DETAILED ACTION
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 .
Status of Application, Amendments and/or Claims
Applicant’s election without traverse of Group I (claims 1-46, 48-53) in the reply filed on 15 October 2025 is acknowledged. Claims 47, 54-57 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 15 October 2025. Claims 1-46, 48-53 are under examination.
Information Disclosure Statement
The information disclosure statement(s)(IDS) (filed 8/24/22, 9/10/24, 8/28/25 and 10/15/25) were received. They have been placed in the application file and the information referred to therein has been considered as to the merits.
It is noted that some of the references fail to comply with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. MPEP 609.05 [R-3] states that information disclosure statements will be reviewed for compliance with the requirements of 37 CFR 1.97 and 37 CFR 1.98 as discussed in MPEP 609.04(a) and MPEP 609.04(b). The references will be lined through and not considered by the Examiner.
References: The references should include the name of the author, title of the article, name of the item (i.e. book, magazine, Journal, symposium, catalog, etc.), the volume-issue number, the pages, and date.
The following reference is not considered by the Examiner for the following reasons:
(1) The JP 2016/18113 reference (submitted 8/24/2022) is not considered by the Examiner because it is in a language other than English and does not have an English abstract. The citation is also missing the name of patentee or applicant of the document.
Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
DUPLICATE CLAIM WARNING
Applicant is advised that should claims 8 and 20 be found allowable, claims 12 and 24 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k).
(1) In the instant case, claim 8 recites, “the method according to claim 1, wherein the load buffer comprises acetate. Claim 8 depends from claim 1, which states that the load buffer comprises 94-105 mM sodium chloride.
Claim 12 recites, “the method according to claim 1, wherein the load buffer comprises acetate, 94-105 sodium chloride”.
Therefore, claims 8 and 12 are both drawn to load buffers comprising acetate and 94 mM-105 mM sodium chloride.
(2) In the instant case, claim 20 recites, “the method of claim 1, wherein at least one wash buffer comprises acetate. Claim 20 depends from claim 1, which states that the wash buffer comprises 94-105 mM sodium chloride.
Claim 24 recites, “the method according to claim 1, wherein at least one wash buffer comprises acetate, 94 mM-105 mM sodium chloride”.
Therefore, claims 20 and 24 are both drawn to wash buffers comprising acetate and 94 mM-105 mM sodium chloride.
If the claims are not of similar scope, Applicant is asked to specifically point in the specification, the patentable distinction between the claims.
Claim Objections
Claims 1, 29, 49, 50 and 52 are objected to because of the following informalities:
(1) For claims 1 and 49:
In line 5, the word “comprises” should recite “comprising”.
In line 5, the word “chromatography” should be inserted after “exchange” for consistency with lines 3 and 9.
(2) Claim 29 needs a space between “105” and “mM”.
(3) For claim 50, both recitations of the term “impurity” should be amended to recite “impurities” (i.e., “wherein the low pI impurity impurities are product-related impurities”). This provides consistency with claim 49
(4) For claim 52:
In line 4, the word “chromatography” should be inserted after “exchange” for consistency with lines 3 and 6.
In line 7, the word “loading” should recite “load” for consistency with line 4.
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.
Claims 27 and 49-53 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.
(1) Claims 27 and 53 are indefinite for the following reasons. The instant claims recite that the “additional wash buffer” or “second wash buffer” comprises “0-26 mM sodium chloride”. It is unclear what the “additional wash buffer” or “second wash buffer” comprises if there is 0 mM sodium chloride. The metes and bounds of these claims cannot be determined.
(2) Claim 49 is indefinite because it has insufficient antecedent basis for certain limitations.
Improper antecedent basis in line 5 of “loading the composition”. It is suggested to amend the claim to recite “loading a composition”.
Improper antecedent basis in line 7 of “the column”.
Improper antecedent basis in line 8 of “the multispecific protein”. It is also not clear if the multispecific protein is in the composition loaded onto the cation exchange chromatography medium.
Claims 50-51 are included in this rejection insofar as they depend from claim 49 and do not solve the issue above.
(3) Claim 52 is indefinite because it has insufficient antecedent basis for certain limitations.
Improper antecedent basis in line 4 of “loading the composition”. It is suggested to amend the claim to recite “loading a composition”.
Improper antecedent basis in line 5 of “the column”.
