DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received June 22, 2026 are acknowledged.
Claims 4, 12, 13, 15, 19-33, and 36-39 have been canceled.
Claims 1-3, 5, 9-11, 16, and 18 have been amended.
Claims 40-41 have been added.
Claims 1-3, 5-11, 14, 16-18, 34, 35, 40 and 41 are pending in the instant application.
Claims 1-3, 5-11, 14, 16-18, 34, 35, 40 and 41 are under examination in this office action.
Information Disclosure Statement
The IDS form received 6/22/2026 is acknowledged and the references cited therein have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The rejection of claim 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been rendered moot by applicant’s claim amendments received November 20, 2025.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 rejection of claims 1-3, 5-11, 14, 16-18, and 34-36 under 35 U.S.C. 103 as being unpatentable over Shafner et al (WO 2019/084438, of record) in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments received June 22, 2026.
Specifically, the independent claims (i.e. 1 and newly presented 41) require the treated patient to have postpartum pregnancy associated atypical hemolytic uremic syndrome (p-aHUS) and to begin administration of an antibody having the recited SEQ ID numbers (which are those present in ravulizumab/ULTOMIRIS/ALXN1210/BNJ441) 1 to 15 days after delivery. The patient treated for postpartum p-aHUS was administered an anti-C5 antibody more than 15 days post-delivery and thus the cited references do not teach all of the limitations as presently recited in the claims.
Claims 1-3, 5-11, 14, 16-18, 34-35, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Shafner et al (WO 2019/084438, of record) in view of Huerta et al.
Shafner et al. disclose that antibodies that bind and neutralize C5 are to be administered to human patients to treat atypical hemolytic Uremic Syndrome (aHUS) as well as other thrombotic microangiopathies (see entire document, particularly the title, abstract, page 3, and claims). They disclose that the anti-C5 antibody named ravulizumab/ULTOMIRIS/ALXN1210/BNJ441 is particularly suitable for administration as part of their disclosed methods as it provides the advantage of binding C5 and preventing the cleavage of C5 into C5a and C5b thus preventing release of the proinflammatory mediator C5a and the formation of the pore-forming membrane attack complex (see for example lines 17-32 of page 3, lines 19-30 of page 20, and the claims). It should be noted that the biological sequences recited in the instant claims are the same sequences present in ravulizumab (see particularly the admission by applicant from line 19 of page 20 to line 7 of page 21 of the instant specification). The administered anti-C5 antibodies are disclosed as having the same binding affinities as those recited in the instant claims (compare lines 11-16 of page 4 as well as claims 10 and 11 to the text of instant claims 6 and 7). Such administered antibodies are further disclosed as comprising Fc mutations including M428L and N434S per EU numbering (see for example pages 3 and 4) and as being administered intravenously (see for example page 33 as well as claim 21). The dosing information, including both mass of drug as well as the timing of administration are the same when comparing the teachings of Shafner to that which is presently claimed (compare claims 1 and 2 to instant claims 9 and 10, and claims 12-14 to instant claim 11). Continued administration out to two years is also taught (compare claim 20 to instant claim 17). Conditions other than aHUS disclosed as amenable to treatment via the methods of Shafner et al. include HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count, a complication of pregnancy), spontaneous fetal loss and recurrent fetal loss (see particularly page 44). These teachings differ from the instant claimed invention in that Shafner et al. disclose treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of treating aHUS disclosed by Shafner et al on p-aHUS patients. This is because Shafner et al. teach their methods are generically useful in treating all forms of aHUS while Huerta et al. specifically teach that anti-C5 antibodies had complete efficacy in treating p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patients of Huerta et al. As such the prior art provides guidance, direction, and an expectation of success in selecting p-aHUS as a specific patient subpopulation to be treated within the larger genus of all aHUS as is taught by Shafner et al.
