentration of 250 mM (page 5, paragraph 0019, line 1). Youske et al. teaches a TOYOPEARL CM-650M cation exchange medium (Page 5, paragraph 0017, line 3) which is a resin as evidenced by the Fisher Scientific catalog product No. 50-851-205. Yosuke et al. teaches a method for purifying fc-binding proteins (Page 3, paragraph 0001, line 1) which can be a bispecific protein as evidenced by Brinkmann et. al (page 183, right column, first paragraph). Youske et al. teaches a method for purifying an Fc binding protein using a cation chromatography resin, wherein the sample comes from an E.coli supernatant, which would comprise intracellular components such as amino acids, saccharides, and metabolites that are considered low molecular weight species (page 10, paragraph 0029, line 21). Therefore, the teachings of Yosuke et al. anticipate the instant claims as written/interpreted.
Claim Rejections - 35 USC § 103 (AIA )
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.
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.
Claims 4-6, 18-20, 29, 35-43, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Yosuke et al. (JP2016183113A published 10/20/2016) as evidenced by the Fisher Catalog (product No. 50-851-205, 2026).
The teachings of Yosuke et al. have been described above. Yosuke et al. teach that the wash buffer comprises less than 150 mM of sodium chloride (page 4, paragraph 0011, line 7). Claims 4-6 are directed in part to the process of claim 1 wherein at least one wash buffer comprises 105-147mM, 105-125mM, or 125-147mM of sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use wash buffers having the recited NaCl concentrations. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150 mM. Any concentration below 150 mM is clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at arriving to these concentrations because all that is required is adjusting the amount of NaCl used in the preparation of the wash buffers. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach using two wash buffers to remove contaminants (page 5, paragraph 0018). Claim 18 is directed in part to the process of claim 1 wherein the cation exchange buffer is washed with at least three wash buffers. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to wash the cation exchange medium with three wash buffers. A person of ordinary skill in the art is motivated to wash with three wash buffers for the benefit of removing additional contaminants from the resin. One of ordinary skill in the art has a reasonable expectation of success at using three buffers because all that is required is adding an additional wash step to the method of Yosuke et al. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach using two wash buffers to remove contaminants (page 5, paragraph 0018) and teach that at least one wash buffer comprises 150mM or less of sodium chloride (page 4, paragraph 0011, line 7). Claim 19 is directed in part to the process of claim 18 wherein the cation exchange buffer is washed with at least two wash buffers, at least one of the wash buffers comprising 0-147 mM sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use two wash buffers having a concentration within the recited NaCl concentration range. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150 mM. Any concentration below 150 mM and the use of two buffers are clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at arriving to using two wash buffers with this concentration range because all that is required is adjusting the amount of NaCl used in the preparation of the wash buffers, along with changing the amount of wash buffers used. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 20 is directed in part to the process of claim 19 wherein the cation exchange buffer is washed with at least two wash buffers, at least one of the wash buffers comprising 0-70 mM sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use two wash buffers having a concentration within the recited NaCl concentration range. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150mM. Any concentration below 150 mM and the use of two buffers are clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at arriving to using two wash buffers with this concentration range because all that is required is adjusting the amount of NaCl used in the preparation of the wash buffers. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 29 is directed in part to the process of claim 1 wherein the cation exchange medium is washed with 2.5 mM/CV of a wash buffer comprising 147 mM sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use two wash buffers having a concentration within the recited NaCl concentration range. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150mM. Any concentration below 150 mM and the use of two buffers are clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at arriving to using two wash buffers with this concentration range because all that is required is adjusting the amount of NaCl used in the preparation of the wash buffers. