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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 17/777,385, filed on 5/17/22.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 3/10/26 is acknowledged.
Claim Status
Claims 1-30 are pending.
Claims 28-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 3/10/26.
Claims 1-27 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statements filed on 10/21/25, 12/19/25, and 1/30/26 have been considered. Signed copies are enclosed.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or 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 IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim subparts are designated with a period. Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). It is recommended that the claim subparts be designated with parentheses, such as “(a)” or “a)”. Appropriate correction is required.
Claim 3 is objected to because of the following informalities: the term “SEC” contains an acronym and/or abbreviation that should be spelled out upon first occurrence. Appropriate correction is required.
Claims 5, 6, 13, 17, 18, 23, and 24 are objected to because of the following informalities: the phrase “wherein the processing the adjusted sample” should be amended to recite proper grammar, such as “wherein the processing of the adjusted sample”. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: the term “anti-IL-17” contains an acronym and/or abbreviation that should be spelled out upon first occurrence. 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.
Claim 12 is 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.
Claim 12 recites the term “about”. The term “about” is not defined in the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-27 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Giese et al (WO 2017/218977 A2; filed 6/16/17; published 12/21/17).
Claim 1 is directed to a method of producing an antibody composition, comprising purifying an IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody in a composition, wherein the pH of the sample in step b) and/or the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of a salt.
Claim 2 is directed to the method of claim 1, wherein the pH of the sample in step b) and the pH and conductivity of the sample in step c) are adjusted with Tris in the absence of the salt.
Claim 3 method of claim 1, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 4 is directed to method of claim 1, wherein the collected antibody has a SEC monomer content of at least 99%.
Claim 5 is directed to the method of claim 1, wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 6 is directed to the method of claim 1, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 7 is directed to the method of claim 6, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 8 is directed to the method of claim 1, wherein the antibody is a human monoclonal antibody.
Claim 9 is directed to the method of claim 8, wherein the antibody is an anti-IL-17 antibody.
Claim 10 is directed to the method of claim 1, wherein the ion exchange chromatography is anion exchange chromatography.
Claim 11 is directed to the method of claim 1, wherein the ion exchange chromatography is performed in bind-and-elute mode.
Claim 12 is directed to the method of claim 1, wherein the second pH is about pH 5.2 to about pH 5.6.
Claim 13 is directed to the method of claim 8, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 14 is directed to the method of producing an antibody composition, comprising purifying an IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody, wherein the pH of the sample in step b) and/or the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of NaCI.
Claim 15 is directed to the method of claim 14, wherein the antibody is an anti-IL-17 antibody.
Claim 16 is directed to the method of claim 14, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 17 is directed to the method of claim 14,wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 18 is directed to the method of claim 14, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 19 is directed to the method of claim 18, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 20 is directed to a method of producing an antibody composition, comprising purifying an anti-IL-17 IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody, wherein the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of NaCI.
Claim 21 is directed to the method of claim 20, wherein the pH of the sample in step b) is adjusted with Tris in the absence of NaCI.
Claim 22 is directed to the method of claim 20, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 23 is directed to the method of claim 20, wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 24 is directed to the method of claim 20, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 25 is directed to the method of claim 24, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 26 is directed to the method of claim 24, wherein the ion exchange chromatography is anion exchange chromatography.
Claim 27 is directed to the method of claim 25, wherein the ion exchange chromatography is performed in bind-and-elute mode.
