DETAILED ACTION
1. 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 05/05/2023, is acknowledged.
3. Claims 1-13 are pending.
4. Applicant’s election with traverse of Group II, claims 1-3, 7-9 and 12 directed to 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, filed on 12/11/2025, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
5. Claims 4-6, 10-11 and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 1-3, 7-9 and 12 are 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.
7. Applicant’s IDS, filed 05/05/2023, 12/11/2025, 12/11/2025, is acknowledged. However, the IDS filed 12/11/2025 is duplicate, thus one of them is crossed out.
8. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
9. Claims 1-3, 7 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims encompass a broad genus of IL-6 inhibitors as well as a genus of anti-IL-6R antibodies in the treating of acute chest syndrome (ACS) in a patient suffering from sickle cell disease.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of treating ACS. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
The specification discloses that "IL-6 inhibitor" refers to any compound that is able to inhibit the IL-6 signaling pathway. The IL-6 inhibitor to be used in the methods described herein is a molecule that blocks, suppresses, or reduces (including significantly) the biological activity of an IL-6 cytokine, including downstream pathways mediated by IL-6 signaling. Thus, the term
"IL-6 inhibitor" implies no specific mechanism of biological action whatsoever, and is deemed to expressly include and encompass all possible pharmacological, physiological, and
biochemical interactions with an IL-6 cytokine or its receptor whether direct or indirect (see page4, lines 35+).
Further, the specification discloses that the IL-6 inhibitor is selected from the group consisting of antibodies directed against the IL-6 cytokine and antibodies directed against the IL-6 receptor (e.g., an antibody specifically binds to IL-6R) (see page 5, lines 1+).
The specification fails treat any disease including acute chest syndrome with an IL-6 inhibitor including anti-IL-6R antibodies such as tocilizumab.
The specification at page 7, lines 29+, discloses that the anti-IL-6R antibody is tocilizumab, sarilumab, or levilimab (BCD-089).
The specification describes the IL-6 inhibitor is antibodies directed against the IL-6 cytokine and antibodies directed against the IL-6 receptor (e.g., an antibody specifically binds to IL-6R) [0014]. The IL-6 inhibitors refer to any compound that is able to inhibit the IL-6 signaling pathway [0013]. The anti-IL-6R inhibitors is an antibody that binds to the amino acid sequence that ranges from the amino acid residue at position 20 to the amino acid residue 365 in SEQ ID NO:2. Besides tocilizumab, sarilumab, or levilimab (BCD-089), the specification does not describe the complete structure of any compound able to inhibit the IL-6 signaling pathway.
Further, the specification does not describe the partial structures, or physical properties, or chemical properties of any compound that able to inhibit the IL-6 signaling pathway and treat ACS.
While the specification describes the amino acid sequence of IL-6R (SEQ ID NO:2), the specification does not describe any correlation between the sequence and the structure of any agent that is able to inhibit the IL-6 signaling pathway and treat ACS.
Besides tocilizumab, sarilumab, or levilimab (BCD-089), the level of skill and knowledge in the art is that there are no known compounds that able to inhibit the IL-6 signaling pathway and treat ACS and no known correlation between any structural component and the ability to inhibit IL-6 signaling pathway and treat ACS. Thus, the disclosure does not allow one of skill in the art to visualize or recognize the structure of any compound required to practice the claimed method. Accordingly, one of ordinary skill in the art would conclude that the applicant would not have been in possession of the claimed method of using an IL-6 inhibitor that able to inhibit the IL-6 signaling pathway and treat ACS because an inhibitor possessing the desired activity required to practice the method is not adequately described and was not known in the art.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of IL-6 inhibitors falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Claims 3 and 7 are directed to a broad genus of anti-IL-6R antibodies in the treatment of acute chest syndrome.
The USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018.
See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
In contrast to applicant’s reliance of describe the epitope 20-365 of SEQ ID NO: 2 in providing a fully characterized antigen / specific epitope as well as claiming structural elements of the antigen of treating ACS, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-IL-6R antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad.
