DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed November 25, 2025 have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 77, 78, 80, 82, 84, 85, 87, 88, 91, 93, 95, 96, 98, and 105 – 111 are withdrawn.
Claims 1 – 5, 7, 8, 18 – 23, 28 – 33, 37 – 39, 43, 44, 48 – 53, and 99 – 104 are examined here-in.
Claim Rejections - 35 USC § 103 (Maintained)
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 non-obviousness.
Claims 1 – 5, 7, 8, 18 – 23, 28 – 33, 37 – 39, 43, 44, 48 – 53, and 100 – 104 are rejected under 35 U.S.C. 103 as being unpatentable over Rinaldi (US 2018/0369377 A1, of record) in view of Bailey (US 2022/0000858 A1, of record).
Rinaldi teaches an aqueous pharmaceutical formulation of anti-PD-L1 antibody (abstract). The formulation of Rinaldi has 1 to 30 mg/mL antibody, which meets subsection I) within claim 1.
Rinaldi teaches the aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody, 5 to 15 mM acetate as buffering agent, 240 to 320 mM trehalose as a stabilizer, and 0.25 to 0.75 mg/mL surfactant, where the formulation has a pH from 5.0 to 5.6 (paragraph 0065). According to calculations by the Examiner, an acetate concentration of 5 to 15 mM is equal to 0.68 to 2.05 mg/mL sodium acetate trihydrate and a trehalose concentration of 240 to 320 mM is equal to 90 to 121 mg/mL trehalose dihydrate.
Rinaldi teaches histidine as a buffer or stabilizer in a concentration of 5 to 15 mM (paragraphs 0052, 0055, 0067). According to calculations by the Examiner, histidine in the range of 5 to 15 mM is equal to 0.78 to 2.3 mg/mL.
Rinaldi teaches poloxamer 188 as a surfactant in a concentration of 0.35 to 0.75 mg/mL (paragraph 0069, 0075, 0079, 0084, 0090, 0095, 0119, 0125, 0131, 0155, 0163, Table 3). Rinaldi teaches that the inclusion of a surfactant improves antibody stability (paragraph 0293, 0301).
Rinaldi teaches that the aqueous pharmaceutical formulation is parenterally administered via subcutaneous, intramuscular, or intravenous injection (paragraph 0197).
Rinaldi does not teach the antibody is prolgolimab.
Bailey teaches that avelumab and prolgolimab are both anti-cancer agent checkpoint inhibitors (paragraphs 0025, 0073 – 0074).
Claims 1 – 5, 7, 8, 18 – 23, 28 – 33, 37 – 39, 43, 44, 48 – 53, and 100 – 104 are prima facie obvious over the combination of Rinaldi and Bailey, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., antibody, stabilizer, buffer, surfactant) were known in the prior art (e.g., immunotherapy) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results (e.g., an aqueous pharmaceutical formulation) to one of ordinary skill in the art (MPEP 2143(I)(a)). Although Rinaldi teaches avelumab as the antibody, the substitution for the instantly claimed prolgolimab is prima facie obvious as simple substitution of one known element for another to obtain predictable results (MPEP 2143(I)(b)). A person of ordinary skill in the art would be motivated to substitute prolgolimab for avelumab because Bailey teaches that avelumab (as taught by Rinaldi) and prolgolimab are both anti-cancer agent checkpoint inhibitors (paragraphs 0025, 0073 – 0074). Furthermore, a person of ordinary skill in the art would have been motivated to substitute prolgolimab for avelumab to target anti-PD1 rather than anti-PDL1 (paragraph 0073).
Said differently, the substitution for prolgolimab (as taught by Bailey) into the formulation taught by Rinaldi (which includes avelumab, trehalose, sodium acetate, and acetic acid) is prima facie obvious because all of the claimed components are known and function according to known methods to yield predictable results (MPEP 2143(i)(a) and (b)). A person or ordinary skill in the art would expect the substitution of prolgolimab for avelumab to yield predicable results (regarding buffer and formulation stability) because Bailey teaches these antibodies are both commonly used to treat cancer (paragraphs 0025, 0073 – 0074). Furthermore, a person of ordinary skill in the art would have the necessary expertise to recognize that because prolgolimab is an anti-PD-1 antibody and avelumab is an anti-PD-L1 antibody, the substitution of one antibody in the buffer formulation for another would necessarily result in a different treatment mechanism, i.e. treating a cancer disease in a different way.
Rinaldi’s teaching for an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody, 240 to 320 mM trehalose as a stabilizer (90 to 121 mg/mL trehalose dihydrate), and 5 to 15 mM acetate as buffering agent (0.68 to 2.05 mg/mL sodium acetate trihydrate), where the formulation has a pH from 5.0 to 5.6 (paragraph 0065) reads on instant claims 1 – 5, 7, 8, 37 – 39, and 48.