Regarding the limitations of instant claims 1-2, Giese teaches purification of multispecific antibodies that involves affinity chromatography using Protein A, followed by multimodal anion exchange chromatography in flow through mode (see e.g. Figure 1, and Abstract, see e.g. claim 88-89). Giese teaches that the desired pH and conductivity of the buffer can be adjusted as needed in the loading buffer or other buffers (see e.g. paragraph [0153]). Loading buffer is the buffer used to load the composition (see e.g. paragraph [0154]). The loading buffer can have a conductivity of greater than 10 mS/cm (see e.g. paragraph [0166]). The pH of the loading buffer can be 6.5, 7, or 7.5 (see e.g. paragraph [0175]). The buffer can comprise Tris HCL or Tris acetate (see e.g. paragraph [0153], [0165]). The chromatography can be carried out in flow-through mode (see e.g. paragraph [0012], [0013], [0223], claim 92). In one example, the antibody is purified by affinity chromatography using Protein A, then the pooled material from the protein A column was pH adjusted by addition of elution buffer to achieve a pH ≤ 3.60 and held for at least 120 minutes (see e.g. paragraph [0432]). Then the pH of the pooled material was adjusted to PH 5.0±0.3 (see e.g. paragraph [0432]). The adjusted assembled pool was subjected toa multimodal cation exchange column in a bind and elute mode (see e.g. paragraph [0434]). The eluate was also subjected to a multimodal anion exchange column (see e.g. paragraph [0435]). In another example, an antibody was purified via affinity chromatography in bind-elute mode, then adjusted to pH 3.5 with acetic acid for 30 min, then conditioned with 1.5M Tris Bas to pH 5.0, and then the pool was conditioned to pH 7 using 1.5M Tris base, then purified using a multimodal anion exchange column (see e.g. Example 6, paragraphs [0476]-[0479]). Giese describes the buffer as having “sodium chloride, Tris HCL, Tris acetate…or a mixture thereof” (see e.g. paragraph [0153]). This indicates that buffers both with and without sodium chloride are anticipated.
Regarding the limitations of instant claims 3-6, 13, 16-18, 22-24, Giese teaches the specific steps of the instant method, and therefore would inherently produce the required SEC monomer content and antibody yield. The process also is shown by Giese to produce 85% yield (see e.g. Table 1, paragraph [0224], Table 7-11 (page 99-101)). Giese teaches yields of 89% using the CAPTO Adhere column (see e.g. Table 15).
Regarding the limitations of instant claim 7, 19, 25, the antibody can be eluted off the column using an acetate buffer (see e.g. paragraph [0434], [0448]-[0449])
Regarding the limitations of instant claim 8, Giese teaches that the antibody can be a monoclonal antibody (see e.g. paragraph [0245]).
Regarding the limitations of instant claim 9 and 15, Giese teaches that the purified antibody can bind to IL-17c (see e.g. paragraph [0397]).
Regarding the limitations of instant claims 10, and 26, Giese teaches purification of multispecific antibodies that involves affinity chromatography using Protein A, followed by multimodal anion exchange chromatography in flow through mode (see e.g. Figure 1, and Abstract, see e.g. claim 88-89).
Regarding the limitations of instant claim 11 and 27, the ion exchange chromatography can be performed in bind-and-elute mode.
Regarding the limitations of instant claim 12, Giese teaches that the eluate from the Protein A column can have a pH adjusted to around 5.0 (see e.g. paragraph [0432]).
Regarding the limitations of instant claim 14 and 20-21, Giese teaches purification of multispecific antibodies that involves affinity chromatography using Protein A, followed by multimodal anion exchange chromatography in flow through mode (see e.g. Figure 1, and Abstract, see e.g. claim 88-89). Giese teaches that the desired pH and conductivity of the buffer can be adjusted as needed in the loading buffer or other buffers (see e.g. paragraph [0153]). Loading buffer is the buffer used to load the composition (see e.g. paragraph [0154]). The loading buffer can have a conductivity of greater than 10 mS/cm (see e.g. paragraph [0166]). The pH of the loading buffer can be 6.5, 7, or 7.5 (see e.g. paragraph [0175]). The buffer can comprise Tris HCL or Tris acetate (see e.g. paragraph [0153], [0165]). The chromatography can be carried out in flow-through mode (see e.g. paragraph [0012], [0013], [0223], claim 92). In one example, the antibody is purified by affinity chromatography using Protein A, then the pooled material from the protein A column was pH adjusted by addition of elution buffer to achieve a pH ≤ 3.60 and held for at least 120 minutes (see e.g. paragraph [0432]). Then the pH of the pooled material was adjusted to PH 5.0±0.3 (see e.g. paragraph [0432]). The adjusted assembled pool was subjected toa multimodal cation exchange column in a bind and elute mode (see e.g. paragraph [0434]). The eluate was also subjected to a multimodal anion exchange column (see e.g. paragraph [0435]). In another example, an antibody was purified via affinity chromatography in bind-elute mode, then adjusted to pH 3.5 with acetic acid for 30 min, then conditioned with 1.5M Tris Bas to pH 5.0, and then the pool was conditioned to pH 7 using 1.5M Tris base, then purified using a multimodal anion exchange column (see e.g. Example 6, paragraphs [0476]-[0479]). Giese describes the buffer as having “sodium chloride, Tris HCL, Tris acetate…or a mixture thereof” (see e.g. paragraph [0153]). This indicates that buffers both with and without sodium chloride are anticipated. The antibody can be an IgG1 antibody (see e.g. paragraph [0088]).
