RESPONSE TO APPLICANT’S AMENDMENT
1. Applicant's amendment, filed 04/06/2026, is acknowledged.
2. Claims 1, 2, 9, 12, 14-15 are pending and under examination as they read on a method of treating an acute chest syndrome in a patient suffering from sickle cell disease with an IL-6 inhibitor is antibodies directed against the IL-6 receptor (IL-6R) and the species of tocilizumab
3. The following new grounds of rejection are necessitated by the amendment submitted 04/06/2026.
4. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claims 1-2, 9 and 12 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Odievre et al (Am J Hematol . 2020 Aug;95(8):E192-E194, First published 01 May 2020, IDS).
Odievre et al commented on De Luna et al recently reported a favorable outcome of an acute chest syndrome (ACS) related to a SARS‐Cov‐2 infection treated with tocilizumab (TCZ) (i.e., anti-IL-6R antibody), in a 45‐year‐old male patient with homozygous sickle cell disease (SCD). Following this successful observation, TCZ was administered to a teenage girl (i.e., patient) with SCD who developed a severe COVID‐19 associating ACS and pulmonary embolism, the patient required non‐invasive ventilation (i.e., respiratory support) (see page E192, right col., 1st ¶). Claim 7 is included because TCZ binds IL-6R residue 20-365 of SEQ ID NO: 2 as is evidenced by claims 8-9 which depend directly and indirectly from claim 7.
Applicant’s arguments, filed 04/06/2026, have been fully considered, but have not been found convincing.
Applicant submits that Odievre et al teaches measurement of IL-6 is increased in the plasma of COVID-19- infected patients and in serum after a single tocilizumab injection but does not measure IL-6 in sputum.
This is not found persuasive because claims 1-2, 9 and 12 do not required the measurement of IL-6. Applicant argues limitations that are not claimed.
Applicant argues that the claimed invention is a method of administering tocilizumab or other anti-IL-6R antibodies to a subject suffering from SCD for the treatment of ACS independent of detectable respiratory viruses or atypical bacteria. See paragraph [0036] of the published application, which discloses that "screening for respiratory viruses and atypical bacteria (C pneumoniac and M pncumonia) was negative for all patients, as were blood cultures and bacteriological examination of sputum."
This is not found persuasive because the claims are directed to a genus of subjects suffering from SCD for the treatment of ACS including those with detectable respiratory viruses or atypical bacteria. A species anticipates a genus. The prior art meets the single step of treating an ACS in a patient suffering from sickle cell disease comprising administering tocilizumab.
6. Claims 1-2, 9 and 12 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Luna et al (Am J Hematol. July 2020, page 876-878. https://doi. org/10.1002/ajh.25833, IDS).
De Luna et al teaches that rapid and severe Covid-19 pneumonia with severe acute chest syndrome in a sickle cell patient successfully treated with tocilizumab (see title). De Luna teaches that for our patient who has an acute chest syndrome (ACS) related to a SARS‐Cov‐2 infection, given the prior history of severe SCD and the potential risks, treatment with hydroxychloroquine and TCZ were initiated, with a positive resolution. The patient was Supplemental oxygen through Venturi mask (i.e., artificial respiratory support, mechanical ventilation). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibodythat inhibits signal transduction by binding sIL-6R and mIL-6R (see last ¶).
Applicant’s arguments, filed 04/06/2026, have been fully considered, but have not been found convincing.
Applicant submits that the skilled person would interpret the De Luna et al document's teaching as focused on the management of COVID-19 pneumonia. There is no explicit disclosure or motivation to extend the therapeutic strategy of IL-6 inhibition to the treatment of ACS outside
the context of viral pneumonia. Accordingly, the claimed invention presents a novel
therapeutic application that is not derivable from De Luna alone.
Applicant submits that the claimed invention is a method of administering tocilizumab or
other anti-IL-6R antibodies to a subject suffering from SCD for the treatment of ACS
independent of detectable respiratory viruses or atypical bacteria. See paragraph
[0036] of the published application, which discloses that "screening for respiratory
viruses and atypical bacteria (C pneumoniae and M pneumonia) was negative for all
patients, as were blood cultures and bacteriological examination of sputum."