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach using a method for eluting a protein with sodium chloride (page 5, paragraph 0019, line 1). Claim 35 is directed in part to the process of claim 33 wherein at least one elution buffer comprises 125mM of sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use an elution buffer that comprises 125 mM of sodium chloride. A person of ordinary skill in the art is motivated to use this concentration because the choice of NaCl concentration would depend on the nature of the protein to be purified. Different proteins would elute at different NaCl concentrations depending on their charge. One of ordinary skill in the art has a reasonable expectation of success at arriving to this concentration because all that is required is adjusting the amount of NaCl used in the preparation of the elution buffer. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach that the wash buffer comprises less than 150 mM of sodium chloride (page 4, paragraph 0011, line 7) and teach a method for eluting a protein with sodium chloride (page 5, paragraph 0019, line 1). Claim 36 is directed in part to the process of claim 1 wherein at least one wash buffer and one elution buffer comprises 125mM of sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a wash buffer having a concentration within the recited NaCl concentration range and to use an elution buffer that comprises 125 mM of sodium chloride. A person of ordinary skill in the art is motivated to use these wash buffer concentrations because they are also lower than 150mM. Any wash buffer concentration below 150 mM is clearly suggested by Yosuke et al. A person of ordinary skill in the art is motivated to use the recited elution concentration because the choice of NaCl concentration would depend on the nature of the protein to be purified. Different proteins would elute at different NaCl concentrations depending on their charge. One of ordinary skill in the art has a reasonable expectation of success at arriving to using one wash buffer and one elution buffer comprising 125mM NaCl. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach the purification method of fc-binding protein wherein the protein is loaded into the chromatography column (page 4, paragraph 0014, line 1). Claims 37-40 are directed in part to the process of claim 1 wherein the cation exchange medium is loaded with 10 g/L, 10 g/L to 40g/L, 15g/L to 30g/L, and 25g/L to 40g/L of the protein. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to load the column with 10 g/L, 10 g/L to 40g/L, 15g/L to 30g/L, or 25g/L of the protein to be purified. A person of ordinary skill in the art is motivated to use any of the recited concentrations because the choice of protein concentration would depend on how much purified protein is desired, the binding capacity of the resin, and the protein concentration obtained from the process that generates the protein. One of ordinary skill in the art has a reasonable expectation of success at using different protein concentrations because all that is required is adjusting the amount of resin used. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach the purification method of fc-binding proteins with the use of a salt gradient (page 5, paragraph 0018). Claim 41 is directed in part to the process of claim 1 wherein the cation exchange medium is loaded with 10g/L of the multispecific protein, washed with a wash buffer comprising 105 mM sodium chloride and eluted in a salt gradient at 8 mM/CV. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a cation exchange medium with 10g/L of the multispecific protein, to wash the column medium with 105 mM sodium chloride and to elute in a salt gradient at 8 mM/CV. A person of ordinary skill in the art is motivated to use the recited protein concentrations because the choice of protein concentration would depend on how much purified protein is desired, the binding capacity of the resin, and the protein concentration obtained from the process that generates the protein. A person of ordinary skill in the art is motivated to use a salt gradient at 8 mM/CV because the choice of salt gradient would depend on the nature of the protein to be purified, the level of impurities in the sample loaded to the column, the type of resin used and the degree of purity desired. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150 mM. Any concentration below 150 mM is clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at using the recited protein concentration, desired gradient, and desired NaCl concentration because all that is required is adjusting the amount of resin used, the NaCl concentration of the elution buffer and the flow rate, and the amount of NaCl used in the preparation of the elution buffer. