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 .
Election/Restrictions
Applicant’s election of group 1 in the reply filed on 8/20/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 53-54 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 8/20/2026.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/21/2025 and 8/20/2026 have been considered by the examiner.
Claim Rejections - 35 USC § 103
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.
Claims 1, 4-5, 7-8, 10-11, 13-14, 16-17, 19, 21, 23, 25-26, 30, 33-35, 37-40, 44, 46-48 and 53-54 are rejected under 35 U.S.C. 103 as being unpatentable over Mahajan et al. (PG Pub U.S 2019/0054396).
Regarding claim 1, Mahajan teaches a method for cleaning a protein A chromatography matrix (para 0055-0056), the method comprising sequentially washing a chromatography column comprising the protein A chromatography matrix (para 0095 and 0369; can be repeated reads on sequence) with: a) a first solution comprising one or more acid selected from the group consisting of acetic acid and phosphoric acid (claims 4-5 and para 0099); b) a second solution comprising Tris (claims 4-5 and para 0099); and c) a third solution comprising NaOH (claims 4-5 and para 0099).
Mahajan fails to specifically teach 0.001-0.075 M NaOH. However, since Mahajan teaches the third solution comprising about 0.1 M NaOH (.075 reads on about 0.1) (claims 4-5 and para 0099), it is reasonably expected to one of ordinary skill in the art that the molarity of NaOH can be between 0.001-0.075 M NaOH.
Regarding claim 4, Mahajan teaches wherein the first solution comprises acetic acid and phosphoric acid (para 0120, 0311, and 0350).
Regarding claim 5, the amount/concentration of acetic acid in the first solution is a result effective variable. Mahajan teaches the amount/concentration affects the conductivity (para 0121). Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate amount/concentration in order to achieve desired conductivity and cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount/concentration of the acetic acid such that such that it is 0.5-5% in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
Regarding claim 7, the amount/concentration of acetic acid in the first solution is a result effective variable. Mahajan teaches the amount/concentration affects the conductivity (para 0121). Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate amount/concentration in order to achieve desired conductivity and cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount/concentration of the acetic acid such that such that it is 1% in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
Regarding claim 8, the amount/concentration of phosphoric acid in the first solution is a result effective variable. Mahajan teaches the amount/concentration affects the conductivity (para 0121). Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate amount/concentration in order to achieve desired conductivity and cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount/concentration of the phosphoric acid such that such that it is 0.5-5% in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
Regarding claim 10, the amount/concentration of phosphoric acid in the first solution is a result effective variable. Mahajan teaches the amount/concentration affects the conductivity (para 0121). Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate amount/concentration in order to achieve desired conductivity and cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount/concentration of the phosphoric acid such that such that it is 1% in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
Regarding claim 11, the amount/concentration of acetic and phosphoric acid in the first solution is a result effective variable. Mahajan teaches the amount/concentration affects the conductivity (para 0121). Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate amount/concentration in order to achieve desired conductivity and cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount/concentration of acetic and phosphoric acid such that such that it is about 1% for both in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
16. Regarding claim 13, Mahajan teaches wherein the second solution has a pH of about 8. (para 0272 and claim 18).
17. Regarding claim 14, Mahajan teaches wherein the second solution comprises 10-100 mM Tris. (para 0272 and claim 18).
18. Regarding claim 16, Mahajan teaches wherein the second solution comprises about 50 mM Tris. (para 0272 and claim 18).
19. Regarding claim 17, Mahajan fails to specifically teach 0.005-0.05 M NaOH. However, since Mahajan teaches the third solution comprising about 0.1 M NaOH (.05 reads on about 0.1) (claims 4-5 and para 0099), it is reasonably expected to one of ordinary skill in the art that the molarity of NaOH can be between 0.005-0.05 M NaOH.
20. Regarding claim 19, Mahajan fails to specifically teach 0.01 M NaOH. However, since Mahajan teaches the third solution comprising about 0.1 M NaOH (.1 reads on about 0.01) (claims 4-5 and para 0099), it is reasonably expected to one of ordinary skill in the art that the molarity of NaOH can be 0.01 M NaOH.
21. Regarding claim 21, Mahajan teaches wherein the protein A chromatography matrix is washed with 2-3 column volumes of the first solution (para 0114).
22. Regarding claim 23, Mahajan teaches wherein the protein A chromatography matrix is washed with 1-2 column volumes of the second solution (para 0114).
23. Regarding claim 25, Mahajan teaches wherein the protein A chromatography matrix is washed with 2-3 column volumes of the third solution (para 0114).