Improper antecedent basis in line 6 of “the multispecific protein”. It is also not clear if the multispecific protein is in the composition loaded onto the cation exchange chromatography medium.
Claim 53 is included in this rejection insofar as it depends from claim 52 and does not solve the issue above.
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 13, 25, 26 and 29 are 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.
(1) Claim 13 recites, “the method according to claim 1, wherein at least one wash buffer comprises 94-105 mM sodium chloride”. Claim 13 depends from claim 1, which recites, “at least one wash buffer comprising 94-105 mM sodium chloride”.
Claim 13 fails to further limit claim 1, because claim 1 already states that the wash buffer comprises 94-105 mM sodium chloride.
(2) Claim 25 recites, “the method according to claim 1, wherein the method comprises at least one additional wash buffer”. Claim 25 fails to further limit claim 1 because claim 1 recites “at least one wash buffer”. The limitation “at least one” encompasses more than one wash buffer (i.e. additional wash buffers).
(3) Claim 26 recites, “the method according to claim 25, wherein at least one additional wash buffer is a second wash buffer”. Claim 26 fails to further limit claim 25 because it does not teach how a “second wash buffer” is different from an “additional wash buffer” (as recited in claim 25).
(4) Claim 29 recites, “the method according to claim 1, wherein at least one equilibration buffer comprises 94-105 mM sodium chloride”. Claim 29 depends from claim 1, which recites “equilibrating a cation exchange chromatography medium with an equilibration buffer comprising 94-105 mM sodium chloride”.
Claim 29 fails to further limit claim 1, because claim 1 already states that the equilibration buffer comprises 94-105 mM sodium chloride.
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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(1) Claims 1, 3, 13, 15, 25, 26, 29, 31, 45, 48, 49 and 52 are rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Bergquist et al. (US 2010/0151518; published June 17, 2010).
Bergquist et al. teach a method for producing a replicase EF-Ts, EF-Tu and .beta. polypeptide subunits, wherein the EF-Ts and EF-Tu subunits are operably linked to a first promoter and the .beta. subunit is operably linked to a second promoter (abstract and para 0008)(i.e. multispecific and bispecific proteins; applies to claims 1 and 45). Bergquist et al. teach using cation resin exchange columns to purify the multispecific protein (paras 0018, 0027, 0069)(applies to claims 1 and 48). Bergquist et al. teach a method comprising diluting proteins with a buffer comprising 100 mM NaCl, applying the proteins to a cation exchange column equilibrated with buffer B comprising 100 mM NaCl, extensively washing with the same buffer and eluting the protein (para 0088)(applies to claims 1, 3, 13, 15, 25, 26, 29, 31, 49 and 52).
(2) Claims 1-3, 8-15, 20-31, 36, 39-44, 48-53 are rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Lee et al. (US 2016/0264618; published Sep 15, 2016).
Lee et al. teach a method for separating antibody isoforms using cation exchange chromatography comprising loading an antibody-containing sample onto a cation exchange chromatography column equilibrated with an equilibration buffer; washing the column with a washing buffer and recovering a target antibody from the column using an elution buffer (abstract and paras 0009-0026). Lee et al. teach various cation resins (para 0020)(applies to claim 48). Lee et al. teach that as used herein, the term “antibody” or “immunoglobulin” refers to a protein consisting of one or more polypeptides substantially encoded by antibody genes. The recognized antibody genes include the different constant region genes as well as the myriad antibody variable region genes (para 0052)(i.e., multispecific antibody; applies to claim 1).