This is not found persuasive because the claims are directed to a genus of subjects suffering from SCD for the treatment of ACS including those with detectable respiratory viruses or atypical bacteria. A species anticipates a genus. The prior art meets the single step of treating an ACS in a patient suffering from sickle cell disease comprising administering tocilizumab.
7. Claims 1 and 9 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Watson et al (Pediatric Blood and Cancer, (June 2019) Vol. 66, Supp. Supplement 2, pp. S253. Abstract Number: 731).
Watson et al teaches that a 14 year old female with sickle cell disease received a pRBC transfusion for vaso‐occlusive disease and acute chest syndrome. Eight days after transfusion she suffered acute onset of severe extremity pain that was followed by new onset of fever, hypertension and respiratory decompensation. She subsequently survived an 8 day ICU stay requiring multiple pRBC transfusions due to hypoxemia and received multiple immunomodulators including tocilizumab.
Applicant’s arguments, filed 04/06/2026, have been fully considered, but have not been found convincing.
Applicant argues that the immunomodulators were administered to treat the hemolytic transfusion reaction, rather than ACS, and Watson fails to teach each and every element of the claimed invention.
This is not found persuasive because the prior art meets the single step of treating an ACS in a patient suffering from sickle cell disease comprising administering tocilizumab.
8. Claims 1 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sivapalaratnam et al. (British Journal of Haematology, Sept. 2019, 186, e112–e214).
Sivapalaratnam et al teach a case of post-transfusion hyperhaemolysis syndrome (PTHS) treated with tociluzimab in a 33-year-old man with homozygous sickle cell disease (HbSS). The patient had a history of recurrent episodes of the acute chest syndrome (ACS) and also two previous episodes of PTHS following exchange transfusion for treatment of ACS (p. e212, left col, 3rd ¶). .
Applicant’s arguments, filed 04/06/2026, have been fully considered, but have not been found convincing.
Applicant submits that the present invention is a method of treating ACS, rather than
PTHS. Sivapalaratnam fails to teach administration of tocilizumab as a treatment for
ACS and therefore fails to teach each and every element of the claimed invention
This is not found persuasive because the prior art meets the single step of treating an ACS in a patient suffering from sickle cell disease comprising administering tocilizumab.
9. Claims 1 and 9 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Linpower et al. (British Journal of Haematology, (March 2019) Vol. 185, Supp. Supplement 1, pp. 120‐121. Abstract Number: BSH19‐PO‐136) for the same reasons set forth in the previous Office Action mailed 01/08/2026.
Applicant’s arguments, filed 04/06/2026, have been fully considered, but have not been found convincing.
The present application also discloses that the inventors disclose administration of tocilizumab as a treatment of ACS, rather than hemolysis. Therefore, Linpower fails to teach each and every element of the claimed invention .
This is not found persuasive because the prior art meets the single step of treating an ACS in a patient suffering from sickle cell disease comprising administering tocilizumab.
10. 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.
11. Claims 1-2, 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Watson et al (Pediatric Blood and Cancer, (June 2019) Vol. 66, Supp. Supplement 2, pp. S253. Abstract Number: 731), Sivapalaratnam et al. (British Journal of Haematology, Sept. 2019, 186, e112–e214) or Linpower et al. (British Journal of Haematology, (March 2019) Vol. 185, Supp. Supplement 1, pp. 120‐121. Abstract Number: BSH19‐PO‐136); each in view of US 20130123185 or Howard et al (British Journal of Haematology, 2015, 169, 492–505) for the same reasons set forth in the previous Office Action mailed 01/08/2026.
Applicant’s arguments, filed 04/06/2026, have been fully considered, but have not been found convincing.
Applicant submits that neither of these references compensate for the deficiencies of Watson, Sivapalaratnam and Linpower. Applicant concluded that there is no combination of any of Watson, Sivapalaratnam or Linpower with US 2013123185 or Howard that makes the claimed invention obvious.