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant argues on many grounds. Applicant begins by pointing out the individual deficiencies in the cited prior art. With regard to Shafner et al., applicant argues that pregnant females were excluded from their studies and that such teachings in fact teach away from what is presently claimed. Applicant argues that while it is not disclosed by Shafner et al. if any of their treated patients were postpartum given the minimum 7 day screening period before beginning treatment in example 3 of Shafner et al. and the fact that p-aHUS symptoms do not necessarily begin immediately after delivery of the baby, there is no direction to beginning antibody administration 1-15 days after delivery (claim 1) or the more limited 5-11 days after delivery (new claim 40). Applicant argues that post filing clinical trial data related to example 1 of the instant application demonstrated that p-aHUS patients treated promptly after delivery (i.e.5-19 days after) had their symptoms resolve more quickly as compared to aHUS patients who began treatment anywhere from immediately after symptoms began to 215 months after symptoms arose, and therefore the clinical data is surprising and satisfies an unmet need (see particularly page 9 of applicant’s response). Regarding Huerta et al., applicant acknowledged that they disclose treating p-aHUS with eculizumab (i.e. the parental anti-C5 antibody that with 4 point mutations becomes ravulizumab) and additional therapies such as plasma exchange and heparin, but because some of the women developed kidney disease applicant believes that “The data in Table 2 teaches a skilled worker away from using a regimen consisting essentially of ravulizumab, because Huerta specifically notes that most of the CRs were attained when the patients were treated with PE, FPP, or heparin in addition to eculizumab therapy.” Thus applicant believes the rejection should be withdrawn.
These arguments have been considered and are not persuasive. On page 1 of the instant specification, it is explicitly disclosed that “aHUS triggered by pregnancy ("p-aHUS") is a rare and severe systemic disease associated with dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies.” Thus p-aHUS is a species that lies within the larger genus of aHUS. As such, applicant’s arguments about Shafner “teaching away” from the instant claimed invention is unusual. It should be pointed out that Shafner et al. is the WIPO publication of PCT/US2018/057760 which entered the US as application 16/757,512 while matured into US 12,128,101, and the applicant of both the issued patent and the instant application is Alexion Pharmaceuticals, Inc. Notably, the issued claims of the ‘101 patent recite aHUS and thus read upon all forms of the disease, including the species p-aHUS, and thus if applicant’s arguments were found to be persuasive, they would necessarily be an admission on the record by applicant that the full breadth of the issued inventions in the ‘101 patent were not enabled. However, applicant’s arguments are not persuasive, as failure to provide guidance and direction to a particular species within a larger disclosed genus simply means the disclosure fails to anticipate that which is claimed. Shafner et al. make no disavowal regarding the species of p-aHUS and silence cannot reasonably be considered as a teaching away. Further, it is well known in the medical arts that prompt treatment of a problem generally leads to quicker and better resolution of the problem. For example, following a cut, prompt cleaning and bandaging leads to early wound healing and less scaring as compared to having an untreated cut become infected and necrotic before beginning treatment. Thus, the fact that the promptly treated p-aHUS patients resolved their symptoms more quickly that generic aHUS patients who began treatment literally years after symptoms where first identified (e.g. 215 months is 17 years and 11 months) is hardly surprising. With regard to applicant’s assertions of an unmet need (which appears to be equivalent to “Long-Felt Need and Failure of Others as per MPEP 716.04) applicant has not shown persistent failure by others, and indeed the fact that p-aHUS was successfully treated by plasma exchange alone or in combination with eculizumab (as readily evidenced by Huerta et al., as well as De Sousa Amorim et al.(of record), Saad et al. (of record), and Delmas et al.) indicates that “long -felt need” criteria necessary to overcome a finding of obviousness for treating p-aHUS cannot be met, and note that an improving the prior art is not equivalent to solving an unmet/long-felt need.
