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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 12, 2026, has been entered.
DETAILED ACTION
The amendment filed February 12, 2026 in response to the Office Action of August 12, 2025 is acknowledged and has been entered.
Claims 10 and 27 have been amended.
Claims 7-9, 11, and 14-24 have been cancelled.
Claims 10, 13, and 25-27 are pending and under consideration.
NEW REJECTIONS
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.
Claims 10, 13, and 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Sound Biologics News (downloaded from: https://www.soundbiologics.com/news/press-releases/sound-biologics-announces-fda-allowance-of-its-ind-application-for-psb205/; Publication Date: April 10, 2019, of record), in view of Yan (Yan et al., Pub. No.: US 2019/0248899 A1, Publication Date: 08/15/2019, of record), Nathan (US 2018/0371092 A1, Publication Date: December 27, 2018, cited in IDS, of record) and Nguyen (Nguyen et al., Biotechnol. J., 2019, 14, 1900125, Publication Date: 08/09/2019).
Sound Biologics News teaches that U.S. Food and Drug Administration (FDA) has issued authorization to commence a Phase I First-in- PSB205 for the treatment of patients with relapsed/refractory solid tumors. PSB205 is an immune-oncology biotherapeutic that represents the first of a new class of therapeutic modality (see paragraph 1).
Sound Biologics News teaches that PSB205 is a novel bifunctional product that contains a mixture of unique anti-PD-1 and anti-CTLA4 monoclonal antibodies produced by a single cell line via the company's proprietary MabPair technology. MabPair products offer many advantages over bispecific antibodies. The relative ratio of the two antibodies in the MabPair can be well-controlled and each antibody is individually engineered for optimal target coverage, effector function, pharmacokinetics and exposure. PSB205 represents a potentially best-in-class immuno-oncology product that promises to exhibit robust combination activity while being significantly more tolerable to patients than currently approved anti-PD-1/anti-CTLA-4 combinations (see paragraph 2).
Sound Biologics (Qilu Puget Sound Biotherapeutic Corp.) is the applicant of the instant application.
Although Sound Biologics News does not disclose sequence information about the specific anti-PD-1 and anti-CTLA4 monoclonal antibodies. However, as evidenced by the instant specification, PSB205 is a mixture of PSB105 and PSB103 (see Example 5). In addition, PSB103 is an anti-hPD1 antibody comprising a heavy chain (HC) and a light chain (LC) with amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively (see Example 1, para. [0198] of US 2022/0267446 A1). PSB105 is an anti-hCTLA4 antibody comprising a heavy chain (HC) and a light chain (LC) with amino acid sequences of SEQ ID NO: 13 and SEQ ID NO: 17, respectively (§ Brief Description of the Sequence Listing, paragraph [0095] of US 2022/0267446).
Thus, PSB205 disclosed by Sound Biologics News reads on the anti-hPD1 antibody and anti-hCTLA4 antibody recited by instant claim 10.
Sound Biologics News teaches as set forth above. However, Sound Biologics News does not explicitly teach the nucleic acid sequences encoding the antibody or vectors or Chinese hamster ovary (CHO) cells comprising the nucleic acid, or a method of making the mixed antibodies with a ratio of 1:2.
Regarding the nucleic acid encoding the amino acid of heavy chains and light chains, it is noted that the courts have found that the disclosure of the polypeptide makes the nucleic acid encoding the protein obvious as the methods of obtaining the nucleic acids are routine in the art and can be obtained with a reasonable expectation of success. See MPEP 2143(E)(Example 3), Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007), and In re Kubin 90 USPQ2d 1417 (U. S. Court of Appeals Fed. Cir. 2009).
Yan teaches one of more nucleic acids encoding the antibody or the mixture of antibodies ([0374]).
Yan teaches one or more vector(s) containing the nucleic acid(s) encoding the antibody or the mixture of antibodies ([0375]).
Yan teaches the vectors can be viral vectors, such as AAV, MVA (claim 99, [0376] and [0377]).
Yan teaches a host cell line containing the nucleic acid and/or the vectors ([0378]).
Yan teaches a method of making a mixture of antibodies, comprising the steps of: (a) culturing the host cell line expressing the mixture of antibodies in a culture medium, and (b) recovering the mixture of antibodies from the cell mass or the culture medium ([0365-0367]).
Yan teaches the host cell line is a CHO cell line ([0368], [0509], claims 103-104).
Yan teaches method of generate DNA constructs encoding antibodies (Examples 2 and 3).
Yan teaches method of making a mixture of anti-PD-1 and anti-CTLA4 antibodies (claims 82, 96, Example 5, Table 21, Example 8).
Yan teaches that the single cell system can produce mixture with various anti-CTLA4:anti-PD1 ratios ([0604], Example 8, Table 27 and Table 28).
Nathan teaches a method of using anti-PD-1 antibody and anti-CTLA4 antibody in combination to treat human cancers (see Abstract), e.g. Nivolumab (human antibody to PD1) and Ipilimumab (human antibody to CTLA4) (see [0004], [0005], [0009], and [0010]).