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.
Claim 1-10 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,259,869 in view of Giese et al (WO 2017/218977 A2; filed 6/16/17; published 12/21/17).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 is directed to a method of producing an antibody composition, comprising purifying an IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody in a composition, wherein the pH of the sample in step b) and/or the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of a salt.
Claim 2 is directed to the method of claim 1, wherein the pH of the sample in step b) and the pH and conductivity of the sample in step c) are adjusted with Tris in the absence of the salt.
Claim 3 method of claim 1, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 4 is directed to method of claim 1, wherein the collected antibody has a SEC monomer content of at least 99%.
Claim 5 is directed to the method of claim 1, wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 6 is directed to the method of claim 1, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 7 is directed to the method of claim 6, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 8 is directed to the method of claim 1, wherein the antibody is a human monoclonal antibody.
Claim 9 is directed to the method of claim 8, wherein the antibody is an anti-IL-17 antibody.
Claim 10 is directed to the method of claim 1, wherein the ion exchange chromatography is anion exchange chromatography.
Claim 11 is directed to the method of claim 1, wherein the ion exchange chromatography is performed in bind-and-elute mode.
Claim 12 is directed to the method of claim 1, wherein the second pH is about pH 5.2 to about pH 5.6.
Claim 13 is directed to the method of claim 8, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 14 is directed to the method of producing an antibody composition, comprising purifying an IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody, wherein the pH of the sample in step b) and/or the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of NaCI.
Claim 15 is directed to the method of claim 14, wherein the antibody is an anti-IL-17 antibody.
Claim 16 is directed to the method of claim 14, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 17 is directed to the method of claim 14,wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 18 is directed to the method of claim 14, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 19 is directed to the method of claim 18, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 20 is directed to a method of producing an antibody composition, comprising purifying an anti-IL-17 IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody, wherein the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of NaCI.
Claim 21 is directed to the method of claim 20, wherein the pH of the sample in step b) is adjusted with Tris in the absence of NaCI.
Claim 22 is directed to the method of claim 20, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 23 is directed to the method of claim 20, wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 24 is directed to the method of claim 20, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 25 is directed to the method of claim 24, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 26 is directed to the method of claim 24, wherein the ion exchange chromatography is anion exchange chromatography.
Claim 27 is directed to the method of claim 25, wherein the ion exchange chromatography is performed in bind-and-elute mode.
The ‘869 patent teaches an anti-IL-17C antibody comprising heavy and light chain of SEQ ID NO:17 and 16, or SEQ ID NO:30 and 29 (see e.g. claims 1 and 5-6).
The ‘869 patent et al does not teach the method of instant claim 1 requiring ion exchange chromatography comprising the steps of: providing a sample comprising an antibody; adjusting the conductivity of the sample; processing the adjusted sample by ion exchange chromatography in flow-through mode and collecting the flow-through comprising the antibody, wherein the conductivity of the sample is adjusted with Tris. The reference patent does not teach the dependent claim limitations for the method steps.