24. Regarding claim 26, Mahajan teaches wherein the protein A chromatography matrix is washed with the first solution at a flow rate of about 270 cm/hr and is washed with the second solution at a flow rate of about 270 cm/hr and is washed with the third solution at a flow rate of about 270 cm/hr (para 0114-0115; based on cv/hr and height).
25. Regarding claim 30, Mahajan teaches wherein the chromatography column has a diameter of about 100 cm and an average particle size of about 85 um (0116-0017).
26. Regarding claim 33, Mahajan teaches wherein the protein A chromatography matrix a comprises a protein A ligand that has increased stability under alkali conditions relative to wild type Staphylococcus aureus protein A (para 0205 and 0300).
27. Regarding claim 34, Mahajan teaches: a) a first solution of acetic acid and phosphoric acid (claims 4-5, 0311 and 0350); b) a second solution comprising 50 mM Tris at a pH of about 8 (claims 4-5, para 0099 and 0272); and c) a third solution comprising NaOH (claims 4-5 and para 0099).
28. The amount/concentration of acetic and phosphoric acid in the first solution is a result effective variable. Mahajan teaches the amount/concentration affects the conductivity (para 0121). Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate amount/concentration in order to achieve desired conductivity and cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount/concentration of acetic and phosphoric acid such that such that it is about 1% for both in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
29. Mahajan fails to specifically teach 0.01 M NaOH. However, since Mahajan teaches the third solution comprising about 0.1 M NaOH (.1 reads on about 0.01) (claims 4-5 and para 0099), it is reasonably expected to one of ordinary skill in the art that the molarity of NaOH can be 0.1 M NaOH.
30. Regarding claim 35, Mahajan teaches wherein the protein A chromatography matrix is washed with: a) 2-3 column volumes of the first solution (para 0114); b) 1-2 column volumes of the second solution (para 0114); and c) 2-3 column volumes of the third solution (para 0114).
31. Regarding claim 37, Mahajan teaches comprising washing the protein A chromatography matrix with about 2 column volumes of the second solution after the protein A chromatography matrix is washed with the third solution (para 0095, 0114, and and 0369; can be repeated reads on sequence).
32. Regarding claim 38, Mahajan teaches washing the protein A chromatography matrix with a fourth solution comprising NaOH (para 0095 and 0369; can be repeated reads on fourth solution). Mahajan fails to specifically teach 0.01 M NaOH. However, since Mahajan teaches the third solution comprising about 0.1 M NaOH (.1 reads on about 0.01) (claims 4-5 and para 0099), it is reasonably expected to one of ordinary skill in the art that the molarity of NaOH can be 0.1 M NaOH.
33. Regarding claim 39, Mahajan teaches wherein the protein A chromatography matrix is washed with about 2 column volumes of the fourth solution (para 0114).
34. Regarding claim 40, Mahajan teaches wherein the protein A chromatography matrix is washed with the fourth solution at a flow rate of 100-140 cm/hr for about 25 minutes (para 0114-0115).
35. Regarding claim 44, Mahajan teaches wherein the protein A chromatography matrix has less than 0.1% carryover from the previous use after the protein A chromatography matrix is cleaned (para 0308).
36. Regarding claim 46, Mahajan fails to teach wherein the protein A chromatography matrix is used for 300-400 cycles of dulaglutide purification. The number of cycles of dulaglutide purification is a result effective variable. Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate cycles of dulaglutide purification in order to achieve desired cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the number of cycles of dulaglutide purification such that such that it is 300-400 in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
37. Regarding claim 47, Mahajan fails to teach wherein the protein A chromatography matrix is used for about 304 cycles of dulaglutide purification. The number of cycles of dulaglutide purification is a result effective variable. Without evidence of unexpected results, it would have been obvious to one or ordinary skill in the art before the effective filing date of the claimed invention to determine the appropriate cycles of dulaglutide purification in order to achieve desired cleaning. Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the number of cycles of dulaglutide purification such that such that it is about 304 in order to achieve desired conductivity and cleaning. See MPEP 2144.05 II.
38. Regarding claim 48, Mahajan teaches wherein the method does not include a static hold of any of the first solution, the second solution or the third solution (para 0095).
Conclusion
39. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRADHUMAN PARIHAR whose telephone number is (571)270-1633. The examiner can normally be reached Monday-Friday 10am-6pm EST.
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/P.P/Examiner, Art Unit 1714
/KAJ K OLSEN/Supervisory Patent Examiner, Art Unit 1714
