RESPONSE TO APPLICANT’S AMENDMENT
1. Applicant's amendment, filed 09/28/2026, is acknowledged.
2. Claims 1, 4, 6, 12 are pending.
3. In view of the amendment filed on 09/28/2026, only the following rejections is remained.
4. 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.
5. Claims 1, 4, 6, 12 stand rejected under 35 U.S.C. 103 as being unpatentable over Novartis (Protocol No. CSEG101A2202, Jun 2018) in view of Johnson et al (Urology news, MARCH/APRIL 2018, VOL 22 NO 3) or Kousouranas et al (Ther Adv Urol 2017, Vol. 9(9-10) 227 –23) for the same reasons set forth in the previous Office Action mailed 03/27/2026.
Applicant’s arguments, filed 09/28/2026, have been fully considered, but have not been found convincing.
Applicant asserts that in order to establish inherency, the Examiner must show that the missing claim limitations are necessarily present in the prior art method and not merely probably or possibly present. In re Robertson, 169 F.3dd 743, 745 (Fed. Cir. 1999); Continental Can Co. USA V. Monsanto Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991). Probabilities or possibilities are insufficient. None of the cited references discloses the treatment of recurrent priapism in patients with crizanlizumab, let alone in a patient that has experienced ≥ 4 priapic events over 26 weeks or over 20 weeks or over 14 weeks or over 10 weeks prior to treatment, the reduction in frequency of priapic episodes, the reduction in frequency of priapic episodes by at least 25%, or any data demonstrating efficacy against priapism. Rather, the references merely disclose administration of crizanlizumab for SCD and identify priapism as one among numerous vaso-occlusive complications that may be monitored during clinical studies.
Applicant submits that the fact that priapism was included as a potential endpoint does not demonstrate that the claimed therapeutic result necessarily occurred. The Examiner points to no disclosure showing that any patient experienced the claimed reduction, much less that such reduction inevitably resulted from treatment. Furthermore, a disclosure of a treatment protocol does not anticipate a subsequently discovered therapeutic effect unless the effect necessarily and inevitably results from practicing the prior art method. The Examiner provides no evidence demonstrating such inevitability. At most, the cited protocol establishes that priapism was observed and monitored. It does not establish that reduction of priapic episodes was achieved or expected. Accordingly, the Examiner has not met the burden required to establish inherency.
However, it remains the Examiner’s position that given the Novartis teachings that treatment of SCD patients with crizanlizumab at 5.0 mg/kg demonstrated statistically significant, clinically meaningful, and robust efficacy results vs. placebo in reduction of annual rate of sickle cell-related pain crisis (SCPC) (also known as VOC leading to a healthcare visit) and delay of onset of VOC leading to a healthcare visit in a well-controlled Phase II clinical trial (SUSTAIN study) in a clearly defined SCD patient population (see section 2.6). Those of skill in the art would have been motivated to target the stuttering /recurring priapism patients taught by Johnson et al and Kousouranas et al references with the treatment taught by Novartis protocol.
The prior art cited by Examiner provides a reasonable expectation of success that the administration of the referenced dose regimen of crizanlizumab results in the 25% reduction of the frequence of stuttering/recurring priapic episodes in patients has experienced ≥ 4 priapic events over 10/14/20/26 weeks prior to treatment. see O’Farrell, 853 F.3d 894, 903-04 (Fed. Cir. 1988) (“Obviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success.”). Our reviewing court has held that when the prior art does not expressly disclose a claim limitation, inherency may supply the missing element. See Persion Pharm. LLC v. Alvogen Malta Operations Ltd., Case No. 18-2361 (Fed. Cir. Dec. 27, 2019) and Hospira,Inc. v. Fresenius Kabi USA, LLC., Case No. 19-1329, 19-1367 (Fed. Cir. Jan. 9, 2020). “Inherency is established in the context of obviousness when ‘the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art.’” Hospira, slip op. at 10 (Fed. Cir. Jan. 9, 2020) (citing Par Pharm. v. TWIPharm., Inc., 773 F.3d 1186, 1195—96 (Fed. Cir. 2014)). Here, the functions recited in the wherein clause flow naturally from the teachings of the prior art. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)).
The functions recited in the wherein clause flow naturally from the teachings of the prior art. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)). Here, the recited functional outcome would naturally and necessarily flow from inhibition of P-selectin by administering crizanlizumab. Accordingly, the prior art teaches the same method, the product used in the reference method are the same as the claimed method. Therefore, the claimed functional outcome would naturally and necessarily flow from inhibition of P-selectin with the crizanlizumab in treating stuttering /recurring priapic episodes.
The recitation “the frequency of priapic episodes is reduced by 25%, wherein the patient has experienced ≥ 4 priapic events over 26/20/14/10 weeks prior to treatment” would naturally and necessarily flow from inhibition of P-selectin with the crizanlizumab in vivo.
