Prosecution Insights
Last updated: April 19, 2026
Application No. 17/642,870

METHODS AND COMPOSITIONS COMPRISING AN ANTI-CTLA4 MONOCLONAL ANTIBODY WITH REDUCED HOST CELL PROTEINS AND INCREASED POLYSORBATE-80 STABILITY

Non-Final OA §102§103§112
Filed
Mar 14, 2022
Examiner
DUFFY, BRADLEY
Art Unit
1643
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Merck Sharp & Dohme LLC
OA Round
1 (Non-Final)
54%
Grant Probability
Moderate
1-2
OA Rounds
3y 8m
To Grant
99%
With Interview

Examiner Intelligence

Grants 54% of resolved cases
54%
Career Allow Rate
396 granted / 729 resolved
-5.7% vs TC avg
Strong +45% interview lift
Without
With
+45.4%
Interview Lift
resolved cases with interview
Typical timeline
3y 8m
Avg Prosecution
47 currently pending
Career history
776
Total Applications
across all art units

Statute-Specific Performance

§101
3.2%
-36.8% vs TC avg
§103
27.9%
-12.1% vs TC avg
§102
19.7%
-20.3% vs TC avg
§112
29.8%
-10.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 729 resolved cases

Office Action

§102 §103 §112
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 . DETAILED ACTION The election without traverse filed June 3, 2025, is acknowledged and have been entered. Applicant has elected Group II and a species of antibody comprising a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO: 19 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:20 which comprises heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID Nos: 11, 12, and 13 and light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID Nos: 14, 15, and 16. Claims 1-6, 11-19, 22-24, 26, 33-34 and 41-44 are pending. Claims 42 and 44 are withdrawn from further consideration by the examiner, under 37 CFR 1.142(b), as being drawn to a non-elected invention or species of election. Claims 1-6, 11-19, 22-24, 26, 33-34, 41 and 43 are under examination. Claim Rejections-35 U.S.C. § 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. Claim 1 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 pre-AIA the applicant regards as the invention. The claim is indefinite because it recites “wherein the level of PLBL2, LPLA2, and LPL are ≤1 ng/ml of CTLA4 antibody”. This renders the claims unclear because it is unclear how the level of PLBL2, LPLA2, and LPL are ≤ 1 ng/ml of CTLA4 antibody”. The concentration of PLBL2, LPLA2, and LPL may be ≤ 1 ng/ml, but it is unclear what is meant by ≤ 1 ng/ml of CTLA4 antibody . Therefore, the claim fails to delineate the metes and bounds of the subject matter that Applicant regards as the invention with the requisite clarity and particularity to permit the skilled artisan to know or determine infringing subject matter. Accordingly, this claim is indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim Rejections - 35 USC § 102 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 1 is rejected under 35 U.S.C. 102(a)(1) or (2) as being anticipated by Abate et al (US 2009/0130119 A1). Abate et al discloses pharmaceutical compositions comprising CTLA antibody at 20mg/ml, 5mM EDTA (antioxidant), 20mM histidine buffer, 0.2mg/ml polysorbate 80(about 0.02%) and 84mg/ml of trehalose (about 8%) as in claim 1 of the instant application (see pages 5 and 20 and claims 1-20). As the prior art is silent about the level of PLB2, LPLA2 and LPL and the instant claim is unclear, the prior art anticipates the instant claim because the prior art includes compositions without any level of PLB2, LPLA2 and LPL and the instant claim is being reasonably interpreted to encompass such compositions without any level of PLB2, LPLA2 and LPL. Therefore, the products of the prior art are deemed to anticipate the instant claim absent a showing otherwise. 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 of this title, 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. 