DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 7, 2026, has been entered.
Previous Rejections
Applicant’s arguments, filed April 7, 2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 23, 2026, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Applicant cannot rely upon the certified copy of the foreign priority application (dated August 2019) to overcome the 35 U.S.C. 103 rejection over Rinaldi (US 2018/0369377 A1, published December 2018, prior art under 102(a)(1))) in view of Bailey (US 2022/0000858 A1, filed November 2019, prior art under 102(a)(2)) because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Claim Status
Claims 1, 2, 4, 7, 8, 38, 39, 48, 52, 53, 77, 78, 80, 82, 84, 85, 87, 88, 91, 93, 95, 96, 98, and 105-111 are pending.
Claims 77, 78, 80, 82, 84, 85, 87, 88, 91, 93, 95, 96, 98, and 105 – 111 are withdrawn.
Claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53 are examined here-in.
Claim Objections
Claim 48 is objected to because of the following informalities:
In claim 48, the concentrations recited are only in units of mg, which appears to be a typographical error. If appropriate, units should be corrected to mg/mL.
Appropriate correction is required.
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 non-obviousness.
Claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53 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, 0063 – 0064, 0073 – 0074), and suggests that these active ingredients can be used in similar formulations or according to similar methods.
Claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53 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-PD-L1 (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 (paragraphs 0065 – 0070) reads on instant claims 1, 2, 4, 7, 8, 38, 39, and 48.
Rinaldi’s teaching for an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody (paragraphs 0065 – 0066) overlaps on the instantly claimed range of antibody from 15 to 40 mg/mL as recited in claim 1, and an amount of 20 mg/mL as recited in claims 2, 38, 38, and 48. Claimed ranges or amounts that fall within or 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 as a stabilizer, which converts to approximately 90 to 121 mg/mL trehalose dihydrate (paragraph 0068) overlaps on the instantly claimed range of 80 to 110 mg/mL as recited in claim 1 and an amount of 100 mg/mL as recited in claims 4, 38, 39, and 48.
Rinaldi’s teaching for 5 to 15 mM acetate as buffering agent, which converts to approximately 0.68 to 2.05 mg/mL sodium acetate trihydrate (paragraph 0067), overlaps on the claimed range of 0.2 to 2.5 mg/mL as recited in claim 1, the claimed range of 1.7 to 1.8 mg/mL as recited in claim 38, and an amount of 1.742 mg/mL as recited in claims 7, 39, and 48.
Rinaldi’s teaching that the formulation has a pH of 5.0 to 5.6 (paragraphs 0065 – 0070) overlaps on the claimed pH range of 4.5 to 5.5 as recited in claim 1 and pH 5.0 as recited in claims 8, 38, 39, and 48. Rinaldi teaches that the conjugate acid is used for titrating a buffer system and that acetic acid is conjugate to acetate (paragraphs 0052 – 0054), therefore a person of ordinary skill in the art would recognize acetic acid as the conjugate acid to titrate the formulation to the desired pH.
As discussed above, Rinaldi’s teaching for an aqueous pharmaceutical antibody formulation with 1 to 30 mg/mL antibody (paragraphs 0065 – 0066) overlaps on the instantly claimed range of antibody from 15 to 40 mg/mL as recited in claim 1, and an amount of 20 mg/mL as recited in claims 2, 38, 38, and 48. 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 that the aqueous pharmaceutical formulation is parenterally administered via subcutaneous, intramuscular, or intravenous injection (paragraph 0197) reads on instant claims 52 and 53.
Examiner’s Reply to Attorney Arguments Dated April 7, 2026
Applicant argues that the claimed subject matter differs from Rinaldi because Rinaldi contains a different antibody and includes a surfactant (Remarks page 11). As an initial matter, the rejection was not made over Rinaldi alone, but over the combination of Rinaldi and Bailey. According to MPEP 2145(iv), one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. The 35 U.S.C. 103 rejection of claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53 is over Rinaldi in view of Bailey, therefore one cannot show non-obviousness by attacking references individually. Although this argument (and the following arguments) appears to be against the teachings of one reference individually, and one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references according MPEP 2145(iv) the Examiner will address each in arguendo for the sake of compact prosecution. Although Rinaldi teaches a different antibody (avelumab), with consideration to Bailey’s teachings 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-PD-L1 (paragraph 0073).
