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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 13, 2026 has been entered.
Claim Status
Claims 1-3, 8-10, 22, 25, and 28 are under consideration in this office action.
Withdrawn Objections/Rejections
Any objection or rejection of record pertaining to cancelled claims 11, 18, and 21 is rendered moot by applicant’s cancellation of said claims.
Modified Rejections
Claim Rejections - 35 USC § 103
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.
Claims 1-3, 8-10, 22, 25, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over US 20190062438 A1, published February 28, 2019 (“Owczarek”; PTO-892 from 12/15/2025) in view of US 20170252436, published September 7, 2017 (“Diluzio”; PTO-892 from 12/15/2025) and De Luca et al, published August 2020 (PTO-892 from 12/15/2025).
The claims are directed to a method of treating or preventing ARDS in a subject by administering an anti-CD131 antibody comprised of HCDR1-3 of SEQ ID NOs: 8-10 and LCDR1-3 of SEQ ID NOs: 11-13.
Owczarek teaches that each of IL-3, IL-5, and GM-CSF signal through a multimeric receptor made up of a common b chain (this is CD131), and a cytokine specific a chain [0005]. Owczarek teaches an anti-CD131 antibody that neutralizes signaling by IL-3, IL-5 and GM-CSF (abstract; [0008]), as in the compound that binds to CD131 and neutralizes signaling by IL-3, IL-5, and GM-CSF of instant claim 1. The CD131 binding protein inhibits GM-CSF-induced proliferation of TF-1 cells [0013], demonstrating that this antibody inhibits GM-CSF activity. In embodiment (cxvii), the VH comprises CDRs 1, 2, and 3 of SEQ ID NO: 64 and a VL comprising CDRs 1, 2, and 3 of SEQ ID NO: 5 [0226]. SEQ ID NO: 64 of Owczarek is comprised of instant heavy chain CDRs of SEQ ID NOs: 8-10 and SEQ ID NO: 5 of Owczarek is comprised of light chain CDRs of SEQ ID NOs: 11-13, as in the anti-CD131 antibody of instant claim 1. This anti-CD131 antibody of Owczarek is comprised of a VH/VL pair of SEQ ID NO: 64/SEQ ID NO: 5, which are comprised of VH/VL pair of instant SEQ ID NO: 6/18 and the CDRs therein of claim 22. Claim 22, subpart c is directed to a heavy chain comprising SEQ ID NO: 8 and a light chain comprising SEQ ID NO: 9. It is noted that SEQ ID NO: 8 and SEQ ID NO: 9 correspond to CDR1 and CDR2, respectively, of VH of SEQ ID NO: 64 of Owczarek.
The anti-CD131 antibody of Owczarek may be used in a method of treating or preventing a condition caused by exacerbated CD131 signaling [1143], including inflammation [1138], interstitial lung disease [1145], a respiratory condition [1149], and chronic eosinophilic pneumonia, as in the infection of instant claim 2 and the interstitial pneumonia or instant claim 8.
Owczarek does not explicitly teach a method for preventing or treating acute respiratory distress syndrome (ARDS).
Diluzio teaches inhibitors of the GM-CSF receptor, including antibodies directed to GM-CSF alpha chain and CD131, which is the common beta chain of GM-CSF, IL-3, and IL-5 [0120]. The inhibitors of GM-CSF receptor can be used to treat or prevent disease in patients in need; the patients in need of treatment may be suffering from acute respiratory distress syndrome [0219], as in instant claims 1 and 28.
De Luca et al teaches a method for effectively treating SARS-CoV-2 infection in a patient with the anti-GM-CSF receptor-alpha monoclonal antibody mavrilimumab (abstract), as in SARS-CoV limitation of instant claim 3. Citing an earlier study, De Luca teaches that of 201 patients admitted to hospital with COVID-19, 42% developed acute respiratory distress syndrome and 52% of these patients died, demonstrating that ARDS is a complication of SARS-CoV-2 infection and the need for effective treatment to prevent escalation to a critical stage (pg 3466, “Research in context”).
