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 .
2. Applicant’s amendment filed on 03/23/2023 is acknowledged.
3. Claims 1-12 are pending and under consideration for their full scope.
4. Applicant’s IDS documents filed on 05/05/2023, 08/22/2024 and 09/04/2025.
5. 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.
6. 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.
7. Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over EP 3159007 (IDS filed on 08/22/2024; Reference 1) in view of Ohtake et al. (PTO-892; Reference U) and Zadar et al. (PTO-892; Reference V).
EP 3159007 teaches an anti-fractalkine antibody of SEQ ID NOs 13 and 14; and SEQ ID Nos 11 and 12 wherein the antibody is IgG2 isotype and comprising amino acid substitutions V234A and G237A in the Fc region. (In particular, page 2, lines 44-58). The reference teaches the antibody formulation for subcutaneous administration (page 8, line 34); (further comprising histidine (page 8, line 23); polysorbate 80 (page 8, lines 17-18); further comprising histidine, citrate (citric acid salt), phosphate (phosphoric acid salt), glycine and acetate buffer and phosphate buffered saline which comprises sodium phosphate; and wherein 200 mg of the H3-2L4 anti-fractaline antibody comprising SEQ ID NOs 11 and 12; 13 and 14 is subcutaneously administered (In particular, Example 2)
Instant/reference SEQ ID NO:13 are 100% sequence identical over length and sequence. Instant/reference SEQ ID NO:14 are 100% sequence identical over length and sequence. Instant/ reference SEQ ID NO:11 are 100% sequence identical over length and sequence. Instant/ reference SEQ ID NO:12 are 100% sequence identical over length and sequence.
The claimed invention differs from the prior art in the recitation of a pharmaceutical composition comprising the antibody at a concentration of 200 mg/mL and further comprising 100-400 mM of a basic amino acid selected from the group consisting of arginine, histidine, lysine and ornithine of claim 1; 200-400 mM of the basic amino acid of claim 2; wherein the basic amino acid comprises arginine or histidine of claim 3; wherein the basic amino acid is arginine of claim 4; wherein the arginine is 250mM of claims 5 and 12; and wherein the viscosity is less than 20 cP of claim 10.
Ohtake et al. teaches that high concentration antibody formulations often become too viscous to inject. It takes several minutes to inject a small volume of the formulation, as shown in Fig. 18. Addition of arginine at ≥0.15 M reduced the viscosity, and its inclusion may allow for shorter administration time. Such effect of arginine on high protein concentration formulation may be a viable approach for reducing the formulation viscosity (In particular, page 1065-1068, whole document).
Zidar et al. teaches viscosity presents a major challenge in the formulation development of therapeutic proteins, such as monoclonal antibodies, where highly concentrated protein formulations (protein concentration of over 100 mg/ml) for subcutaneous administration are in great demand as an alternative route to low concentration formulations that are delivered intravenously. Highly concentrated formulations are inherently overly viscous and therefore difficult to inject due to the large force needed to expel them through a needle. Viscosity value of 15 cP is targeted in biopharmacy. Controllably lowering the viscosity of an aqueous protein solution has inherent challenges in a biopharmaceutical setting, where viscosity control is directly linked with potency of the dose. (In particular, pages 309, 313 and 315, whole document).
Zidar et al teaches that the upper protein concentration limit in all liquid biologics of around 200 mg/ml based on the separate quantification of contributions to viscosity. A high portion of steric and hydrodynamic interactions to viscosity as determined from intrinsic viscosity measurements limits the effectiveness of viscosity-reducing additives – even if all residual forces in our system were screened, the maximum achievable concentration would not have significantly exceeded 200 mg/ml. (In particular, page 315, last paragraph, whole document).
Zidar et al teaches that arginine was the most effective viscosity reducing agent among lysine, histidine and arginine and that arginine reduced viscosity by 50%. The reference teaches an equation for determining the reduction in viscosity for given protein and viscosity reducing agent concentration. (In particular, page 313, whole document)
It would have been obvious to one of ordinary skill in the art at the time of invention to have prepared the antibody of EP 3159007 in as concentrated a form as possible for subcutaneous administration given that the dose of antibody required to perform the biological function in vivo was high at 200 mg. As such, it would have been obvious to one of ordinary skill in the art to have prepared a highly concentrate solution for subcutaneous administration . Since highly concentrated formulations are inherently overly viscous and therefore difficult to inject due to the large force needed to expel them through a needle, and because it takes several minutes to inject a small volume of a concentrated antibody formulation, one of ordinary skill in the art would have sought to reduce the viscosity of the solution. As such, it would have been obvious to one of ordinary skill in the art at the time of invention to have looked to the art of Zidar for ways to reduce viscosity of antibody formulations using arginine, lysine and histidine. Since Zidar et al. teaches that arginine had the best viscosity reducing properties it would have been obvious to have preferentially used arginine. It would have been obvious to have used 120 mM arginine, lysine or histidine buffers since that is the concentration used in the viscosity study for antibodies at concentration 150 mg/ml. For higher antibody concentrations it would have been obvious to have increased the arginine, lysine or histidine proportionally with the concentration of the antibody by using the equation presented in the Zidar reference as a guide for selecting the concentrations to obtain optimal viscosity of 15 cP.
It would also have been obvious to one of ordinary skill in the art at the time Applicant's invention was made to determine all operable features of optimal concentrations of the components because as evidence by the art of Zadar, concentration of antibodies and viscosity reducing agents are art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art of manufacturing highly concentrated antibody solutions. The determination of the optimal concentrations of the components is well within the purview of one of ordinary skill in the art at the time the invention was made and lend no patentable import to the claimed invention. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. 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.
8. No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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September 29, 2025
/Nora M Rooney/
Primary Examiner, Art Unit 1641