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. Claims 1-6, 11-19, 24, 26, 33-34, 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Abate et al (US 2009/0130119 A1), Lee et al (US 2018/0179545 A1, IDS) and Duthe et al (US 2016/0083454 A1). Abate et al discloses pharmaceutical compositions comprising CTLA antibody at 20mg/ml, 5mM EDTA (antioxidant), 20mM histidine buffer, 0.2mg/ml polysorbate 80(about 0.02%) and 84mg/ml of trehalose (about 8%) as in claim 1 of the instant application (see pages 5 and 20 an claims 1-20). Abate et al further discloses that the composition can comprise methionine at 1mM and/or sucrose and the antibody at a concentration of 25 mg/ml or 50 mg/ml (see pages 4, 8, 18 and 21). Lee et al discloses that it is desirable to make an antibody composition from a cell with about 95% reduction in endogenous lipase by genetically engineering the cell to reduce lipase expression and further removing the endogenous lipase so that the lipase is present at less than 0.0001% by weight (less than 2 ppm) (see claims and pages 1-2). Duthe et al discloses that it is desirable to use methods of purifying antibodies from host cell proteins including lipases by using purification steps including a protein A chromatography step, an anion exchange chromatography step, and a cation exchange step (see pages 1-3, 7-9 and claims) that are indistinguishable from the instant recited steps in the claimed product-by-process claims. Accordingly, it would have been obvious to one of ordinary skill in the art to make compositions encompassed by the claims by taking the cells of Abate that produce the CTLA4 antibody and genetically engineering the cells to reduce lipase expression and further removing any endogenous lipase using purification steps including a protein A chromatography step, an anion exchange chromatography step, and a cation exchange step so that the lipase is present at less than 0.0001% by weight (less than 2 ppm) because the prior art of Lee et al and Duthe et al disclose that it is desirable to remove lipases and other host cell proteins when producing antibodies such that one of skill in the art would have been motivated to produce and purify the CTLA4 antibodies accordingly and then place them in the compositions of Abate et al. Then as such compositions and methods of removing host cell lipases were disclosed one of skill in the art would have been able to make such compositions. Notably, absent a showing otherwise, these suggested compositions would have the claimed residual amounts of lipases and stability of PS-80 and meet the limitations otherwise set forth in these claims because they are produced by methods indistinguishable from those instantly recited. Applicant is reminded that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made. Claims 1-6, 11-19, 22-24, 26, 33-34, 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Abate et al (US 2009/0130119 A1), Lee et al (US 2018/0179545 A1, IDS) and Duthe et al (US 2016/0083454 A1) as applied to claims 1-6, 11-19, 24, 26, 33-34, 41 and 43 above, and further in view of Li et al (US 2017/0216433 A1, IDS). Claims 22-23 are further drawn to the CTLA4 antibody comprising a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO: 19 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:20. Li et al disclose a CTLA4 antibody comprising a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO: 6 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:8, which are 100% identical to instant SEQ ID NO: 19 and SEQ ID NO:20 and compositions thereof for treating cancer (see alignments, claims and pages 4-10). RESULT 1 US-15-500-744-6 (NOTE: this sequence has 10 duplicates in the database searched. See complete list at the end of this report) Sequence 6, US/15500744 Publication No. US20170216433A1 GENERAL INFORMATION APPLICANT: AKESO BIOPHARMA, INC. TITLE OF INVENTION: ANTI-CTLA4 MONOCLONAL ANTIBODY OR ANTIGEN TITLE OF INVENTION: BINDING