Lee et al. teach equilibrium buffers. Lee et al. teach the equilibrium buffer has a salt concentration of 10-300 mM or maybe 100 mM or less. Lee et al. teach the equilibrium buffer can comprise any one selected from the group consisting of sodium acetate and sodium chloride (paras 0010, 0014, 0024, 0033, 0035)(applies to claims 1, 29, 30, 31, 36, 39, 52). Lee et al. teach wash buffers. Lee et al. teach the wash buffer has a salt concentration of 10-300 mM or maybe 100 mM or less. Lee et al. teach the wash buffer can comprise any one selected from the group consisting of sodium acetate and sodium chloride. Lee et al. teach more than one wash (paras 0011, 0025, 0032, 0079 and 0095)(applies to claims 1, 13, 14, 15, 20, 23-28, 52 and 53). Lee et al. teach the pH of the wash buffer is between 5.0-8.0 (para 0027)(applies to claims 21 and 22). Lee et al. teach that the pH and salt concentration conditions of the washing buffer are applied to the loading conditions of the cation exchange chromatography column; antibody isoforms can be separated in the same or similar manner (para 0045)(applies to claims 1-3, 8-12 and 52). Lee et al. teach wherein the multispecific protein is eluted from the cation exchange resin by a linear salt gradient (paras 0048-0051)(applies to claims 42-44). Lee et al. teach antibody isoforms, isoelectric points (pI) and removing impurities such as protein aggregates and protein fragments (para 0053, 0056, 0057 and claims)(applies to claims 49-51). Lee et al. teach wherein the antibody composition is loaded up to 20 g/L (para 0074)(applies to claims 40 and 41).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(1) Claims 1, 3, 13-18, 20-26, 29, 31, 45, 46, 48, 49 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Bergquist et al. (US 2010/0151518; published June 17, 2010) in view of Wang et al. (US 2019/0046956; published Feb 14, 2019, priority date June 21, 2017).
Bergquist et al. teach a method for producing a replicase EF-Ts, EF-Tu and .beta. polypeptide subunits, wherein the EF-Ts and EF-Tu subunits are operably linked to a first promoter and the .beta. subunit is operably linked to a second promoter (abstract and para 0008)(i.e. multispecific and bispecific; applies to claims 1 and 45). Bergquist et al. teach using cation resin exchange columns to purify the multispecific protein (paras 0018, 0027, 0069)(applies to claims 1 and 48). Bergquist et al. teach a method comprising diluting proteins with a buffer comprising 100 mM NaCl, applying the proteins to a cation exchange column equilibrated with buffer B comprising 100 mM NaCl, extensively washing with the same buffer and eluting the protein (para 0088)(applies to claims 1, 3, 13, 15, 25, 26, 29, 31, 49 and 52).
Bergquist et al. do not teach washing buffers comprising less than 100 mM NaCl.
Wang et al. teach wash buffers comprising a surfactant for use in cation exchange chromatography to purify proteins of interest from protein aggregates and to remove and/or inactivate viruses. Wang et al. teach when used during cation exchange chromatography for the purification of a protein of interest, such as an antibody, the wash buffer significantly improves viral clearance from the preparation, while also reducing the levels of host cell proteins and protein aggregates (abstract and paras 0003, 0011-0012, 0014 and 0015). Wang et al. teach various cation resin exchange columns (para 0022)(applies to claim 48). Wang et al. teach the term “antibody” encompasses bispecific and multispecific antibodies (paras 0068 and 0069)(applies to claim 46).
Wang et al. teach that the wash solution may be any such solution described or exemplified herein, including those wash solutions described in the following sections. Wang et al. teach that the intermediate wash buffer may be any aqueous cation exchange (CEX) wash buffer, such as a CEX equilibration buffer, or any of the CEX wash solutions described herein, with the proviso that it does not contain a surfactant. In one embodiment, the intermediate wash buffer is of the same composition as any one of the CEX wash solutions described herein, without the surfactant (para 0015). Wang et al. teach more than one wash (paras 0023 and 0033). Wang et al. teach the pH of the wash buffers are about 5.0 to 7.0 or of about 5.5 or about 6.3 (paras 0049 and 0140)(applies to claims 20-22). Wang et al. teach that acetate can be added to the wash buffer, such as or about 100 mM sodium acetate (paras 0047 and 0144)(applies to claims 20, 21, 22, 23). Wang et al. teach that the wash buffer can comprise about 90 mM or about 95 or about 100 mM NaCl (paras 0115 and 0142)(applies to claims 13, 14, 15, 24).
Wang et al. do not specifically teach that the wash buffer can comprise 94 mM, 96 mM or 98 mM NaCl. However, Wang clearly teaches that the wash buffer can comprise about 90 mM or about 95 or about 100 mM NaCl. Modification such as adjusting the concentrations of buffers are deemed a matter of judicious selection and routine optimization, absence evidence of unexpected results (applies to claims 16-18).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a method of using cation exchange chromatography to isolate/purify multispecific proteins, wherein the wash buffer comprises 100 mM NaCl, as taught by Bergquist et al. by using washing buffers that comprises about 90 mM or about 95 or about 100 mM NaCl, as taught by Wang et al. One of ordinary skill in the art at the time the invention was made would have been motivated to make such modifications and expect success for the following reasons. Bergquist et al. teach 100 mM NaCl and Wang et al. teach a range about 90 mM or about 95 or about 100 mM NaCl. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955)(MPEP 2144.05). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (see also MPEP 2144.04).