With regard to Huerta et al., the fact that some women unfortunately developed kidney disease does not mean that p-aHUS was not successfully treated, and as set forth in the rejection of record, Huerta et al. explicitly state that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457). Applicant has argued that “The data in Table 2 teaches a skilled worker away from using a regimen consisting essentially of ravulizumab, because Huerta specifically notes that most of the CRs were attained when the patients were treated with PE, FPP, or heparin in addition to eculizumab therapy” but it is unclear what exactly applicant is arguing. To begin, apart from newly precented claim 41, all claims recite “comprising” which allows for, but does not require, an unlimited amount of additional, unrecited process steps to be performed on the patient in addition to that which is explicitly recited. Regarding claim 41, MPEP 2111.03(III) indicates that “The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention” and that absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." No specific definition of “consisting essential of” appears to be present in the instant specification. Further, in working example 1, it is disclosed that 6 of 8 patients received plasma exchange, 5 of 8 received dialysis, and all received a meningococcal vaccine in addition to being administered ravulizumab to treat p-aHUS (see most particularly page 48 of the instant specification). Thus it is unclear what therapeutic interventions applicant is trying to exclude from the instant claimed methods via the recitation of “consisting essentially of” since as discussed above the working example did more than simply administer ravulizumab to p-aHUS patients. Therefore, “consisting essentially of” has been interpreted as being equivalent to “comprising” consistent with the guidance set forth in MPEP 2111.03(III).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The rejection of claims 1-3, 5-11, 14, 16-18, and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,128,101 in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments as discussed earlier in section 6 of this office action.
Claims 1-3, 5-11, 14, 16-18, 34-35 and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,128,101 in view of Huerta et al.
The issued claims recite methods of administering anti-C5 antibodies comprising biological sequences matching those of the instant claims for the purpose of treating atypical hemolytic uremic syndrome at doses that match those recited in the instant claims concerning mass of drug per patient mass as well as timing intervals (see all issued claims, particularly independent claim 1). Such methods are also recited as being performed when the anti-C5 antibodies have the same Fc mutations as recited in the instant claims (see most particularly issued independent claim 2). The issued claims recite various clinical effects of the claimed administration methods, many of which are the same as those presently claimed including terminal complement inhibition (compare issued claim 12 to instant claim 18 for example). These teachings differ from the instant claimed invention in that the issued claims recite treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of treating aHUS as recited in the issued claims on p-aHUS patients. This is because the issued claims indicate their methods are generically useful in treating all forms of aHUS while Huerta et al. teach that anti-C5 antibodies had complete efficacy in treating p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patients of Huerta et al.
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant essentially argues that the grounds presented concerning why the teachings of Huerta et al. in combination with Shafner et al. are equally applicable to the instant rejection as the issued claims effectively replace the teachings of Shafner et al.
These arguments are not persuasive as has already been discussed earlier in this office action. See particularly section 7. It should be noted that as discussed in section 7, the phrase “consisting essentially of” has been interpreted as being equivalent to “comprising” as there is no specific guidance or definition for the term in relation to the claimed treatment methods in the specification and in view of the fact that working example 1 of the instant specification administered other therapies to the p-aHUS patients including 6 of 8 patients receiving plasma exchange, 5 of 8 receiving dialysis, and all receiving a meningococcal vaccine in addition to being administered ravulizumab. Additionally, it should be appreciated that the international application which published as WO 2019/084438 (i.e. “Shafer et al.”) entered the US national phase and eventually issued as patent 12,128,101.
The rejection of claims 1-3, 5-8, 18, and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9,107,861 in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments as discussed earlier in section 6 of this office action.
Claims 1-3, 5-8, 18, 34-35, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9,107,861 in view of Huerta et al.
The issued claims recite methods of administering anti-C5 antibodies comprising biological sequences matching those of the instant claims for the purpose of treating a patient afflicted with a C5 mediated complement condition, with atypical hemolytic uremic syndrome (aHUS) being explicitly recited (see all issued claims, particularly claims 1, 10, 11, 15, 16, and 18). Such methods are also recited as being performed when the anti-C5 antibodies have the same Fc mutations as recited in the instant claims (in particular compare issued claims 1 and 11 to instant claim 2). These teachings differ from the instant claimed invention in that the issued claims recite treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of treating aHUS as recited in the issued claims on p-aHUS patients. This is because the issued claims indicate their methods are generically useful in treating all forms of aHUS while Huerta et al. teach that anti-C5 antibodies had complete efficacy in treating p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patients of Huerta et al.
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant essentially argues that the grounds presented concerning why the teachings of Huerta et al. in combination with Shafner et al. are equally applicable to the instant rejection as the issued claims effectively replace the teachings of Shafner et al.