Applicant submits that the Novartis protocol relates to a Phase II trial intended to evaluate the safety and efficacy of SEG101/crizanlizumab in sickle cell disease (SCD) patients and merely discloses that priapism can be measured. Ataga I and Ataga II merely disclose the results of a clinical trial (SUSTAIN) that tested the ability of crizanlizumab to prevent pain crises in SCD, which can include priapism; however, as acknowledged by the Examiner, Ataga I further discloses that priapism was rare and there was no significant differences between either of the active-treatment groups and the placebo group (Ataga I, page 436, first column, last paragraph). These disclosures directly contradict the Examiner's position that reduction of priapic episodes by at least 25% necessarily results from administration of crizanlizumab. If the prior art study did not demonstrate a statistically significant effect on priapism, then the cited study cannot simultaneously establish that the claimed degree of efficacy inevitably occurs whenever crizanlizumab is administered. The Examiner attempts to dismiss Applicant's evidence as allegedly relating only to unexpected results. However, Applicant's position is not merely that the results were unexpected. Rather, Applicant relies upon the prior art itself to demonstrate that the claimed therapeutic outcome was neither disclosed nor shown to necessarily occur. Accordingly, the Novartis protocol and Ataga references fail to disclose the claimed reduction in priapic episodes and do not support an inherency finding.
However, it remains the Examiner’s position that given the Novartis teachings that treatment of SCD patients with crizanlizumab at 5.0 mg/kg demonstrated statistically significant, clinically meaningful, and robust efficacy results vs. placebo in reduction of annual rate of sickle cell-related pain crisis (SCPC) (also known as VOC leading to a healthcare visit) and delay of onset of VOC leading to a healthcare visit in a well-controlled Phase II clinical trial (SUSTAIN study) in a clearly defined SCD patient population (see section 2.6). Those of skill in the art would be motivated to target the stuttering /recurring priapism patients taught by Johnson et al and Kousouranas et al references with the treatment taught by Novartis protocol.
Applicant submits that none of the Novartis protocol, Ataga I and Ataga II discloses selecting patients on the basis of recurrent priapism history, but instead enrolled SCD patient based on vaso-occlusive crisis history generally. The Examiner treats all SCD patients as interchangeable with the specifically claimed recurrent-priapism patient population. Nothing in the cited references supports such equivalence. A patient population defined by repeated priapic episodes represents a distinct clinical subgroup having a different disease manifestation than the broader SCD population studied in the references. Accordingly the prior art methods are not "materially indistinguishable" from the claimed method.
However, the primary references teach that the treatment of SCD patients with crizanlizumab at 5.0 mg/kg demonstrated statistically significant, clinically meaningful, and robust efficacy results vs. placebo in reduction of annual rate of sickle cell-related pain crisis (SCPC) including priapism.
Applicant submits that Johnson and Kousouranas describe the existence and clinical characteristics of recurrent priapism, yet they do not suggest that inhibition of P- selection would reduce the frequence of priapic episodes, much less achieve the claimed level of efficacy. The cited references do not provide any teachings that improvements in vaso-occlusive crisis endpoints predict reductions in recurrent priapism frequency. Indeed, as discussed above, the Ataga I study itself did not demonstrate a significant effect on priapism. Accordingly, even assuming a motivation to investigate crizanlizumab in recurrent-priapism patients, the cited art fails to provide the requisite reasonable expectation that administration of the antibody would reduce priapic episodes by at least 25%.
The Novartis protocol, Ataga I, Ataga II, Hudnall, Johnson, and Kousouranas do not teach or suggest a method of reducing the frequency of priapic episodes in a patient suffering from SCD with crizanlizumab, let alone in a patient that has experienced > 4 priapic events over 26 weeks or over 20 weeks or over 14 weeks or over 10 weeks prior to treatment or that the number of priapic episodes could be reduced by 25%. Accordingly, a person of ordinary skill in the art would understand that the Novartis protocol, Ataga I, Ataga II, Hudnall, Johnson, and Kousouranas do not anticipate the claimed methods nor provide any reasonable expectation of success in achieving the reduction of the number of priapic episodes by the claimed methods.
However, it remains the Examiner’s position that given that P-selectin inhibitor SelG1 significantly reduced SCPC and appeared to be safe and well tolerated. Significant improvements were also achieved for several secondary endpoints including increases in times to first and second SCPC including priapism. Chronic inhibition of P-selectin with once-a-month IV dosing of SelG1 represents a novel and potentially new disease-modifying, prophylactic treatment option for patients with SCD. Those of skill in the art would motivate to target the SCD patients with SCPC related stuttering /recurring priapism taught by Johnson et al and Kousouranas et al references with the treatment taught by Ataga et al references.
6. No claim is allowed.
7. 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 extension fee 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.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM 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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October 8, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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