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach that the wash buffer comprises less than 150 mM of sodium chloride (page 4, paragraph 0011, line 7) and teach the purification method of fc-binding protein wherein the protein is loaded into the chromatography column (page 4, paragraph 0014, line 1). Claim 42 is directed in part to the process of claim 1 wherein the cation exchange medium is loaded with 15g/L to 30g/L of the multispecific protein, washed with a wash buffer comprising 147 mM sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to load the column with 15g/L to 30g/L of the protein to be purified. A person of ordinary skill in the art is motivated to use the recited concentrations because the choice of protein concentration would depend on how much purified protein is desired, the binding capacity of the resin, and the protein concentration obtained from the process that generates the protein. One of ordinary skill in the art has a reasonable expectation of success at using different protein concentrations because all that is required is adjusting the amount of resin used. A person of ordinary skill in the art is motivated to use the recited concentration because it is lower than 150 mM. Any concentration below 150 mM and the use of two buffers are clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at using different protein concentrations with two wash buffers comprising the desired amount of NaCl, because all that is required is adjusting the amount of resin used and the amount of NaCl used in the preparation of the wash buffers. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach that the wash buffer comprises less than 150 mM of sodium chloride (page 4, paragraph 0011, line 7), an elution buffer that comprises 250mM of sodium chloride (page 4, paragraph 0011, line 10), and teach the purification method of fc-binding protein wherein the protein is loaded into the chromatography column (page 4, paragraph 0014, line 1). Claim 43 is directed in part to the process of claim 1 wherein the cation exchange medium is loaded with 25g/L to 40g/L of the multispecific protein, washed with a wash buffer and an elution buffer comprising 125 mM sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to load the column with 25g/L to 40g/L of the protein to be purified. A person of ordinary skill in the art is motivated to use the recited concentrations because the choice of protein concentration would depend on how much purified protein is desired, the binding capacity of the resin, and the protein concentration obtained from the process that generates the protein. A person of ordinary skill in the art is motivated to use the recited concentration because it so lower than 150 mM. Any concentration below 150 mM are clearly suggested by Yosuke et al. One of ordinary skill in the art has a reasonable expectation of success at arriving to using different protein concentrations and wash buffers with the recited concentration, because all that is required is adjusting the amount of resin used and NaCl used in the preparation of the wash buffers. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 7-16, 21-28, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Yosuke et al. (JP2016183113A published 10/20/2016) in view of Kang et al. (WO/2018/190677 filed on 4/13/2018).
The teachings of Yosuke et al. have been discussed above. Yosuke et. al teach a purification process for fc-binding proteins using wash buffers compromising NaCl (page 4, paragraph 0011, line 7), but do not teach a wash buffer comprising acetate. Kang et al. teach purifying antibodies using buffers with other salts including, but not limited to, NaCl (page 6, paragraph 64) and different chromatography steps (page 9, paragraph 94, line 2). Kang et al. teach a protein purification process with the use of acetate wash buffers to wash the column medium (page 6, paragraphs 57-63). Kang et al. teach a protein purification process with the use of acetate wash buffers to wash the column medium, pH 4.5-5.2 (page 9, paragraph 93, Table 1). Claims 7-11 are directed in part to the process of claim 1 having at least one wash buffer that comprises acetate, wherein the acetate pH is 5.0 ±0.05% to pH 5.0 ±0.1%, pH 4.91-5.1, 4.9, 5.0, or 5.1 and the concentration of acetate is 100mM . It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use wash buffers comprising acetate with the recited pHs and concentration. A person of ordinary skill in the art is motivated to modify the method in Yosuke et al. and incorporate acetate to widen the range of impurities removed from the column medium beyond what could be removed with sodium chloride. One of ordinary skill in the art has a reasonable expectation of success at arriving to using acetate at the recited pHs and concentration in cation exchange chromatography because all that is required is adding another column medium preparation step to the method used in Yosuke et. al to remove different impurities. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach that the wash buffer comprises less than 150 mM of sodium chloride (page 4, paragraph 0011, line 7) but do not teach a wash buffer comprising acetate. Kang et al. teach a protein purification process with the use of acetate wash buffers to remove impurities from the column medium (page 9, paragraph 93, Table 1). Claims 12-16 are directed in part to the process of claim 1 wherein at least one wash buffer comprises acetate, and 100-125mM, 100-105mM, 105-147mM, 105-125mM, or 125-147mM of NaCl. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use wash buffers comprising acetate with the recited NaCl concentrations. