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 .
Response to Amendment
The Amendment filed August 6, 2025 in response to the non-final rejection of May 8, 2025 is acknowledged and has been entered.
Claims 1-4, 6, 8, 19-21, 24-27 were amended or previously presented. Claims 28-34 were newly added.
Claims 1-4, 6, 8, 19-21, and 24-34 are currently under consideration.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Priority
Receipt is acknowledged of the English translation (filed 08/06/2025) of the certified Chinese priority application No. 201910249953.4.
Specification
The objections to the specification in the non-final mailed 05/08/2025 (pages 2-3) are withdrawn in view of applicant’s amendments.
Rejections Withdrawn
The rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter in the action mailed 05/08/2025 (pages 3-4) are withdrawn in view of applicant’s amendments.
Rejections Maintained
Claim(s) 1-4, 6, 8, 19-21 and 24-27 remain rejected and new claims 28-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ying et al WO 2019/062831 (priority to 9/29/2017) or Ying et al US 11,365,247 (priority to 9/29/2017) in view of Leach et al WO 2015/061584, Blake-Haskins et al WO 2015/173782 and Sharma et al WO 2018/204368 (PTO-892) for the reasons of record and for the reasons set forth herein.
Claim(s) 1-4, 6, 8, 19 and 24-26 remain rejected and new claims 28-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ying et al WO 2020/114478 (priority to 12/7/2018) or Ying et al US 12,258,405 (priority to 12/7/2018) in view of Leach et al WO 2015/061584, Blake-Haskins et al WO 2015/173782 and Sharma et al WO 2018/204368 for the reasons of record and for the reasons set forth herein.
New claims 28-34 were earlier presented. However, because of the indefinite language associated with “preferably” they were amended and presented as new claims. However, the limitations were previously addressed in the non-final rejection.
All Ying references rely upon their earliest effective filing dates and thus are considered 102(a)(2) dates.
Applicants attempt to invoke the 102(b)(2)(c) exception (Remarks, 08/06/2025, page 9) by stating that: Applicant submits that Ying '247 and Ying ‘405 share common ownership (Jiangsu Hengrui Medicine Co., Ltd. and Shanghai Hengrui Pharmaceutical Co., Ltd.) with the present application, and were published after the priority date of the application. Therefore, Ying '247 and Ying ‘405 cannot constitute prior art and cannot be used to evaluate the patentability of the instant claims as the 102(b)(2)(c) exception applies.
This statement has been considered and is not found persuasive. In order to invoke common ownership to except a disclosure as prior art, the applicant (or the patent owner) must provide a statement that the disclosure of the subject matter on which the rejection is based and the claimed invention were owned by the same person or subject to an obligation of assignment to the same person not later than the effective filing date of the claimed invention. See MPEP 717.02(a). Thus, applicants’ statement is defective because it is missing the ‘commonly owned or subject to an obligation of assignment to the same person not later than the effective filing date of the claimed invention’ statement.
Regarding the obviousness aspect, Applicants argue (Remarks, 08/06/2025, page 10) that the cited references fail to teach or suggest each and every element of the claimed invention including defined buffer and surfactant at specified concentration ranges and that each of Blake-Haskins, Leach, and Sharma fail to teach the claimed antibody sequences. They argue that each of the cited references are directed to antibody formulations comprising targets other than IL-5 and the structures of the antibody sequences are different from the anti-IL5 antibody of the present application. Finally, applicants argue that each of Leach, Blake-Haskins, and Sharma fail to provide technical guidance that the claimed anti-IL-5 antibody would remain stable in acetic acid-sodium acetate or succinic acid-sodium succinate buffer at pH 5.0-6.5.
Applicants further argue that there is no reasonable expectation of success because those of ordinary skill in the art would readily recognize that differences in antibody sequences result in distinct physical and chemical properties which can affect the constitutions of an antibody formulation.
