DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 18-35 and 46 in the reply filed on 12 November 2025 is acknowledged. The requirement is deemed proper and therefore made Final.
Status of Application
Claims 18-31, 33-35 and 46 are pending and subject to examination on the merits.
Priority
The instant application is a 371 of PCT/US2021/049773 filed 10 September 2021 which claims benefit of US provisional application 63/076,600 filed 10 September 2020 is acknowledged. Said document has been received.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12 November 2025 and 08 March 2023 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
It is noted the NPL #3 cited on the IDS of 08 March 2023 is incorrectly cited as “Xinqing et al.”, with Falconer, R.J. as the editor. This is a journal article by Falconer and it is not a book or book chapter. This reference is referenced throughout this office action Falconer. The reference has been lined through on the IDS and provided on the instant PTO-892 which includes the reference again.
Claim Objections
Claim 18 is objected to because of the following informalities: for consistency throughout the claim set, it is suggested to change “antibody IL-23p antibody” in part (i) to “anti-IL-23p antibody”, which is utilized throughout the rest of the claim set. Alternatively, “anti-IL-23p antibody” can be inserted in parenthesis in part (i) after “antibody IL-23p antibody” (e.g. antibody IL-23p antibody (anti-IL-23p antibody)). Appropriate correction is required.
Claims 19-31, 33-35 and 46 are objected to because of the following informalities: each of the claims are ultimately dependent upon claim 18, thus, the preamble in these claims should begin with “The” rather than “A”. Appropriate corrections are required.
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.
Claim(s) 18-31, 33-35 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Beidler et al. teach (US 20140255422 – cited on IDS 03/08/2023) in view of Demarest et al. (US 20190040156 – cited on IDS 03/08/2023) and Falconer (Biotech. Advances, 2019 – cited herein).
Beidler et al. teach the anti-IL-23p antibody mirikizumab comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR) comprising SEQ ID NOs: 7 and 8, respectively, and a light chain (LC) and heavy chain (HC) comprising SEQ ID NO: 9 and 10, respectively, which have 100% sequence identity to instant LCVR and HCVR regions of SEQ ID NO: 7 and 8, respectively, and LC and HC of SEQ ID NOs: 9 and10, respectively (See Supplemental Content, .rapbm files, Results #1), which are formulated with: 1 mg/ml, 50 mg/ml and greater than 100 mg/ml mirikizumab; 10 mM Citrate buffer, pH 6.0, +/- 150 mM NaCl and +/- 0.02% Tween-80 (which is a polysorbate 80). The formulations with the Tween-80 typically had less degradation in all areas tested – See paragraphs 0134-0151.
Beidler et al., however, do not teach mirikisuzmab in a pharmaceutical formulation comprising 3-12 mM Histidine buffer, 25-75 mM NaCl and 2-5% tonicity agent such as mannitol. Nor do they teach formulations comprising mirikisuzmab at concentrations specifically at about 125 mg/ml mg/ml (e.g. claims 24 and 35).
Demarest et al. teach a bispecific antibody that targets TNF-alpha and the p19 subunit of human IL-23 antibody that is formulated at a concentration from 50 to 132 mg/ml concentration and comprising 10 mM histidine buffer, +/- 150mM NaCl, 0.02% polysorbate 80, pH 6.0 and assessed for stability, solubility and viscosity over a 4 week period (See paragraphs 0066-0071). All the formulations demonstrated similar or enhanced stability, solubility and viscosity as compared to other monovalent antibody formulations.
Falconer teach most liquid formulations for therapeutic proteins have a simple formulation comprising: a buffer, tonicity modifier, surfactant, sometimes a stabilizer, the therapeutic protein and water (see Abstract). Further it is taught: “Recent formulations for monoclonal antibodies often use histidine or acetate buffers, sucrose or trehalose as the tonicity modifier and polysorbate 20 or 80 as the surfactant with a pH of 5.7 +/- 0.4.” See Abstract. It is further taught that many therapeutic proteins having greater than 50 mg/ml concentrations, such as monoclonal antibody formulations, provide some buffering capacity by the very nature of the high concentrations. However, additional buffering is needed in many instances (See Section 2.1). Trends in monoclonal antibody formulations include a shift from using phosphate buffers to histidine or acetate buffers which have good buffering capacity at the typical pH needed for antibody formulations of 5.7 +/- 0.4 (See Section 3 and Figure 2); in addition, polysorbate 20 or 80 are utilized as the most common surfactants (See Figure 3); and the most common tonicity agents are sucrose, NaCl followed by trehalose, as well as mannitol, glycerol, sorbitol, amino acids; or combinations of sodium chloride and mannitol; and sodium chloride and sucrose. It can be inferred from Figure 2 that an upward trend in using mannitol or both sodium chloride and mannitol as the tonicity agent is apparent (See Figure 2 and Section 2.2). In addition, they teach how to test each formulation for Stability (six different kinds of stability studies – See Section 6); and testing of critical quality attributes like aggregation, fragmentation etc. (See Section 7).