Applicant argues that prolgolimab and avelumab have different amino acid sequences and targets, and that “the skilled person would readily appreciate that even a single amino acid substitution in the CDR leads to dramatic changes in antibody activity” referencing sources cited in the previous reply (Remarks pages 11 and 12). First, any changes in antibody activity due to differences in the primary sequence of the antibodies is not being argued by the Examiner: the Examiner agrees that any changes in protein sequence generally have effects on protein activity. However, the substitution of prolgolimab for avelumab is considered simple substitution of one known element for another to obtain predictable results in the context of a stable formulation. In other words, a person of ordinary skill in the art would expect general formulation ingredients to be effective for prolgolimab. In arguendo, common ingredients for stabilizing protein formulations are known. As evidenced by Capelle (Cappelle, M.A.H., et al. “High throughput screening of protein formulation stability: practical considerations” European Journal of Pharmaceutics and Biopharmaceutics 65 (2007), p. 131 – 148), although there is no single composition or combination of ingredients that reliably stabilizes every protein (page 132 column 2), there are many commonly used ingredients that effectively stabilize most proteins (page 133 column 2, Table 1). Capelle’s Table 1 includes commonly used buffers, sugars, surfactants, and other ingredients for stabilizing protein formulations, including acetate buffer and trehalose as claimed (page 134). This evidence supports the Examiner’s previous reasoning, that a person of ordinary skill in the art would have a reasonable expectation of success substituting prolgolimab for avelumab in the composition taught by Rinaldi, because Bailey teaches that prolgolimab and avelumab are both anti-cancer agent checkpoint inhibitors (paragraphs 0025, 0073 – 0074) and thus would be expected to be stabilized by similar formulations. Therefore, the substitution of prolgolimab for avelumab is prima facie obvious as simple substitution of one known element for another to obtain predictable results (MPEP 2143(i)(b)).
Applicant argues that the claimed subject matter has been developed for the antibody prolgolimab specifically rather than as a method for the treatment of cancer (Remarks page 12). According to MPEP 2144(iv) rationale different from Applicant’s is permissible “it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant”, as such, Applicant’s rationale does not patently distinguish the claimed composition over the prior art, because the prior art combination of Rinaldi and Bailey teaches each of the claimed elements, and simple substitution of one element for another is prima facie obvious according to MPEP 2143(i)(b).
Applicant alleges “an unexpected selection of qualitative and quantitative composition of excipients that ensures the stability of prolgolimab aqueous compositions in a wide range of concentrations was performed” (Remarks page 12). The Examiner disagrees because each of the claimed ingredients is taught in claimed amounts in the prior art, as discussed in detail in the body of the rejection above.
Applicant argues that a composition for an antibody to treat a first type of cancer cannot necessarily be used for an antibody to treat another cancer (Remarks page 12). As discussed above, any changes in antibody activity due to differences in the primary sequence of the antibodies is not being argued by the Examiner: the Examiner agrees that any changes in protein sequence generally have effects on protein activity. The Examiner is also not asserting that the substituting one antibody for another will be effective for treating different cancers. Based on the teachings of Rinaldi and Bailey, the substitution of prolgolimab for avelumab appears to be simple substitution of one known element for another to obtain predictable results in the context of a stable formulation. In other words, a person of ordinary skill in the art would expect general formulation ingredients to be effective for prolgolimab. Cappelle’s teachings, as discussed above, establish that although there is no single composition or combination of ingredients that reliably stabilize every protein (page 132 column 2), there are many commonly used ingredients that effectively stabilize most proteins (page 133 column 2, Table 1). Capelle’s Table 1 includes commonly used buffers, sugars, surfactants, and other ingredients for stabilizing protein formulations, including acetate buffer and trehalose as claimed (page 134). This evidence supports the Examiner’s argument that a person of ordinary skill in the art would have a reasonable expectation of success substituting prolgolimab for avelumab in the composition taught by Rinaldi, because Bailey teaches that prolgolimab and avelumab are both anti-cancer agent checkpoint inhibitors (paragraphs 0025, 0073 – 0074) and thus would be expected to be stabilized by similar formulations.
Applicant appears to argue that the instantly claimed subject matter is distinct from the prior art because the instant claims require an acetate-buffer and trehalose, whereas some examples in the prior art also include surfactant (Remarks pages 13 – 14, e.g. “only the presence of all these excipients and in the presence of surfactants ensures the stability of avelumab as disclosed by Bailey”; “in the claimed subject matter, the stability of prolgolimab is provided by a combination of two excipients: acetate buffer and trehalose” and “Bailey does not indicate that an acetate-based buffer in combination with trehalose can be used to prepare a stable antibody composition without a surfactant”). The Examiner disagrees, because according to MPEP 2111.03(i), the transitional term “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements. Therefore, as written, independent claim 1 does not exclude surfactants or other additives.
Claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Li (US 2018/0339045 A1) in view of Ekimova (US 2019/0127478 A1).
Li teaches a stable anti-PD-1 antibody preparation comprising an anti-PD-1 antibody, a buffer, and a stabilizer that effectively suppresses antibody aggregation and deamidation, preventing degradation and resulting in a stable formulation (abstract, paragraphs 0005 – 0006).