These arguments are not persuasive as has already been discussed earlier in this office action. See particularly section 7. It should be noted that as discussed in section 7, the phrase “consisting essentially of” has been interpreted as being equivalent to “comprising” as there is no specific guidance or definition for the term in relation to the claimed treatment methods in the specification and in view of the fact that working example 1 of the instant specification administered other therapies to the p-aHUS patients including 6 of 8 patients receiving plasma exchange, 5 of 8 receiving dialysis, and all receiving a meningococcal vaccine in addition to being administered ravulizumab.
The rejection of claims 1-3, 5-8, 18, and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,227,400 in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments as discussed earlier in section 6 of this office action.
Claims 1-3, 5-8, 18, 34-35, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,227,400 in view of Huerta et al.
The issued claims recite methods of administering anti-C5 antibodies comprising biological sequences matching those of the instant claims for the purpose of treating atypical hemolytic uremic syndrome (aHUS) wherein such antibodies also comprise the specific Fc mutations recited in instant claim 2 (see all issued claims, particularly claims 1-4). These teachings differ from the instant claimed invention in that the issued claims recite treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of treating aHUS as recited in the issued claims on p-aHUS patients. This is because the issued claims indicate their methods are generically useful in treating all forms of aHUS while Huerta et al. teach that anti-C5 antibodies had complete efficacy in treating p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patients of Huerta et al.
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant essentially argues that the grounds presented concerning why the teachings of Huerta et al. in combination with Shafner et al. are equally applicable to the instant rejection as the issued claims effectively replace the teachings of Shafner et al.
These arguments are not persuasive as has already been discussed earlier in this office action. See particularly section 7. It should be noted that as discussed in section 7, the phrase “consisting essentially of” has been interpreted as being equivalent to “comprising” as there is no specific guidance or definition for the term in relation to the claimed treatment methods in the specification and in view of the fact that working example 1 of the instant specification administered other therapies to the p-aHUS patients including 6 of 8 patients receiving plasma exchange, 5 of 8 receiving dialysis, and all receiving a meningococcal vaccine in addition to being administered ravulizumab.
The rejection of claims 1, 3, 5-8, 18, and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,584,164 in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments as discussed earlier in section 6 of this office action.
Claims 1, 3, 5-8, 18, 34-35, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,584,164 in view of Huerta et al.
The issued claims recite methods of administering anti-C5 antibodies comprising biological sequences matching those of the instant claims for the purpose of treating atypical hemolytic uremic syndrome (aHUS) (see all issued claims). These teachings differ from the instant claimed invention in that the issued claims recite treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant essentially argues that the grounds presented concerning why the teachings of Huerta et al. in combination with Shafner et al. are equally applicable to the instant rejection as the issued claims effectively replace the teachings of Shafner et al.
These arguments are not persuasive as has already been discussed earlier in this office action. See particularly section 7. It should be noted that as discussed in section 7, the phrase “consisting essentially of” has been interpreted as being equivalent to “comprising” as there is no specific guidance or definition for the term in relation to the claimed treatment methods in the specification and in view of the fact that working example 1 of the instant specification administered other therapies to the p-aHUS patients including 6 of 8 patients receiving plasma exchange, 5 of 8 receiving dialysis, and all receiving a meningococcal vaccine in addition to being administered ravulizumab.
The provisional rejection of claims 1-3, 5-11, 14, 16-18, and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-15, 18, 19, 27-34, 36, and 37 of copending Application No. 18/272,906 in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments as discussed earlier in section 6 of this office action.
Claims 1-3, 5-11, 14, 16-18, 34-35, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-15, 18, 19, 27-34, 36, and 37 of copending Application No. 18/272,906 in view of Huerta et al.