However, it remains the Examiner’s position that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide a mechanical ventilation taught by the `185 publication and Howard et al in the method of treating acute chest syndrome taught by Watson et al, Sivapalaratnam et al and Linpower et al because mechanical ventilations are necessary to support patients with severe ACS and older patients.
12. Claims 1-2, 9, 13 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Odievre et al (Am J Hematol . 2020 Aug;95(8):E192-E194, First published 01 May 2020, IDS), De Luna et al (Am J Hematol. July 2020, page 876-878. https://doi. org/10.1002/ajh.25833, IDS), Watson et al (Pediatric Blood and Cancer, (June 2019) Vol. 66, Supp. Supplement 2, pp. S253. Abstract Number: 731), Sivapalaratnam et al. (British Journal of Haematology, Sept. 2019, 186, e112–e214) OR Linpower et al. (British Journal of Haematology, (March 2019) Vol. 185, Supp. Supplement 1, pp. 120‐121. Abstract Number: BSH19‐PO‐136); each in view of Al Biltagi et al (Pediatric Pulmonology. 2020;55:2055–2063. https://doi.org/10.1002/ppul.24871)
The teachings of the Odievre et al, De Luna et al, Watson et al, Sivapalaratnam and Linpower et al have been discussed, supra.
Odievre et al further teaches that after a single TCZ injection, serum IL-6 level first increases rapidly before decreasing. In the absence of significant clinical improvement with persistence of an elevated IL-6 level, a second and a third dose of TCZ can be administered after 12 and 24-36 hours respectively (see Page E193, left col., 2nd ¶).
The reference teachings differ from the claimed invention only in the recitation that the method further comprising prior to the administering step, detecting an increase in IL-6 concentration in a sputum sample obtained from the subject as compared to a plasma sample obtained from the subject in claim 14, wherein the increase in IL-6 concentration in the sputum sample is at least 150-fold higher than that in the plasma sample in claim 15.
Al Biltagi et al teach that sickle cell disease (SCD) is relatively common in Bahrain, and airway inflammation in patients with SCD is usually multifactorial. This study aimed to evaluate lung function and induced m levels of interleukin-6 (IL-6) in Bahraini children and adolescents with SCD and assess their relationship with the recurrence of acute chest syndrome (ACS). Al Biltagi et al teaches that residual volume and sputum IL-6 levels were significantly higher in the patient group than in the control group. PFT parameters were more compromised in the patient subgroup with a history of ACS and older than 12 years compared with the subgroup without a history of ACS and the subgroup under 12 years of age. PFTs revealed significant negative correlations with age, number of ACS events, and sputum IL-6 levels. Al Biltagi et al concluded that pulmonary function was observed to worsen with disease progression, and it worsened with older age and repeated occurrence of ACS. Induced sputum IL-6 levels reflected the degree of lung inflammation in affected patients and were associated with more impairment in various PFT parameters (abstract). Al Biltagi found higher induced sputum IL-6 levels in children with homozygous SCD than children in the control group (healthy subject). Their study measured sputum—not serum—levels of IL-6 with an aim to evaluate the pulmonary inflammatory status in SCD (page 13, 2nd ¶). No previous studies have measured sputum IL-6 levels in children with SCD (page 14, top ¶).
Given that higher sputum IL-6 level is a biomarker for patient with history of ACS, those skilled in the art would have had a reason to evaluate the level of sputum IL-6 ACS prior to the treatment taught by dievre et al, De Luna et al, Watson et al, Sivapalaratnam and Linpower et al to identify the patients qualify for the anti-IL-6 receptor antibody, tocilizumab treatment.
While Al Biltagi et al does not compare the sputum IL-6 level to plasma sample, however in any case, the end-result is the same, higher level of sputum IL-6 level whether it is compared to plasma sample or healthy subject. Comparing the sputum IL-6 to plasma sample is an obvious variation of the teaching of Al Biltagi et al.
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.
13. No claim is allowed.
14. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 date of this final action.
15. 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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April 23, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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