Li teaches the concentration of anti-PD-1 antibody is in a range of 1 to 60 mg/mL (paragraph 0014).
Li teaches the buffer is an acetate buffer in a concentration of 1 to 50 mM (paragraph 0015).
Li teaches the pH of the formulation is in a range from 4.5 to 6.0 (paragraph 0016).
Li teaches trehalose dihydrate is a preferred stabilizer for the pharmaceutical formulation to be included in an amount of 30 to 120 mg/mL (paragraph 0017).
Li teaches the formulation is an injectable formulation that can be administered intravenously, subcutaneously, or parenterally (paragraphs 0019, 0064).
Li does not teach the anti-PD-1 antibody is prolgolimab.
Ekimova teaches the missing element of Li.
Ekimova teaches an anti-PD-1 antibody according to SEQ ID Nos 9 and 10, which is also known as BCD-100 (paragraphs 0021, 0022, 0043, 0044, 0048 – 0052, 0259, 0272, pages 26 – 28). BCD-100 is also known as prolgolimab. Ekimova teaches the anti-PD-1 antibody BCD-100 increases IL-2 concentration greater than pembrolizumab or nivolumab antibodies administered in the same amount, indicating greater functional activity of BCD-100 relative to pembrolizumab or nivolumab (paragraphs 0006, 0228 – 0232, Figure 6).
Claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53 are prima facie obvious over the combination of Li and Ekimova, 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) 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)). A person of ordinary skill in the art would have been motivated to modify Li’s composition to include BCD-100 antibody as taught by Ekimova because Ekimova teaches BCD-100 has greater activity than other PD-1 antibodies (paragraphs 0228 – 0232). With this modification, a person of ordinary skill in the art would expect the formulation to be stabilizing for BCD-100 antibody, which illustrates greater activity than other anti-PD-1 antibodies, therefore, this combination of known elements would be expected to yield predictable results, which is prima facie obvious according to MPEP 2143(i)(a).
Li’s teaching for a stable anti-PD-1 antibody preparation comprising an anti-PD-1 antibody, a buffer, and a stabilizer that effectively suppresses antibody aggregation and deamidation, preventing degradation and resulting in a stable formulation (abstract, paragraphs 0005 – 0006), in combination with Ekimova’s teaching for BCD-100 as an anti-PD-1 antibody (paragraphs 0006, 0021, 0022, 0043, 0044, 0048 – 0052, 0228 – 0232, 0259, 0272, Figure 6, pages 26 – 28) reads on instant claims 1, 2, 4, 7, 8, 38, 39, 48, 52, and 53. As discussed above, a person of ordinary skill in the art would have been motivated to modify Li’s composition to include BCD-100 antibody as taught by Ekimova because Ekimova teaches BCD-100 has greater activity than other PD-1 antibodies (paragraphs 0228 – 0232).
Li’s teaching that the concentration of anti-PD-1 antibody is in a range of 1 to 60 mg/mL (paragraph 0014) overlaps on the instantly claimed range of antibody from 15 to 40 mg/mL as recited in claim 1, and an amount of 20 mg/mL as recited in claims 2, 38, 38, and 48. Claimed ranges or amounts that fall within or overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Li’s teaching that the buffer is an acetate buffer in a concentration of 1 to 50 mM (paragraph 0015) which converts to approximately 0.14 to 6.8 mg/mL, overlaps on the claimed range of 0.2 to 2.5 mg/mL as recited in claim 1, the claimed range of 1.7 to 1.8 mg/mL as recited in claim 38, and an amount of 1.742 mg/mL as recited in claims 7, 39, and 48.
Li teaches the pH of the formulation is in a range from 4.5 to 6.0 (paragraph 0016) overlaps on the claimed pH range of 4.5 to 5.5 as recited in claim 1 and pH 5.0 as recited in claims 8, 38, 39, and 48. Although LI does not explicitly teach acetic acid for titrating the buffer to the desired pH, a person of ordinary skill in the art would recognize that acetic acid is the conjugate acid to acetate buffer, and be motivated to use the conjugate acid to titrate the formulation to the desired pH.
Li’s teaching that trehalose dihydrate is a preferred stabilizer to be included in an amount of 30 to 120 mg/mL (paragraph 0017) overlaps on the instantly claimed range of 80 to 110 mg/mL as recited in claim 1 and an amount of 100 mg/mL as recited in claims 4, 38, 39, and 48.
Li’s teaching that the formulation is an injectable formulation that can be administered intravenously, subcutaneously, or parenterally (paragraphs 0019, 0064) reads on instant claims 52 and 53.
Conclusion
All claims are rejected. No claims are allowed.
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