2. Claims 1-36, 39-44, 48-53 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2016/0264618; published Sep 15, 2016).
Lee et al. teach a method for separating antibody isoforms using cation exchange chromatography comprising loading an antibody-containing sample onto a cation exchange chromatography column equilibrated with an equilibration buffer; washing the column with a washing buffer and recovering a target antibody from the column using an elution buffer (abstract and paras 0009-0026). Lee et al. teach various cation resins (para 0020)(applies to claim 48). Lee et al. teach that as used herein, the term “antibody” or “immunoglobulin” refers to a protein consisting of one or more polypeptides substantially encoded by antibody genes. The recognized antibody genes include the different constant region genes as well as the myriad antibody variable region genes (para 0052)(i.e.,, multispecific; applies to claim 1).
Lee et al. teach equilibrium buffers. Lee et al. teach the equilibrium buffer has a salt concentration of 10-300 mM or maybe 100 mM or less. Lee et al. teach the equilibrium buffer can comprise any one selected from the group consisting of sodium acetate and sodium chloride (paras 0010, 0014, 0024, 0033, 0035)(applies to claims 1, 29, 30, 31, 36, 39, 52). Lee et al. teach wash buffers. Lee et al. teach the wash buffer has a salt concentration of 10-300 mM or maybe 100 mM or less. Lee et al. teach the wash buffer can comprise any one selected from the group consisting of sodium acetate and sodium chloride. Lee et al. teach more than one wash (paras 0011, 0025, 0032, 0079 and 0095)(applies to claims 1, 13, 14, 15, 20, 23-29, 52 and 53). Lee et al. teach the pH of the wash buffer is between 5.0-8.0 (para 0027)(applies to claims 21 and 22). Lee et al. teach that the pH and salt concentration conditions of the washing buffer are applied to the loading conditions of the cation exchange chromatography column; antibody isoforms can be separated in the same or similar manner (para 0045)(applies to claims 1-3, 8-12 and 52). Lee et al. teach wherein the multispecific protein is eluted from the cation exchange resin by a linear salt gradient (paras 0048-0051)(applies to claims 42-44). Lee et al. teach antibody isoforms, isoelectric points (pI) and removing impurities such as protein aggregates and protein fragments (para 0053, 0056, 0057 and claims)(applies to claims 49-51). Lee et al. teach wherein the antibody composition is loaded up to 20 g/L (para 0074)(applies to claims 40 and 41).
Lee et al. do not specifically teach that the equilibrium buffer, load buffer and wash buffer comprises 94 mM, 96 mM, 98 mM NaCl or 105 mM NaCl.
However, it would have been obvious for one of ordinary skill in the art before the effective filling date to modify a method of using cation exchange chromatography to isolate/purify multispecific antibodies, wherein the equilibrium buffer, load buffer and wash buffer comprises 94 mM, 96 mM, 98 mM NaCl or 105 mM NaCl. One of ordinary skill in the art at the time the invention was made would have been motivated to make such modifications and expect success for the following reasons. Lee clearly teaches that the equilibrium buffer, load buffer and wash buffer can comprise 10-300 mM or maybe 100 mM or less NaCl. Modification such as adjusting the concentrations of buffers are deemed a matter of judicious selection and routine optimization, absence evidence of unexpected results. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955)(MPEP 2144.05). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (see also MPEP 2144.04) (applies to claims 4-7, 16-19, 32-35).
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 8-15, 20-31, 36, 39-46, 48, 52 and 53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-15, 17-19, 20, 21, 23, 24, 30-32, 37-40, 47, 48, 50 and 53 of copending Application No. 17/773,892 in view of Lee et al. (US 2016/0264618; published Sep 15, 2016).