Giese teaches purification of multispecific antibodies that involves affinity chromatography using Protein A, followed by multimodal anion exchange chromatography in flow through mode (see e.g. Figure 1, and Abstract, see e.g. claim 88-89). Giese teaches that the desired pH and conductivity of the buffer can be adjusted as needed in the loading buffer or other buffers (see e.g. paragraph [0153]). Loading buffer is the buffer used to load the composition (see e.g. paragraph [0154]). The loading buffer can have a conductivity of greater than 10 mS/cm (see e.g. paragraph [0166]). The pH of the loading buffer can be 6.5, 7, or 7.5 (see e.g. paragraph [0175]). The buffer can comprise Tris HCL or Tris acetate (see e.g. paragraph [0153], [0165]). The chromatography can be carried out in flow-through mode (see e.g. paragraph [0012], [0013], [0223], claim 92). In one example, the antibody is purified by affinity chromatography using Protein A, then the pooled material from the protein A column was pH adjusted by addition of elution buffer to achieve a pH ≤ 3.60 and held for at least 120 minutes (see e.g. paragraph [0432]). Then the pH of the pooled material was adjusted to PH 5.0±0.3 (see e.g. paragraph [0432]). The adjusted assembled pool was subjected toa multimodal cation exchange column in a bind and elute mode (see e.g. paragraph [0434]). The eluate was also subjected to a multimodal anion exchange column (see e.g. paragraph [0435]). In another example, an antibody was purified via affinity chromatography in bind-elute mode, then adjusted to pH 3.5 with acetic acid for 30 min, then conditioned with 1.5M Tris Bas to pH 5.0, and then the pool was conditioned to pH 7 using 1.5M Tris base, then purified using a multimodal anion exchange column (see e.g. Example 6, paragraphs [0476]-[0479]). Giese describes the buffer as having “sodium chloride, Tris HCL, Tris acetate…or a mixture thereof” (see e.g. paragraph [0153]). This indicates that buffers both with and without sodium chloride are anticipated. Giese teaches the specific steps of the instant method, and therefore would inherently produce the required SEC monomer content and antibody yield. The process also is shown by Giese to produce 85% yield (see e.g. Table 1, paragraph [0224], Table 7-11 (page 99-101)). Giese teaches yields of 89% using the CAPTO Adhere column (see e.g. Table 15). Giese teaches that the antibody can be eluted off the column using an acetate buffer (see e.g. paragraph [0434], [0448]-[0449]). Giese teaches that the antibody can be a monoclonal antibody (see e.g. paragraph [0245]). Giese teaches that the purified antibody can bind to IL-17c (see e.g. paragraph [0397]). Giese teaches purification of multispecific antibodies that involves affinity chromatography using Protein A, followed by multimodal anion exchange chromatography in flow through mode (see e.g. Figure 1, and Abstract, see e.g. claim 88-89). Giese teaches that the ion exchange chromatography can be performed in bind-and-elute mode. Giese teaches that the eluate from the Protein A column can have a pH adjusted to around 5.0 (see e.g. paragraph [0432]). Giese teaches purification of multispecific antibodies that involves affinity chromatography using Protein A, followed by multimodal anion exchange chromatography in flow through mode (see e.g. Figure 1, and Abstract, see e.g. claim 88-89). Giese teaches that the antibody can be an IgG1 antibody (see e.g. paragraph [0088]).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to purify the antibodies of the ‘869 patent as described by Giese to produce a pharmaceutically acceptable purity for the isolated antibody product. The ‘869 patent teaches the antibody of the instant claims, but fails to provide a method for purification that would produce a pharmaceutical-grade antibody product. Giese teaches that even standard purification processes for monoclonal antibodies often do not result in the antibody compositions of sufficient purity for use in pharmaceutical contexts (see e.g. Giese paragraphs [0004]-[0006]). Giese remedies this by providing methods that produce an antibody composition is substantially free of process- and product-related impurities (see e.g. Giese paragraphs [0004]-[0006]). It would be expected, absent evidence to the contrary, that applying the isolation process of Giese to the antibody of the reference patent would produce an increase in purity of the reference patent antibody that would allow it to be useful as a pharmaceutical grade product. The advantages of increased purity and production of a pharmaceutical quality product provide the motivation to purify the antibody of the ‘869 patent, based on the teachings of Giese, with a reasonable expectation of success.