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150 mM. Any concentration below 150 mM is clearly suggested by Yosuke et al. A person of ordinary skill in the art is motivated to modify the method in Yosuke et al. and incorporate acetate to widen the range of impurities removed from the column medium beyond what could be removed with sodium chloride alone. One of ordinary skill in the art has a reasonable expectation of success at arriving to these NaCl concentrations with the addition of acetate because all that is required is adjusting the amount of NaCl used in the preparation of the wash buffers in addition to acetate to remove different impurities. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach that the wash buffer comprises less than 150 mM of sodium chloride (page 4, paragraph 0011, line 7) and teaches two wash buffers to remove contaminants (page 5, paragraph 0018 ), but do not teach a wash buffer comprising acetate. Kang et al. teach a protein purification process with the use of acetate wash buffers to wash the column medium (page 9, paragraph 93, Table 1). Claims 21-28 are directed in part to the process of claim 1 wherein the cation exchange medium is washed with at least two wash buffers, at least one wash buffer comprising acetate, 0 mM sodium chloride, followed by a wash buffer comprising acetate and different concentrations of sodium chloride. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the recited number of wash buffers having the recited NaCl concentrations with acetate. A person of ordinary skill in the art is motivated to use these concentrations because they are also lower than 150 mM. Any concentration below 150 mM is clearly suggested by Yosuke et al. A person of ordinary skill in the art is motivated to modify the method in Yosuke et al. and incorporate acetate to widen the range of impurities removed from the column medium beyond what could be removed with sodium chloride alone. One of ordinary skill in the art has a reasonable expectation of success at arriving to these NaCl concentrations with the addition of acetate because all that is required is adjusting the amount of NaCl used in the preparation of the wash buffers in addition to acetate to remove different impurities. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Yosuke et al. teach a method of purification of fc-binding proteins (page 4, paragraph 0014, line 1), but do not teach using an addition chromatography method. Kang et al. teach the use of affinity chromatography before cation exchange chromatography to obtain high purity antibody fragments (page 9, paragraph 94, line 2). Claim 46 is directed in part to the process of claim 1 further comprising, before and/or after the cation exchange chromatography step, one or more unit operations for purifying the multispecific protein, comprising affinity chromatography, ion exchange chromatography, hydrophobic interaction chromatography column, and/or mixed-mode chromatography column. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the additional affinity chromatography in Kang et al. before the cation exchange method in Yosuke et al. It is suggested by Kang et al. to use affinity chromatography before cation exchange chromatography. A person of ordinary skill in the art is motivated to use another form of chromatography for the benefit of increasing the purity of the protein. One of ordinary skill in the art has a reasonable expectation of success at using another form of chromatography because all that is required is adding an additional chromatography step to the method of Yosuke et al. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Yosuke et al. (JP2016183113A published 10/20/2016) in view of Spiess et al. (The Journal of Biological Chemistry, Vol. 288, pages 26593-26593, 2013, published on 9/13/2013).
The teachings of Yosuke et al. have been described above. Yosuke et al. teach the purification method of fc-binding protein wherein the protein is loaded into the chromatography column (page 4, paragraph 0014, line 1). Spiess et al. teach a bispecific antibody being purified by a cation exchange chromatography step (page 26585, left column, full paragraph 4). Claim 48 is directed in part to the process of claim 1 wherein the multispecific protein is a bispecific antibody. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to load the column with a bispecific antibody to be purified. A person of ordinary skill in the art is motivated to use a bispecific antibody to be purified because cation exchange chromatography has been used to purify bispecific antibodies. One of skill in the art has a reasonable expectation of success at using the method of Yosuke et al. to purify bispecific antibodies because the method of Yosuke et al. also teaches purification of another binding protein with cation exchange chromatography. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is in condition for allowance
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/SYNPHANE L SHELTON/Examiner, Art Unit 1652
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652