The instant claims are drawn to a method of purifying a multispecific protein from a composition comprising the multispecific protein and at least one product-related impurity, the method comprising equilibrating a cation exchange chromatography medium with an equilibration buffer comprising 94-105 mM sodium chloride; loading the composition on to the cation exchange medium in a load buffer comprises 94-105 mM sodium chloride; washing the column with at least one wash buffer comprising 94-105 mM sodium chloride; and eluting the multispecific protein from the cation exchange chromatography medium. The claims are further drawn wherein the equilibrium buffer, load buffer and/or wash buffer comprises 100 mM acetate. The claims are further drawn to additional wash buffers or second wash buffers comprising 0-26 mM sodium chloride. The claims are further drawn to wherein the load buffer and the wash buffer have a pH between 4.9-5.1. The claims are further drawn to wherein the composition is loaded at 10-27 g/L. The claims are further drawn to wherein the multispecific protein is eluded by a linear gradient or a salt gradient. The claims are further drawn to wherein the multispecific protein is a bispecific antibody. The claims are further drawn to wherein the cation exchange chromatography is a resin.
The claims of copending Application No. 17/773,892 teach a method for purifying a multispecific protein comprising loading a sample comprising a multispecific protein onto a cation exchange chromatography medium; washing the cation exchange medium with at least one wash buffer comprising 100-147 mM sodium chloride; and eluting the multispecific protein from the cation exchange chromatography resin. The claims further teach wherein the wash buffer has a pH of between 4.9-5.1. The claims further teach wherein the wash buffer comprises acetate. The claims further teach additional wash buffers comprising 0-70 mM or 100-147 mM sodium chloride. The claims further teach wherein the multispecific protein is eluded by a linear gradient or a salt gradient. The claims further teach wherein the multispecific protein is a bispecific antibody. The claims further teach wherein the composition is loaded at 10-40 g/L. The claims of further teach that the cation exchange chromatography is a resin.
The claims of copending Application No. 17/773,892 do not teach an equilibration buffer comprising NaCl and acetate, a loading buffer comprising NaCl and acetate or the pH of the loading buffer.
Lee et al. teach a method for separating antibody isoforms using cation exchange chromatography comprising loading an antibody-containing sample onto a cation exchange chromatography column equilibrated with an equilibration buffer; washing the column with a washing buffer and recovering a target antibody from the column using an elution buffer (abstract and paras 0009-0026). Lee et al. teach various cation resins (para 0020). Lee et al. teach that as used herein, the term “antibody” or “immunoglobulin” refers to a protein consisting of one or more polypeptides substantially encoded by antibody genes. The recognized antibody genes include the different constant region genes as well as the myriad antibody variable region genes (para 0052)(i.e.,, multispecific). Lee et al. teach equilibrium buffers. Lee et al. teach the equilibrium buffer has a salt concentration of 10-300 mM or maybe 100 mM or less. Lee et al. teach the equilibrium buffer can comprise any one selected from the group consisting of sodium acetate and sodium chloride (paras 0010, 0014, 0024, 0033, 0035). Lee et al. teach wash buffers. Lee et al. teach the wash buffer has a salt concentration of 10-300 mM or maybe 100 mM or less. Lee et al. teach the wash buffer can comprise any one selected from the group consisting of sodium acetate and sodium chloride. Lee et al. teach more than one wash (paras 0011, 0025, 0032, 0079 and 0095). Lee et al. teach the pH of the wash buffer is between 5.0-8.0 (para 0027). Lee et al. teach that the pH and salt concentration conditions of the washing buffer are applied to the loading conditions of the cation exchange chromatography column, antibody isoforms can be separated in the same or similar manner (para 0045). Lee et al. teach wherein the multispecific protein is eluted from the cation exchange resin by a linear salt gradient (paras 0048-0051).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a method of using cation exchange chromatography to isolate/purify multispecific proteins, wherein the wash buffer comprises 100-147 mM sodium chloride, as taught by the claims of copending Application No. 17/773,892 by using an equilibration buffer and a load buffer comprising 10-300 mM NaCl, 100 mM or less and acetate, as taught by Lee et al. One of ordinary skill in the art at the time the invention was made would have been motivated to make such modifications and expect success for the following reasons. Both Copending Application No. 17/773,892 and Lee et al. teach using cation exchange chromatography to isolate/purify multispecific wherein the wash buffers comprises sodium chloride and acetate and overlap in the concentration ranges of sodium chloride. Lee et al. teach using equilibrium buffers and load buffers with sodium chloride and acetate in the same concentration ranges, which will maximize the interaction of the multispecific protein with the cation resin. This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/R.M.D/Examiner, Art Unit 1647 11/25/2025
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647