DETAILED ACTION
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 .
Claims 57-59, 61-63, and 65-76 remain pending and examined on the merits.
The Terminal Disclaimer over parent U.S. Patent No. 12,128,090 filed 8/27/25 has overcome the obviousness double patenting rejection previously of record.
Applicant is invited to schedule an interview to advance prosecution on the merits.
Terminal Disclaimer(s)
The terminal disclaimer filed on 8/27/25 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12,128,090, has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Rejections - 35 USC § 103-Maintained
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 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.
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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 57-59, 61-63, and 65-76 remain rejected under 35 U.S.C. 103 as being unpatentable over Suiter et al. (“Recombinant Human Von Willebrand Factor (rhVWF): First-In-Human Study Evaluating Pharmacokinetics, Demonstrating Safety and Tolerability In Type 3 Von Willebrand Disease”. Blood, Volume 116, Issue 21, 2010, Page 237, ISSN 0006-4971,https://doi.org/10.1182/blood.V116.21.237.237.
(https://www.sciencedirect.com/science/article/pii/S0006497119423070) (also cited in 11/9/22 IDS)
in view of Moses et al. (U.S. Patent Publication No. 20180051067).
Suiter (abstract) teach prophylactically treating any type of bleeding disorder (which includes spontaneous) – by enhancing stabilization of endogenous FVIII (3rd to last sentence, abstract) - in someone with VWD (which intrinsically includes mild to severe) – by administering 50 IU/kg of rhVWF (first concentration recited/tested, abstract), where the rhVWF is admnistered alone (last sentence, abstract), once a therapeutic baseline level of FVIII is achieved (last sentence, abstract):
Abstract
Abstract 237
Von Willebrand Disease (VWD) is an inherited rare bleeding disorder caused by a deficiency of von Willebrand factor (VWF). VWF is the largest soluble multimeric plasma glycoprotein, which facilitates platelet aggregation and stabilizes FVIII in the circulation. Patients with type 3 disease display severe hemorrhagic symptoms, mainly in mucosal tissues, muscle and joints. Replacement of VWF stabilizes endogenous FVIII to hemostatic levels within hours. Commercially available VWF/FVIII concentrates are plasma-derived (pd) and subject to limitations such as donor dependency, risk of blood-borne pathogen transmission, lack of high molecular weight VWF multimers, and variation in multimer composition. A novel recombinant human VWF (rhVWF) has been developed using a plasma-free method, which represents the largest protein ever produced using recombinant technology. Safety, tolerability and pharmacokinetics of the rhVWF combined at a fixed ratio with rFVIII were investigated in a Phase 1 multicenter, international clinical study in 31 patients with type 3 VWD and severe type 1 VWD. Four concentrations of rhVWF (2, 7.5, 20 and 50 IU VWF:RCo/kg) were administered in a dose-escalating manner in separate cohorts. rhVWF was well tolerated, and no thrombotic events, VWF inhibitors or other serious adverse reactions were observed. Pharmacokinetics of rhVWF/rhFVIII (50 IU VWF:RCo/kg and 38.5 IU FVIII/kg) compared with pdVWF/pdFVIII (50 IU VWF:RCo/kg and 21 IU/kg FVIII/kg) were evaluated in a sub-group of 8/31 patients using a randomized, crossover design (8-day minimum washout period). Interim data in 8 subjects show a higher degree of secondary FVIII activity with rhVWF/rhFVIII compared to pdVWF/pdFVIII (see Figure 1) that is not solely due the difference in the rhVVF:FVIII infusion ratio (1.3:1 rhVWF/rhFVIII vs. approximately 2:1 pdVWF/pdFVIII). The pharmacokinetics of the rhVWF:RCo and pdVWF:RCo were comparable and were also reflected in the VWF:Ag and collagen binding activity. Evidence is also provided for the in vivo cleavage of the ultra-high molecular weight multimers of rhVWF by endogenous ADAMTS13. In summary, interim data from the ongoing Phase 1 study, demonstrate that rhVWF is safe and well tolerated, has VWF:RCo pharmacokinetics that are comparable to pdVWF and enhances stabilization of endogenous FVIII. Multiple doses of rhVWF/rhFVIII would be expected to have beneficial effects in major surgery and severe mucosal bleeding events. These data would also support the treatment concept to administer rhVWF alone once a therapeutic baseline level of endogenous FVIII is achieved (after 1–2 doses).
Suiter therefore teach the state of the prior art as early as 2010 was that PHOSITA recognized that rhVWF could be administered alone to sustain/stabilize endogenous FVIII levels in order to prophylactically treat (reduce, prevent) spontaneous episodes in subject with VWD (mild to severe)).
However, Suiter does not expressly teach “twice-weekly” administration thereof.
Moses fills this gap by teaching such (para 171):
(171) A further aspect is the use of a modified VWF molecule as defined hereinabove for reducing the frequency of administration of VWF in a treatment of VWD. The frequency of intravenous or subcutaneous administration of VWF may be reduced to twice per week. Alternatively, the frequency of intravenous or subcutaneous administration of VWF may be reduced to once per week. That is, the modified VWF molecule of the invention is administered once or twice per week.
Thus, the claimed are deemed expressly taught or suggested by Suiter in view of Moses, or based on routine optimization of standard pharmaceutical parameters therein (concentration, amounts, etc.).
As for applying such equally to “severe” von Willebrand Disease (VWD) type 3 would have prima facie obvious for the reasons of record just as applying such to any form of VWD would have, absent further evidence to the contrary.
The claims are equally rejected as being directed to known spontaneous bleeding episodes within the references of record or the state of the art here.
The claims are equally rendered obvious as to those directed to natural end results based on the treatment protocal taught/suggested within the prior art of record.
Thus, the claimed invention remains found prima facie obvious over Suiter et al./Moses.
Response to Amendments/Arguments
Applicant’s amendments (e.g. requiring now 1 full year of the once weekly regimen (about 40-80 IU/kg) of prophylactic rVWF to treat spontaneous bleeding episodes in a human with severe VWD) and arguments thereto have been fully considered but not found persuasive. As noted, Suitor teaches the ‘inventive concept’ (prophylactic treatment for of bleeding disorders for any reason (e.g. spontaneous) of anyone with any degree of VWF). Moses teaches the instantly claimed dosing of once weekly. As for duration, whether such is 1 month, 2 months, 6 months, 12 months, 24 months or beyond - such is merely a matter of routine optimization by PHOSITA depending on e.g. whether someone with VWF is still evidencing the need for such based on spontaneous bleeds without. Further there is a lack of control test data as to whether duration of time of such a regimen has any real impact on effect. Based on the instantly amended claim scope, there would need comparable evidence of someone who was treated for say 10 months versus 12 months versus 14 months, by example to show some kind of curve of improved results obtained after X period of time versus before and/or after, to show something unexpected. Control data of this duration versus other durations.
Therefore, the lack of test data is not found commensurate in scope to that claimed – as no secondary considerations of unexpected results have been shown to overcome the prima facie case of obviousness. Thus, the rejection is of record is maintained, absent further control evidence to support the instantly amended claim scope of the invention.
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 MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAURY A AUDET/Primary Examiner, Art Unit 1654
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