Rinaldi’s teaching for an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody, 240 to 320 mM trehalose as a stabilizer (90 to 121 mg/mL trehalose dihydrate), and 5 to 15 mM histidine (0.78 to 2.3 mg/mL), where the formulation has a pH from 5.0 to 5.6 (paragraphs 0052, 0055, 0065, 0067) reads on instant claims 18 – 23, 28 – 33, 43, and 44.
Rinaldi’s teaching for 1 to 30 mg/mL antibody (paragraph 0065) overlaps on the claimed amounts of 5 to 150 mg/mL, 15 to 40 mg/mL, 15 to 25 mg/mL, and 20 mg/mL as recited in instant claims 1 – 4, 8, 18 – 21, 37 – 39, 43, 44, and 48. Claimed ranges that overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(I). A person of ordinary skill in the art would have been motivated to use prolgolimab as antibody rather than avelumab because Bailey teaches that avelumab (as taught by Rinaldi) and prolgolimab are both anti-cancer agent checkpoint inhibitors (paragraphs 0025, 0073 – 0074). Furthermore, a person of ordinary skill in the art would have been motivated to substitute prolgolimab for avelumab to target anti-PD1 rather than anti-PDL1 (paragraph 0073). Substitution of one known element for another is prima facie obvious according to MPEP 2143(I)(b).
Rinaldi’s teaching for 240 to 320 mM trehalose (90 to 121 mg/mL trehalose dihydrate) (paragraph 0065) overlaps on the claimed amounts of 70 to 110 mg/mL, 80 to 110 mg/mL, 95 to 105 mg/mL, 80 to 110 mg/mL, 80 mg/mL, and 100 mg/mL for claims 1, 3, 4, 8, 18, 22, 23, 37 – 39, 44, and 48.
Rinaldi’s teaching 5 to 15 mM acetate as buffering agent (0.68 to 2.05 mg/mL sodium acetate trihydrate) (paragraph 0065) overlaps on the claimed amounts of 0.2 to 2.5, 1.6 to 1.9, 1.7 to 1.8 mg/mL, and 1.742 mg/mL as recited in instant claims 1, 5, 7, 37 – 39, and 48.
Rinaldi’s teaching 5 to 15 mM and 5 to 15 mM histidine (0.78 to 2.3 mg/mL) (paragraphs 0052, 0055, 0067) overlaps on the claimed amounts of 0.2 to 2.5 mg/mL, 0.7 to 1.0 mg/mL, and 00.92 mg/mL as recited in instant claims 18, 28, 29, 43, and 44.
Rinaldi’s teachings for a pH from 5.0 to 5.6 (paragraph 0065) overlaps on the claimed amounts of 4.5 to 5.5, 5.0 to 5.5, 5.5 to 6.5, 5.0, and 5.5 as recited in instant claims 1, 8, 37 – 39, 43, 44, and 48.
Rinaldi’s teaching to include poloxamer 188 as a surfactant in the composition, where the surfactant improves antibody stability (paragraph 0069, 0075, 0079, 0084, 0090, 0095, 0119, 0125, 0131, 0155, 0163, 0293, 0301, Table 3) reads on instant claims 49, 50, 100, and 101 which recite the inclusion of a solubilizer. The instant specification describes a solubilizer as a pharmaceutically acceptable non-ionic surfactant (paragraph 0036), therefore, Rinaldi’s teaching of poloxamer 188 as a surfactant reads on the instant claims.
Rinaldi’s teaching for poloxamer 188 in a concentration of 0.35 to 0.75 mg/mL (paragraph 0069, 0075, 0079, 0084, 0090, 0095, 0119, 0125, 0131, 0155, 0163, Table 3) overlaps on the instantly claimed range of 0 to 1 mg/mL as recited in claims 51 and 102.
Rinaldi’s teaching that the aqueous pharmaceutical formulation is parenterally administered via subcutaneous, intramuscular, or intravenous injection (paragraph 0197) reads on instant claims 52, 53, 103, and 104.
Claims 1 – 5, 7, 8, 18 – 23, 28 – 33, 37 – 39, 43, 44, 48 – 53, and 99 - 104 are rejected under 35 U.S.C. 103 as being unpatentable over Rinaldi (as cited above), Bailey (as cited above), and further in view of Fraunhofer (US 2012/0263731 A1, of record).
The combination of Rinaldi and Bailey is discussed above. As discussed above, Rinaldi teaches an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody, which meets subsection I) within claim 1. It does not, however, teach higher concentrations of antibody, such as 90 to 150 mg/mL as recited in clause II of claim 1.