Therefore it would have been obvious to one of ordinary skill in the art prior the effective filing date of the claimed invention to:
First, substitute histidine buffers as taught in Falconer and Demarest et al. for the citrate buffer of Beidler et al. because Falconer suggest this is the trend in antibody formulations in the recent years (e.g. 2010 and later) and Demarest et al. exemplify the success in using a histidine buffer for an antibody formulation for anti-IL23p. This success and trend would be motivation to one of skill in the art and Demarest et al. further provides the reasonable expectation of success in substituting histidine buffers for citrate buffers. Falconer further provides reasonable expectation of success in this substitution because as they teach, the specific pH of antibody formulations are 5.7 +/- 0.4, where histidine buffers is an especially good buffer at this pH. In addition, it would be obvious to optimize the concentration of the surfactant and the histidine buffer to the optimal concentrations with a reasonable expectation of success in doing so as it is routine in the art and to arrive at concentrations such as 0.3% w/v Tween-80/polysorbate 80 (claims 30 and 33) and 3-12 mM histidine buffer such as 5 mM (claims 25 and 33) (See MPEP 2144.05(II)(A)).
Second, it further would be obvious to utilize a tonicity agent selected from any of those as disclosed in Figure 2 in Falconer and to utilize that in the formulation of Beidler et al. with the histidine buffer as noted above, wherein it would be obvious to utilize either NaCl alone, sucrose alone, trehalose alone, mannitol alone, sorbitol alone, both sodium chloride and mannitol; both sodium chloride and sucrose; or amino acids alone. While there are several tonicity agents to test, each is noted as a potential result effective variable and as such, it would be prudent to test each of the suggested tonicity agents utilized in MAb formulations since 2010 as in Figure 2. This would necessarily arrive at the instant formulation which includes both NaCl and mannitol. As with all formulations, it would be obvious to optimize the particular concentration of the components including both NaCl and mannitol such that one skilled the art would arrive at a concentration between 25-75 mM NaCl, such as 50 mM; and 2-5% mannitol such as 3.3% (claims 18, 31 and 33; and 27 and 33) (See MPEP 2144.05(II)(A)). Furthermore, there would be a reasonable expectation of success in including and using both NaCl and mannitol as the tonicity agent given Falconer report in Figure 2 that there are at least five different therapeutic antibody liquid formulations utilizing them both since 2000, with four of them since 2010.
Third and finally, it would be obvious to optimize the concentration of the antibody formulation of Beidler et al. to include formulations greater than 100 mg/ml, such as 125 mg/ml (claims 24 and 35), which is noted as desirable in paragraph [0135]: “Sufficiently high solubility is desired to enable convenient dosing. For example, a 1 mg/kg dose administered by a 1.0 mL injection into a 100 kg patient will require solubility of 100 mg/mL.” In addition, concentrations greater than 100 mg/ml are possible in paragraph [0136] of Beidler et al., e.g. “Greater than 100 mg/mL solubility is achieved under all three conditions.”. In addition, Demarest exemplify concentrations of the bispecific therapeutic IL-23p19 antibody formulation comprising histidine buffer, NaCl, polysorbate 80 can achieve concentrations of 132mg/ml. Thus, optimizing the concentration of a therapeutic antibody liquid formulation is considered routine optimization of a result effective parameter within the therapeutic liquid monoclonal antibody formulation art (See MPEP 2144.05(II)(A)).
With regard to the limitations in claim 46 and the intended use of the formulation, the intended use does not change the formulation itself. “The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not impart novelty to the claimed product – In re Best 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). M.P.E.P. § 2112(I). Nonetheless, Beidler et al. teach the anti-IL-23p19 antibody mirikizumab is intended for use in treating things such as psoriasis, arthritis, inflammatory bowel diseases etc. (See paragraph 0032).
Conclusion
No claim is allowed.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 07 January 2026