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 .
Claim Status
Claims 2, 9, 14 and 16 were canceled.
Claims 1, 3-8, 10-13, 15 and 17-21 are pending.
Claims 1, 3-7, 15 and 17-21 stay withdrawn from further consideration.
Claims 8 and 10-13 are under consideration.
Withdrawn Rejections
Rejection of Claim 14 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of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn. Applicant canceled claim 14 and therefore this rejection is moot.
Rejection of Claim(s) 8 and 10-14 under 35 U.S.C. 102(a)(1) as being anticipated by Pippig et al (WO2018/024770) is withdrawn. Applicant added new step (d) to claim 8 to overcome this rejection.
Claim Rejections - 35 USC § 112
(necessitated by amendments)
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 8 and 10-13 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.
Amended claim 8 now recites a new process step (d) of “determining the oligosaccharide profile”. The method of producing antibody of claim 8 are performed by (a) culturing CHO cell, (b) expressing antibody in CHO cell, and (c) purifying the expressed antibody. The new process step (d) of “determining the oligosaccharide profile” is not required process step of producing antibody. Instead, it is analysis process after producing the antibody. Therefore, it is unclear how this analysis step (d) can be required process step of the method of producing antibody of claim 8.
Same reasoning applies to claims 10-11 because amended claims 10-11 recite step of “determining the oligosaccharide profile”.
Dependent claims 12-13 are also rejected because they depend from claim 8 and therefore contain same claim limitation as claim 8.
Claim Rejections - 35 USC § 103
(necessitated by amendments)
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.
Claim(s) 8 and 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pippig et al (WO2018/024770; published 2/8/2018; 3/28/2025 11-page IDS).
Regarding claim 8, Pippig teaches “The present invention relates to a method for producing an ustekinumab antibody in CHO cells” (abstract). Pippig teaches “A method of producing a recombinant ustekinumab antibody drug product comprising the heavy chain and the light chain of ustekinumab, wherein the heavy chain has the sequence according to SEQ ID No. 1 and the light chain has the sequence according to SEQ ID No. 2 and wherein the heavy chain and the light chain together form the recombinant ustekinumab antibody, the method comprising: a) culturing Chinese Hamster Ovary (CHO) host cells, genetically modified to express the heavy chain and the light chain of ustekinumab, in a suitable culture medium under conditions that allow the cells to express the heavy chain and the light chain and to form the recombinant ustekinumab antibody; b) harvesting the recombinant ustekinumab antibody from the host cell culture to obtain a recombinant ustekinumab antibody preparation; c) optionally purifying the recombinant ustekinumab antibody preparation obtained in step b) by one or more purification step(s)” (claim 1). Pippig teaches “Method according to any one of the preceding claims, wherein the CHO host cells are CHO-K1 cells or cells derived therefrom” (claim 7). The ustekinumab of instant invention was also expressed in CHO-K1 cell as evidenced by page 75 of instant specification. Pippig teaches ustekinumab heavy chain SEQ ID NO: 1 which is 100% identical to instant SEQ ID NO: 10 (duplicate of result 1 of 10.rag). Pippig teaches ustekinumab heavy chain SEQ ID NO: 2 which is 100% identical to instant SEQ ID NO: 11 (duplicate of result 1 of 11.rag). The heavy chain of SEQ ID NO: 10 comprises VH of SEQ ID NO: 7 and H-CDRs of SEQ ID NO: 1, 2 and 3. The light chain of SEQ ID NO: 11 comprises VL of SEQ ID NO: 8 and L-CDRs of SEQ ID NO: 4, 5 and 6. Therefore, ustekinumab taught by Pippig comprises SEQ ID NOs recited by instant claim 8.
The difference between prior art and the instant invention is that Pippig does not expressly teach the step (d) of “determining the oligosaccharide profile”.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have determined the oligosaccharide profile of the produced ustekinumab by well-known analysis process.
As evidenced by instant specification, a point of control for the oligosaccharide profile of therapeutic antibodies is the selection of the cellular host for expression of the therapeutic antibodies (page 94, line 2-5). Instant specification further disclosed the difference of oligosaccharide profile of ustekinumab expressed in Sp2/0 cells and CHO cells (page 94-95). Instant specification disclosed that the oligosaccharide profile of ustekinumab produced in CHO cells comprises total neutral oligosaccharide species > 99.0%, total charged oligosaccharide species < 1.0%, and individual neutral oligosaccharide species G0F > 70.0%, G1F < 20.0%, and G2F < 5.0% (page 94, line 17-30). The peak 3 area % of the capillary isoelectric focusing (cIEF) electropherogram of ustekinumab produced in CHO cells is > 70.0%. Furthermore, no disialylated glycan species were detected by IRMA or by HPLC for ustekinumab produced in CHO cells and monosialylated glycan species were at very low levels based on HPLC analysis and undetectable by IRMA analysis. The reduction in sialylated species generally and the reduction of Neu5Gc specifically for ustekinumab produced in CHO cells may provide a benefit by reducing undesirable immunogenic responses when administered to humans. For example, reduced levels of Neu5Gc could reduce clearance so that anti-IL-12/23p40 antibodies produced in CHO cells would have a longer half-life compared to anti-IL-12/23p40 antibodies expressed in Sp2/0 cells, especially for patient populations with higher levels of anti-Neu5Gc antibodies (page 95). Therefore, as evidenced by the instant specification, the ustekinumab of Pippig that is expressed in same CHO-K1 cell will have the same oligosaccharide profile as instant invention because oligosaccharide profile is determined by host expression cell line. Therefore, the functional property of ustekinumab is the inherent characteristics of ustekinumab expressed in CHO cell.
Therefore, one of ordinary skill in the art would be motivated to determine the oligosaccharide profile of the produced ustekinumab because Pippig teaches same therapeutic antibody ustekinumab expressed in CHO-K1 cell as instant invention. One of ordinary skill in the art would be motivated to study the inherent characteristics of this therapeutic antibody ustekinumab expressed in CHO-K1 cell because one of ordinary skill in the art would understand that knowing characteristics of therapeutic antibody is important for administering the therapeutic antibody ustekinumab into human subject. Therefore, inherent characteristics recited by claims 8 and 10-13 are obvious because it can be determined by obvious technique well known in the art and because it is inherent characteristics of ustekinumab expressed in same CHO-K1 cell taught by Pippig as instant invention. Furthermore, process step of determining the oligosaccharide profile by well-known analysis method such as capillary isoelectric focusing, HPLC, Reduced Mass Analysis recited by claims 11-12 are conventionally performed and well-known routine experimentation in the art. Therefore, claims 8 and 10-13 are obvious to one of ordinary skill in the art. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because process step of determining the oligosaccharide profile by well-known analysis method such as capillary isoelectric focusing, HPLC, Reduced Mass Analysis recited by instant claims are conventionally performed and well-known routine experimentation in the art. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHEOM-GIL CHEONG whose telephone number is (571)272-6251. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674