Nathan teaches a fixed dose in which the weight to weight ratio of anti-CTLA4:anti-PD1 ratio can be 1:2 ([0055]).
Nathan teaches actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention can be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being unduly toxic to the patient. The selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions of the present invention employed, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts ([0129]).
Nguyen teaches a number of promoters derived from Chinese Hamster Ovary Cells which confer different expression levels (Fig. 2). The strength of the promoters ranges from very weak to very strong (Fig. 2).
Nguyen teaches that combinations of endogenous enhancers can further fine-tune expression levels (§ 3.4 Combinations of Endogenous Enhancers with Endogenous and Viral Core Promoters, on page 6).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention was filed and one would have been motivated to use the monoclonal antibodies taught by Sound Biologics News to obtain nucleic acid sequences, to make vector and host cells comprising the nucleic acid for making the mixture of anti-PD1 and anti-CTLA4 antibodies (PSB205), as taught by Yan. One would have been motivated to produce the nucleic acid encoding the antibodies, because Yan teaches that the isolation of the nucleic acid can be used to produce the mixture of antibodies with a proper vector and host cells and given that Yan teaches that the mixture of antibodies that target more than one antigen or epitope can be more effective.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to obtain an antibody mixture, e.g. PSB205, as taught by Sound Biologics News, and to use a weight to weight ratio of 1:2 between PSB103 and PSB105, and to use a cell line to produce desired ratio between the two antibodies, because MabPair provide a good platform to control each antibody for optimal function; Nathan teaches the ratio can be used for anti-CTLA4 and anti-PD1 antibody mixture for treatment; and Nguyen teaches various promoters and enhancers for fine-tuning protein expression in CHO cells. One of ordinary skilled in the art would have known and been motivated to make antibody mixture with a ratio as instantly claimed in CHO cells to achieve desired therapeutic effects, based on antibody pharmacokinetic factors and patient condition, as evidenced by Nathan. Based on the teachings of references, one of ordinary skill would have a reasonable expectation that using the promoters and/or enhancers taught by Nguyen and system taught by Yan, the ratio of anti-CTLA4 and anti-PD1 in the antibody mixture can be fine-tuned to a ratio of 1:2 in CHO cells. The motivation would be to simplify the production process by generate the antibody mixture in a single expressing cell line with a desired ratio.
Regarding claims 25-27, as evidenced by the instant specification, PSB105 (the anti-hCTLA4 antibody) has a T1/2 of 109 hours in single dose in cynomolgus monkeys (Table 2, Example 3). PSB103 (the anti-hPD1 antibody) has a T1/2 of 297 hours in single dose in cynomolgus monkeys (Table 1, Example 3).
Response to Arguments
For the 103 rejection, Applicant argues:
The Examiner alleges that Nathan teaches a fixed dose in which the weight to weight ratio of anti-CTLA4:anti-PD1 ratio can be 1:2, or 1:3 or 1:4 ([0055]), and that one of ordinary skill would adjust ratio to achieve desired therapeutic effects based on pharmacokinetic factors. However, in contrast to Applicant's claimed invention, Nathan merely discloses ratios for pharmaceutical compositions where antibodies are combined after production by mutually exclusive cells, not ratios where both antibodies are produced by a single cell line, as required by Applicant’s claims. The Examiner's citation to Nathan paragraph [0055] discusses fixed doses in compositions for administration, not the advantageous production of the claimed I :2 ratio of antihCTLA4:anti-hPD l from a single CHO cell, as required by Applicant's claims. Thus, it is respectfully submitted that Sound Biologics News in further view of Yan and Nathan, alone or in combination, fail to make out a prima facie case of obviousness.
Applicant’s arguments have been fully considered but they are not persuasive. Although Nathan does not teach to make the antibody mixture with a ratio of 1:2 in a single CHO cell, Yan teaches a method of making a mixture of antibodies, comprising the steps of: (a) culturing the host cell (such as CHO cell) line expressing the mixture of antibodies in a culture medium, and (b) recovering the mixture of antibodies from the cell mass or the culture medium. Yan teaches method of making a mixture of anti-PD-1 and anti-CTLA4 antibodies. As set forth above, one ordinary skill in the art would have been motivated to produce the nucleic acid encoding the antibodies, because Yan teaches that the isolation of the nucleic acid can be used to produce the mixture of antibodies with a proper vector and host cells and given that Yan teaches that the mixture of antibodies that target more than one antigen or epitope can be more effective.
Furthermore, as evidenced by Nguyen (a new reference), the method of regulating protein expression has been well known in the art. One of ordinary skill in the art would have reasonable expectation of success to modify the ratio of anti-CTLA4 antibody and anti-PD1 antibody produced in CHO cells to 1:2 for better therapeutic properties, as taught by Nathan.
Thus, the claims are properly rejected by the new rejection set forth above.
Conclusion
No claims are allowed.
All other objections and rejections set forth in the previous Office Action of 08/12/2025 are hereby withdrawn in view of the claim amendments and Applicants’ arguments.
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/CHENG LU/Examiner, Art Unit 1642