De Luca teaches that the mavrilimumab therapy is administered in combination with standard management (abstract), including mechanical ventilation (figure 2) and antibiotic treatment (e471, column 2), as in claim 25.
Given that Owczarek teaches the anti-CD131 antibody (i.e. anti-GM-CSFR-b antibody) of claim 1 in a method of treating respiratory condition and further given that Diluzio teaches a method of treating and preventing ARDS by administering an antibody that binds to CD131 or GM-CSFR-a and DeLuca teaches the utility of an anti-GM-CSFR-a antibody in the treatment of ARDS related to SARS-CoV-2 infection, one of ordinary skill in the art would have been able to reasonably predict the efficacy of the antibody of Owczarek in the treatment of ARDS associated with infection or ARDS in a subject with interstitial pneumonia, especially since the Owczarek antibody identifies this antibody as a treatment for inflammatorydisease associated with exacerbated CD131 and GM-CSF signaling.
Because Owczarek in view of Diluzio teach a method of treating ARDS by administering an anti-GM-CSF-R antibody that targets beta subunit CD131 and GM-CSFR-a, and De Luca teaches a method of treating ARDS related to SARS-CoV-2 infection by administering an anti-GM-CSFR-a antibody, one of ordinary skill in the art would have a reasonable expectation of successfully using the antibody of Owczarek in the treatment of ARDS associated with SARS-CoV-2, especially in view of the demonstrated efficacy of the antibody of De Luca (which only targets GM-CSF-R signaling) in the treatment of ARDS. Because De Luca teaches that inhibiting GM-CSF signaling by blocking its receptor is useful to treating SARS-CoV-2 related ARDS, one of ordinary skill in the art would appreciate that another blocker of GM-CSF signaling that targets the other domain of the receptor (i.e. the anti-CD131 antibody of Owczarek) would also be efficacious in the treating the disease.
See MPEP 2141.III: “Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art.” Here, one looking to use an antibody to inhibit GM-CSF receptor signaling for the treatment of ARDS would use the antibody of Owczarek and have a reasonable expectation of success. This is because the ordinary artisan has good reason to pursue known options within their technical grasp to obtain predictable results (MPEP2143.B). Such would amount to the simple substitution of one element for another with overlapping functionality (i.e. the antibody of Owczarek for that of De Luca or Diluzio) to obtain predictable results. The motivation to do so comes from Owczarek ([1137]-[1138], [1143]) and Diluzio [0021], which teaches the potential clinical benefit of compounds targeting CD131 for the treatment of inflammation and infection in respiratory conditions.
Response to Arguments
Applicant's arguments filed August 13, 2006 regarding the rejections under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant asserts that Diluzio disclosure is related to the field of antibody and pharmaceutical formulations and does not relate to methods of treatment (remarks, pg 8). Applicant is directed to [0017] of Diluzio, which discusses “methods… applying these formulations in the treatment of subjects suffering from disease which would benefit from the administration of compounds neutralizing GM-CSF.” Also, see Diluzio [0125], which states, “preferred methods of administration are such that after administration the compound neutralizing GM-CSF is present in the blood in effective doses.”
Applicant argues that anti-CD131 antibodies are not a species of the anti-GM-CSFR antibodies of Diluzio; as Diluzio antibodies are concerned with inhibition of GM-CSF signaling only and not IL-5 or Il-3 signaling (pg 9). Although the examiner concedes that the focus of Diluzio is on GM-CSF activity, Diluzio broadly teaches methods of treating ARDS using antibodies that target both CD131 and GM-CSFR-a. As this focus is narrower scope than the claimed antibody (which also inhibits IL-5 and IL-3 signaling), the examiner maintains their position that the method to treat ARDS with anti-CD131 antibody is taught by Diluzio. Further, the new rejection is made over Owczarek in view of Diluzio and DeLuca, where Owczarek teaches the antibody and methods of treating lung disease by inhibiting IL-3, IL-5 and GM-CSF, Diluzio teaches inhibitors of GM-CSF-R for the treatment of ARDS, and DeLuca teaches antibody to GM-CSFR-a for the treatment of ARDS. Given that the claimed antibody has a broader functional scope than the inhibitors of Diluzio and DeLuca (i.e. it inhibits GM-CSF, IL-3, and IL-5), it would have been obvious to the ordinary artisan that applying the broader inhibitor would have the same effect and the results would have been reasonably predictable. Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. “Good science and useful contributions do not necessarily result in patentability.” PharmaStem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342 (Fed. Cir. 2007).