Accordingly, the combination Rinaldi and Bailey differs from clause II of applicant’s claim 1 in not teaching higher concentrations of antibody, such as 90 to 150 mg/mL as recited in instant claim 1.
Fraunhofer teaches the missing element of the combination of Rinaldi and Bailey necessary to render clause II of applicant’s claim 1 obvious.
Fraunhofer teaches an aqueous pharmaceutical formulation with antibody in the amount of 50, 75, and 100 mg/mL or more (paragraph 0016). Fraunhofer teaches that a high concentration of antibody is advantageous because it can impact the mode and frequency of drug administration to the subject (paragraph 0003).
Claims 1 – 5, 7, 8, 18 – 23, 28 – 33, 37 – 39, 43, 44, 48 – 53, and 99 - 104 are prima facie obvious over the combination of Rinaldi, Bailey, and Fraunhofer because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. A person of ordinary skill in the art would be motivated modify the combination of Rinaldi and Bailey to include a high concentration of antibody as taught by Fraunhofer because Fraunhofer teaches that a high concentration of antibody is advantageous to modulate mode and frequency of administration (paragraph 0003).
Rinaldi’s teaching for an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody, 240 to 320 mM trehalose as a stabilizer (90 to 121 mg/mL trehalose dihydrate), and 5 to 15 mM acetate as buffering agent (0.68 to 2.05 mg/mL sodium acetate trihydrate), where the formulation has a pH from 5.0 to 5.6 (paragraph 0065) in combination with Fraunhofer’s teaching to include an antibody in a concentration of 50, 75, and 100 mg/mL or more (paragraph 0016) reads on instant claims 1 – 5, 7, 8, 37 – 39, and 48. A person of ordinary skill in the art would have been motivated to include the antibody in a high concentration as taught by Fraunhofer because a high concentration of therapeutic agent enables flexibility with administration mode and frequency (paragraph 0003).
A person of ordinary skill in the art would have been motivated to use prolgolimab as antibody rather than avelumab because Bailey teaches that avelumab (as taught by Rinaldi) and prolgolimab are both anti-cancer agent checkpoint inhibitors (paragraphs 0025, 0073 – 0074). Furthermore, a person of ordinary skill in the art would have been motivated to substitute prolgolimab for avelumab to target anti-PD1 rather than anti-PDL1 (paragraph 0073). Substitution of one known element for another is prima facie obvious according to MPEP 2143(I)(b).
Rinaldi’s teaching for an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody, 240 to 320 mM trehalose as a stabilizer (90 to 121 mg/mL trehalose dihydrate), and 5 to 15 mM histidine (0.78 to 2.3 mg/mL), where the formulation has a pH from 5.0 to 5.6 (paragraphs 0052, 0055, 0065, 0067) in combination with Fraunhofer’s teaching to include an antibody in a concentration of 50, 75, and 100 mg/mL or more (paragraph 0016) reads on instant claims 18 – 23, 28 – 33, 43, and 44.
Fraunhofer’s teaching to include an antibody in a concentration of 50, 75, and 100 mg/mL or more (paragraph 0016) overlaps on the claimed amounts of 5 to 150 mg/mL, 90 to 110 mg/mL, 90 to 150 mg/mL, and 100 mg/mL as recited in instant claims 1 – 4, 8, 18 – 21, 37 – 39, 43, 44, 48, and 99. Claimed ranges that overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(I).
Rinaldi’s teaching for 240 to 320 mM trehalose (90 to 121 mg/mL trehalose dihydrate) (paragraph 0065) overlaps on the claimed amounts of 50 to 110 mg/mL, and is approaching the claimed amounts 75 to 85 mg/mL, 80 mg/mL for claims 1, 3, 4, 8, 18, 22, 23, 37 – 39, 44, and 48. Claimed ranges that are approaching ranges taught by the prior art are prima facie obvious absent any showing of criticality (MPEP 2144.05(I)).
Rinaldi’s teaching 5 to 15 mM acetate as buffering agent (0.68 to 2.05 mg/mL sodium acetate trihydrate) (paragraph 0065) overlaps on the claimed amounts of 0.2 to 2.5, 1.6 to 1.9, 1.7 to 1.8 mg/mL, and 1.742 mg/mL as recited in instant claims 1, 5, 7, 37 – 39, and 48.
Rinaldi’s teaching 5 to 15 mM and 5 to 15 mM histidine (0.78 to 2.3 mg/mL) (paragraphs 0052, 0055, 0067) overlaps on the claimed amounts of 0.2 to 2.5 mg/mL, 0.7 to 1.0 mg/mL, and 00.92 mg/mL as recited in instant claims 18, 28, 29, 43, and 44.
Rinaldi’s teachings for a pH from 5.0 to 5.6 (paragraph 0065) overlaps on the claimed amounts of 4.5 to 5.5, 5.0 to 5.5, 5.5 to 6.5, 5.0, and 5.5 as recited in instant claims 1, 8, 37 – 39, 43, 44, and 48.