These arguments have been considered but are not found persuasive. While applicants are correct in that each of Leach, Blake-Haskins, and Sharma are not specific to “anti-IL5 antibody” formulations, they each delineate the processes of arriving at stabilizing structurally similar proteins in that they all are directed to antibodies. Those of skill in the art recognize that high throughput biophysical screening is common and has reduced the time it takes to assess optimized antibody formulations. In this context, each of Leach, Blake-Haskins, and Sharma discussed buffers containing acetate salts. Blake-Haskins and Sharma also discussed succinate buffers. All references discussed employing sucrose as a stabilizer and each reference discussed pHs from as low as 5 to as high as 7. Further, Blake-Haskins and Sharma highlighted the use of the common surfactant polysorbate 80. The examiner discussed their optimization rationale under MPEP 2144.05 and delineated the teachings while also discussing each of the claimed limitations. They also discussed this in the context of Ying et al.’s teachings where it was stated that Ying et al discloses the same antibodies as in applicant’s claims 1, 15 and 18-21 in pharmaceutical compositions comprising buffers, carriers, diluents or excipients and since Leach et al, Blake-Haskins et al and Sharma et al all disclose antibody formulations with varying concentrations of antibody, similar buffers, similar polysorbates, and similar saccharides as claimed it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to form compositions of the anti-IL-5 antibodies of Ying et al using any of the concentrations of the secondary references. Moreover, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions to yield stable antibody formulations as claimed.
Applicants also argue that the presently claimed preparations showed “surprisingly improved properties”. As demonstrated in Examples 10-17 of the present application, the pharmaceutical composition of claim 1 shows favorable stability in shaking experiments and in forced degradation experiments at 40 °C. For instance, Example 10 confirms that the change in the purity of the SEC monomer in the preparation was less than 3% after 4 days of shaking, and the change in the purity of SEC monomer was less than 4%, even after 13 days of storage at 40 °C, when preparations are conventionally stored at 4 °C. These results clearly demonstrate that the preparation of the present application has surprisingly high stability.
This argument has been considered but is not found persuasive. A review of the experimental protocols [0238-0251] did not reveal anything other than routine optimization by subjecting various buffered samples to common evaluations such as forced degradation, appearance, size exclusion chromatography (SEC), and imaged capillary isoelectric focusing (icIEF). There is no suggestion or teaching that any one preparation provided an unexpected or surprising result. For example, under the stability test of the formulations h1705-008 [0251] the results revealed that SEC, CE (capillary electrophoresis), and IEC (ion exchange chromatography) were slightly decreased but within an “acceptable range”.
Claims 1-4, 6, 8, 19-21 and 24-27 remain rejected and new claims 28-34 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,365,247 and claims 1-13 of US 12,258,394 in view of Leach et al WO 2015/061584, Blake-Haskins et al WO 2015/173782, and Sharma et al WO 2018/204368 (PTO-892) for the reasons of record.
Claims 1-4, 6, 8, 19-21 and 24-27 remain provisionally rejected and new claims 28-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/043,179 (previously and erroneously cited as 18/043,179 as pointed out by applicants) in view of Leach et al WO 2015/061584, Blake-Haskins et al WO 2015/173782 and Sharma et al WO 2018/204368 for the reasons of record.
Applicants argue (Remarks, 08/06/2025, page 6) that the claimed anti-IL-5 antibody formulation is nonobvious relative to the above two patents and one pending application in combination with the prior art of Leach, Blake-Haskins, and Sharma et al. because none of the patents or the pending applications above teach or suggest that the claimed anti-IL-5 antibody would be stable in acetic acid-sodium acetate or succinic acid-sodium succinate buffer at pH 5.0-6.5. This argument has been considered but is not considered persuasive because the teachings of the patents and pending application were not used to arrive at the types of buffers, surfactants, and stabilizers claimed. On the contrary, the previous examiner considered the claims of the patent and the claims of the pending application which recited the same anti-IL-5 antibody structures as currently claimed and not disputed by applicants.
Applicants further argue that none of Leach, Blake-Haskins, and Sharma give technical instruction to obtain a stable anti-IL-5 antibody as claimed in the present application, since differences in the antibody sequences would result in distinct physical and chemical properties, and a formulation suitable to maintain the stability of one protein is not necessarily suitable for another protein. Applicant submits that one of ordinary skill in the art knows that the effects of excipient combinations on a formulation is not predictable.
These arguments have been considered but are not deemed persuasive to remove the obviousness factor. While it is true that differences in antibody sequences may result in different stabilizing formulations the general thrusts of the references were all related to producing stable antibody formulations. Further, high throughput biophysical screening is common and has reduced the time it takes to assess optimized formulations. In this context, each of Leach, Blake-Haskins, and Sharma discussed buffers containing acetate salts. Blake-Haskins and Sharma also discussed succinate buffers. All references discussed employing sucrose as a stabilizer and each reference discussed pHs from as low as 5 to as high as 7. Further, Blake-Haskins and Sharma highlighted the use of the common surfactant polysorbate 80. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions to yield stable antibody formulations as claimed.
In view of the above, applicants’ arguments have not been found persuasive and the rejections are maintained.
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643