FRAGMENT THEREOF, MEDICINAL TITLE OF INVENTION: COMPOSITION AND USE FILE REFERENCE: IEC150044PCT CURRENT APPLICATION NUMBER: US/15/500,744 CURRENT FILING DATE: 2017-01-31 PRIOR APPLICATION NUMBER: 201410377352.9 PRIOR FILING DATE: 2014-08-01 NUMBER OF SEQ ID NOS: 34 SEQ ID NO 6 LENGTH: 115 TYPE: PRT ORGANISM: Artificial sequence FEATURE: OTHER INFORMATION: the amino acid sequence of the heavy chain variable domain of the monoclonal antibody 8D2 Query Match 100.0%; Score 623; Length 115; Best Local Similarity 100.0%; Matches 115; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 EVKLDETGGGLVQPGRPMKLSCVASGFTFSDNWMNWVRQSPEKGLEWLAQIRNKPYNYET 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 EVKLDETGGGLVQPGRPMKLSCVASGFTFSDNWMNWVRQSPEKGLEWLAQIRNKPYNYET 60 Qy 61 YYSDSVKGRFTISRDDSKSSVYLQMNNLRGEDMGIYYCTAQFAYWGQGTLVTVSA 115 ||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 YYSDSVKGRFTISRDDSKSSVYLQMNNLRGEDMGIYYCTAQFAYWGQGTLVTVSA 115 RESULT 1 US-15-500-744-8 (NOTE: this sequence has 11 duplicates in the database searched. See complete list at the end of this report) Sequence 8, US/15500744 Publication No. US20170216433A1 GENERAL INFORMATION APPLICANT: AKESO BIOPHARMA, INC. TITLE OF INVENTION: ANTI-CTLA4 MONOCLONAL ANTIBODY OR ANTIGEN TITLE OF INVENTION: BINDING FRAGMENT THEREOF, MEDICINAL TITLE OF INVENTION: COMPOSITION AND USE FILE REFERENCE: IEC150044PCT CURRENT APPLICATION NUMBER: US/15/500,744 CURRENT FILING DATE: 2017-01-31 PRIOR APPLICATION NUMBER: 201410377352.9 PRIOR FILING DATE: 2014-08-01 NUMBER OF SEQ ID NOS: 34 SEQ ID NO 8 LENGTH: 106 TYPE: PRT ORGANISM: Artificial sequence FEATURE: OTHER INFORMATION: the amino acid sequence of the light chain variable domain of the monoclonal antibody 8D2 Query Match 100.0%; Score 549; Length 106; Best Local Similarity 100.0%; Matches 106; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 DIQMTQSPASLSASVGETVTITCGTSENIYGGLNWYQRKQGKSPQLLIFGATNLADGMSS 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 DIQMTQSPASLSASVGETVTITCGTSENIYGGLNWYQRKQGKSPQLLIFGATNLADGMSS 60 Qy 61 RFSGSGSGRQYSLKISSLHPDDVATYYCQNVLRSPFTFGSGTKLEI 106 |||||||||||||||||||||||||||||||||||||||||||||| Db 61 RFSGSGSGRQYSLKISSLHPDDVATYYCQNVLRSPFTFGSGTKLEI 106 Accordingly, it would have been obvious to one of ordinary skill in the art to substitute the CTLA4 antibody of Li et al for the CTLA4 antibodies in the compositions suggested above because the CTLA4 antibody of Li et al was a known CTLA4 antibody that could be used to treat cancer. Therefore, using the CTLA4 antibody of Li et al would be seen as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Furthermore, one of ordinary skill in the art would have expected success in making such compositions because the antibody was known in the art and methods of making CTLA4 antibody compositions were known in the art. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Conclusion No claims are allowed. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Zhang et al (US 2021/0008199 A1) disclose making compositions comprising antibodies with reduced host cell proteins using various methods including, inter alia, using anti-lipase antibodies to remove lipases. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner can normally be reached on Monday through Friday. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. Respectfully, Brad Duffy 571-272-9935 /Brad Duffy/ Primary Examiner, Art Unit 1643 October 1, 2025
Read full office action

Prosecution Timeline

Mar 14, 2022
Application Filed
Sep 20, 2023
Response after Non-Final Action
Oct 01, 2025
Non-Final Rejection — §102, §103, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
54%
Grant Probability
99%
With Interview (+45.4%)
3y 8m
Median Time to Grant
Low
PTA Risk
Based on 729 resolved cases by this examiner. Grant probability derived from career allow rate.

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