Furthermore, one of ordinary skilled in the art would have been motivated to optimize the pH and conductivity of the composition at various points in the process, including to adjust conductivity, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); 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) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claims 1-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 17/777,385 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is directed to a method of producing an antibody composition, comprising purifying an IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody in a composition, wherein the pH of the sample in step b) and/or the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of a salt.
Claim 2 is directed to the method of claim 1, wherein the pH of the sample in step b) and the pH and conductivity of the sample in step c) are adjusted with Tris in the absence of the salt.
Claim 3 method of claim 1, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 4 is directed to method of claim 1, wherein the collected antibody has a SEC monomer content of at least 99%.
Claim 5 is directed to the method of claim 1, wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 6 is directed to the method of claim 1, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 7 is directed to the method of claim 6, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 8 is directed to the method of claim 1, wherein the antibody is a human monoclonal antibody.
Claim 9 is directed to the method of claim 8, wherein the antibody is an anti-IL-17 antibody.
Claim 10 is directed to the method of claim 1, wherein the ion exchange chromatography is anion exchange chromatography.
Claim 11 is directed to the method of claim 1, wherein the ion exchange chromatography is performed in bind-and-elute mode.
Claim 12 is directed to the method of claim 1, wherein the second pH is about pH 5.2 to about pH 5.6.
Claim 13 is directed to the method of claim 8, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 14 is directed to the method of producing an antibody composition, comprising purifying an IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody, wherein the pH of the sample in step b) and/or the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of NaCI.
Claim 15 is directed to the method of claim 14, wherein the antibody is an anti-IL-17 antibody.
Claim 16 is directed to the method of claim 14, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 17 is directed to the method of claim 14,wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 18 is directed to the method of claim 14, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 19 is directed to the method of claim 18, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 20 is directed to a method of producing an antibody composition, comprising purifying an anti-IL-17 IgG1 antibody by a process comprising the steps of: a) providing a sample with a first pH comprising the antibody; b) adjusting the first pH of the sample to a second pH; c) adjusting the conductivity of the sample and the second pH to a third pH; d) processing the adjusted sample by ion exchange chromatography; and e) collecting the antibody, wherein the pH and conductivity of the sample in step c) is adjusted with Tris in the absence of NaCI.
Claim 21 is directed to the method of claim 20, wherein the pH of the sample in step b) is adjusted with Tris in the absence of NaCI.
Claim 22 is directed to the method of claim 20, wherein the collected antibody has a SEC monomer content of at least 98%.
Claim 23 is directed to the method of claim 20, wherein the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 24 is directed to the method of claim 20, wherein the collected antibody has a SEC monomer content of at least 98%, and the processing the adjusted sample by ion exchange chromatography results in an antibody yield of at least 75%.
Claim 25 is directed to the method of claim 24, wherein the pH of the composition comprising the antibody collected in step e) is adjusted using an acetate buffer.
Claim 26 is directed to the method of claim 24, wherein the ion exchange chromatography is anion exchange chromatography.
Claim 27 is directed to the method of claim 25, wherein the ion exchange chromatography is performed in bind-and-elute mode.
The reference application teaches a method of producing an antibody composition comprising providing a sample with a first pH, adjusting the pH to a second pH, adjusting the conductivity of the sample and the second pH to a third pH, processing the adjusted sample by ion exchange chromatography and collecting the antibody in a composition (see e.g. reference claim 1). The pH and conductivity can be adjusted with Tris in the absence of salt (see e.g. reference claim 1). The yield from processing is at least 75% (see e.g. reference claim 5). The antibody can be a monoclonal antibody (see e.g. reference claim 8), and the antibody can be an anti-IL-17 antibody (see e.g. reference claim 9). The chromatography can be an anion exchange chromatography (see e.g. claim 10). The second pH is about 5.2 to about 5.6 (see e.g. reference claim 12).
The reference application teaches a method that is a species of the instant claimed genus. The scope of the two claim sets overlaps, but is not identical.
Conclusion
No claim is allowed.
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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