Regarding the examiner’s statement that the antibody inhibitors of Diluzio, DeLuca, and Owczarek are functional equivalents and applicant’s response that antibodies directed to GM-CSFRa and CD131 operate through materially different mechanisms and produce materially different biological consequences, the examiner has modified the rejection to make clear that the anti-CD131 antibody overlaps functionally with the other GM-CSFR inhibitors of Diluzio and DeLuca and has removed language regarding functional equivalents. The examiner, however, does maintain their position that an inhibitor of either alpha subunit or beta subunit of GM-CSFR would be expected to be associated with similar outcomes in the treatment of ARDS. DeLuca is used to teach that antibodies that target the same pathway as anti-CD131 antibody can be used to treat successfully ARDS. DeLuca teaches that patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS), a hyperinflammatory response, and teaches treatment with anti-GM-CSFRa antibody to inhibit pro-inflammatory pathways (pg e466, column 1). In conditions with hyperinflammation, immunomodulation is likely to be beneficial, where an antibody to GM-CSFRa disrupts downstream signaling of the GM-CSF receptor. As Owczarek provides a known antibody that inhibits the same signaling pathway (the claimed antibody inhibits the GM-CSF receptor) and is already indicated for respiratory/lung disease, one of ordinary skill in the art would have been motivated to use the antibody of Owczarek to treat ARDS as taught by DeLuca with a reasonable expectation that inhibition of GM-CSFR would provide the disclosed therapeutic effect.
Applicant asserts that the prior art teaches away from using an anti-CD131 antibody, citing Trapnell et al, which teaches that pulmonary aveolar proteinosis (PAP) is a risk associated with administration of an antagonist of GM-CSF signaling (pg 11). A known treatment-associated risk, however, does not necessarily negate a motivation to combine references for a method of treating, especially when there is sufficient evidence that treatment that targets inflammatory cytokine pathways is effective to treat severe inflammation. As admitted by applicant, the cited references do not address PAP as a potential risk (pg 11), but given the potential anti-inflammatory benefit of the anti-CD131 antibody, a skilled artisan would pursue the treatment despite the known PAP risk, because the risk is low. Applicant is directed to Burmester et al (see instant PTO-892), which is an evidentiary reference for response to arguments and is not cited as a new reference in the rection. Burmester et al teaches results from a phase IIb clinical trial for mavrilimumab, an anti GM-CSF alpha antibody in the treatment of rheumatoid arthritis (abstract). Mavrilimumab treatment was not associated with any confirmed or suspected case of PAP in the over 300 patients evaluated (pg 1028, column 1, para 1; abstract).
Applicant argues that Diluzio contains only passing reference to the common beta chain and there is no specific embodiment in Diluzio that includes an anti-CD131 antibody in a method of treating ARDS (pg 9). Further, applicant asserts that the examiner is applying hindsight to pick and choose without any motivation or rationale; for example, ARDS must be selected from the extensive list of disease and antibodies recited in Diluzio (pg 12). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). When Diluzio is considered with DeLuca, the selection of ARDS among the list disclosed by Diluzio for the method of treating is made obvious. Further, Diluzio and DeLuca re used as a secondary references. These secondary references do not need to teach the antibody; rather, these references are used to teach that inhibitors of GM-CSFR, including anti-CD131 antibodies, were known anti-inflammatories and had been contemplated for the treatment of ARDS.
Notably, a new function can support a method of use claim only if it leads to a new and nonobvious use. However, because the prior art teaches a method of administering the product in the same way and the same disease, the claimed method is not novel. The teachings of Diluzio and De Luca provide the motivation that would have led one of ordinary skill to modify the Owczarek antibody and method to arrive at the claimed invention to treat ARDS. The rejections under 35 U.S.C. 103 are maintained.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