However, the anti-IL-6R antibodies are required to practice the invention. The specification fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely relying on the identification of cytokine receptor IL-6R as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
The claims are directed to a genus of anti-IL-6R antibodies. However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-IL-6R antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e. the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the claimed broadly class of antibodies and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of antibodies directed against the IL-6 receptor (IL-6R), the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163
The specification at best describes plan for making antibodies that bind IL-6R and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
10. 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.
11. Claims 1-3, 7-9 and 12 are 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.
The reference teachings anticipate the claimed invention.
12. Claims 1-3, 7-9 and 12 are 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 ¶).
The reference teachings anticipate the claimed invention.
13. Claims 1, 3, 7-9 are 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.
The reference teachings anticipate the claimed invention.
14. Claims 1, 3, 7-9 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 ¶). .
The reference teachings anticipate the claimed invention.
15. Claims 1, 3, 7-9 are 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).
Linpower et al teach a 33‐year‐old man with HbSS and a background of recurrent acute
chest syndrome (ACS) as well as previous episodes of hyperhaemolysis, who presented with another episode of ACS necessitating an emergency automated red cell exchange transfusion (ARCET) with 12 units of red cells. Macrophage activation is associated with hyperferritinemia, a surrogate for interlikin ‐6 (IL‐6). As the patient was not responding to IVIG/steroids therapy we tried tociluzimab, a humanised monoclonal antibody against the IL‐6‐ receptor (IL‐6R), impairing macrophage function. As his Hb continued to drop (nadir 32 g/L on day 12 post‐ARCET), he was treated with 8 mg/kg tocilizumab once daily for two days. As a clinical observation, his urine, previously deeply discolored, appeared clear the morning after
the first dose of Tocilizumab. On day two, after treatment with tocilizumab, his reticulocytes had increased from 128.5 10*9/L to 414 10*9/L, ferritin decreased from 18342 ug/L to 9923 ug/L, LDH decreased from 1667 u/L to 1427 u/L while there was no further drop in his Hb. Haemolysis markers kept steadily improving and his haemoglobin started increasing. The patient's Hb reached steady state on day 17 following treatment with tocilizumab. Treatment with Tocilizumab was well tolerated and not related to any adverse events.
The reference teachings anticipate the claimed invention.
16. 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.
17. Claims 1-3, 7-9 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).
The teachings of Watson et al, Sivapalaratnam et al and Linpower et al have been discussed, supra.
The reference teachings differ from the claimed invention only in the recitation that the patient needs artificial respiratory support in claim 2 which is mechanical ventilation in claim 12.
The `185 publication teaches that mechanical ventilation is necessary to support patients with severe ACS. In addition to respiratory support for patients, a standardized treatment protocol for acute chest syndrome will also include antibiotic therapy, bronchodilator therapy, fluid and pain management, and blood transfustions (Vichinsky E P, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. 2000; 342(25):1855-1865). Other possible treatment options for ACS, often by reducing incidence through treating sickle cell disease itself, have been contemplated [0006].
Howard et al invasive and non-invasive mechanical ventilation. Has been reported as necessary in up to 20% of cases and it is more likely to be required in older patients. In the large multicntre National Acture Chest Syndrom Study, mechanical ventilation was provided for 13% of patients, of whom 81% recovered. (see page 496, left col, under Invasive and non-inasive mechanical ventilation).
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.
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.
18. No claim is allowed.
19. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 20250188175 A1
The `175 publication teaches and claims methods of treating a subject suffering from sickle cell crisis comprising administering an effective dose of 200 mg or less of tocilizumab to the subject, wherein the subject suffers from vaso-occlusive crisis, aplastic crisis, splenic sequestration crisis, hemolytic crisis, hyperhemolytic crisis, hepatic crisis, dactylitis, priapism, and/or acute chest syndrome.
20. 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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January 3, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644