Rinaldi’s teaching to include poloxamer 188 as a surfactant in the composition, where the surfactant improves antibody stability (paragraph 0069, 0075, 0079, 0084, 0090, 0095, 0119, 0125, 0131, 0155, 0163, 0293, 0301, Table 3) reads on instant claims 49, 50, 100, and 101 which recite the inclusion of a solubilizer. The instant specification describes a solubilizer as a pharmaceutically acceptable non-ionic surfactant (paragraph 0036), therefore, Rinaldi’s teaching of poloxamer 188 as a surfactant reads on the instant claims.
Rinaldi’s teaching for poloxamer 188 in a concentration of 0.35 to 0.75 mg/mL (paragraph 0069, 0075, 0079, 0084, 0090, 0095, 0119, 0125, 0131, 0155, 0163, Table 3) overlaps on the instantly claimed range of 0 to 1 mg/mL as recited in claim 51 and 102.
Rinaldi’s teaching that the aqueous pharmaceutical formulation is parenterally administered via subcutaneous, intramuscular, or intravenous injection (paragraph 0197) reads on instant claims 52, 53, 103, and 104.
Examiner’s Reply to Attorney Arguments Dated November 25, 2025
Applicant argues that because prolgolimab binds to PD-1 and avelumab binds to PD-L1, the antibodies have different properties, different mechanisms of action, structure, and toxicity, and thus they cannot be directly compared or considered to be interchangeable (Remarks page 15). The Examiner would like to emphasize that the substitution of one antibody for another for the purposes of treating a specific disease was not the argument made. Rather, Rinaldi teaches the antibody avelumab with the claimed formulation components of trehalose dihydrate, sodium acetate, and acetic acid in the claimed amounts, and a person of ordinary skill in the art would have a reasonable expectation of success using prolgolimab rather than avelumab because Bailey teaches both avelumab and prolgolimab are antibodies for cancer treatment. As noted in the body of the rejection above, the substitution of prolgolimab for avelumab would result in targeting PD-1 rather than PD-L1.
Applicant argues that Rinaldi does not provide any examples of a formulation comprising prolgolimab (Remarks page 17). First, the Examiner notes that the teachings of the prior art are not limited to the examples, but include the full disclosure of the prior art reference, including nonpreferred and alternative embodiments, according to MPEP 2123. Second, the rejection was not made over Rinaldi alone, rather the teachings of Bailey were relied upon for prolgolimab.
Applicant argues that Fraunhofer discloses formulations comprising anti-TNFa antibody, while prolgolimab is an anti-PD-1 antibody and therefore because the antibodies have different targets they cannot be substituted (Remarks page 17). Applicant argues “it is incorrect to compare the compositions of antibodies against PD-1 and TNFa with each other from the point of view of pharmacology and mechanism of action, since these antibodies differ not only in target, physiological effects, but also in chemical and biopharmaceutical composition” (Remarks page 18). As discussed with regards to the combination of Rinaldi and Bailey, the Examiner would like to emphasize that the substitution of one antibody for another for the purposes of treating a specific disease was not the argument made.
In the case of Rinaldi, Bailey, and Fraunhofer, a person of ordinary skill in the art would anticipate substitution of prolgolimab into Rinaldi’s composition in the amounts taught by Fraunhofer to have a reasonable expectation of success because:
Rinaldi teaches the antibody avelumab with the claimed formulation components of trehalose dihydrate, sodium acetate, and acetic acid in the claimed amounts;
Bailey teaches both avelumab and prolgolimab are antibodies for cancer treatment, therefore a person of ordinary skill in the art would expect that the substitution of prolgolimab for avelumab in Rinaldi’s formulation would yield predictable results;
Fraunhofer teaches an aqueous pharmaceutical formulation with antibody in the amount of 50, 75, and 100 mg/mL or more (paragraph 0016). Fraunhofer teaches that a high concentration of antibody is advantageous because it can impact the mode and frequency of drug administration to the subject (paragraph 0003).
Therefore, a person of ordinary skill in the art would expect the substitution of prolgolimab for avelumab in the formulation of Rinaldi, in elevated amounts taught by Fraunhofer to have reasonable success. Furthermore, a person of ordinary skill in the art would be motivated to use the high concentrations of antibody as taught by Fraunhofer in the composition of Rinaldi as modified by Bailey because Fraunhofer teaches higher concentration of antibody impacts the mode and frequency of drug administration.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Toriana N. Vigil whose telephone number is (571)270-7549. The examiner can normally be reached Monday - Friday 9:00 a.m. - 5:00 p.m. EST.
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/TORIANA N. VIGIL/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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