The copending claims recite the administration of anti-C5 antibodies comprising the same biological sequences as those recited in the instant claims to human patients to treat complement mediated TMA (thrombotic microangiopathy) including antibodies comprising the Fc mutations as recited in the instant claims (see all copending claims, and in particular compare instant claims 1-3 and 5 to copending claims 1-5 respectively). Dosing information concerning mass of drug per weight of patent as well as timing intervals are the same when comparing the instant and copending claims (compare in particular instant claim 9 to copending claim 9 as well as instant claim 11 to copending claims 12-14). Intended results of such administrations, such as reductions in free serum C5 concentration as well as terminal complement inhibition track when comparing the instant and copending applications (for example, compare instant claims 16 to copending claim 15 and instant claim 18 to copending claim 19). The copending claims differ from the instant claimed invention in that the copending claims do not teach that p-aHUS is a complement mediated thrombotic microangiopathy.
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of the copending claims on p-aHUS patients. This is because Huerta et al. teach that anti-C5 antibodies had complete efficacy in treating p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patients of Huerta et al.
This is a provisional nonstatutory double patenting rejection.
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant argues the copending application is later filed and cites MPEP 804(I)(B)(1)(b)(i) for its removal.
This argument is not persuasive as this NSDP rejection is NOT the only ground of rejection remaining in the instant application and thus the guidance of MPEP 804(I)(B)(1)(b)(i) is premature.
The provisional rejection of claims 1-3, 5-11, 14, 16-18, and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 60-79 of copending Application No. 19/014,677 in view of De Sousa Amorim et al. has been withdrawn in view of applicant’s claim amendments as discussed earlier in section 6 of this office action.
Claims 1-3, 5-11, 14, 16-18, 34-35, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 60-79 of copending Application No. 19/014,677 in view of Huerta et al.
The copending claims recite methods of administering anti-C5 antibodies comprising biological sequences matching those of the instant claims for the purpose of treating complement-associated conditions (see all copending claims, particularly claim 75). Disorders recited as being “complement-associated” include atypical hemolytic uremic syndrome (aHUS), HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count, a complication of pregnancy), spontaneous fetal loss, and recurrent fetal loss (see particularly claims 61 and 62). Doses of antibody based upon a patient’s body weight as well as timing of administrations track the limitations recited in the instant claims (for example compare copending claim 60 to instant claim 11). The copending claims recite various clinical effects of the claimed administration methods, many of which are the same as those presently claimed including terminal complement inhibition (compare copending claim 74 to instant claim 18 for example). These teachings differ from the instant claimed invention in that the copending claims recite treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Huerta disclose treatment of 10 women suffering from p-aHUS with the anti-C5 antibody eculizumab (see entire document, particularly the abstract and discussion sections as well as Table 1). Notably they disclose that plasmapheresis was unsuccessful in the majority of patients in contrast to the excellent responses to eculizumab in all patients thus treated (see particularly the fourth paragraph of the right column of page 456). Indeed, they report that eculizumab treatment was successful with normalization of all hematologic parameters and preservation of renal function in all 10 patients (see particularly the bottom of the right column of page 456 and Figure 2). They report that in 9 of the 10 women treated with eculizumab, the decision to begin eculizumab administration was made because of a lack of clinical response to plasma therapies (see particularly the first paragraph of the section titled “Treatment and evolution” on page 453). Administration of eculizumab is taught as beginning a median of 17 days post p-aHUS onset (so 50% earlier than day 17 and 50% later, see the section titled “Treatment and evolution” in the right column of page 453) with the majority of women developing p-aHUS one week or less following delivery(ibid and Figure 1). Huerta et al. teach that “As a whole, our study illustrates the complete efficacy of eculizumab to treat p-aHUS in 13 p-aHUS patients (2 were treated twice), without any adverse situations reported in any of them.” (see particularly the last sentence of the paragraph bridging pages 456 and 457).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of treating aHUS as recited in the copending claims on p-aHUS patients. This is because the copending claims indicate their methods are generically useful in treating all forms of aHUS while Huerta et al. teach that anti-C5 antibodies had complete efficacy in treating p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patients of Huerta et al.
This is a provisional nonstatutory double patenting rejection
Applicant's arguments filed June 22, 2026 have been fully considered but they are not persuasive. Applicant argues the copending application is later filed and cites MPEP 804(I)(B)(1)(b)(i) for its removal.
This argument is not persuasive as this NSDP rejection is NOT the only ground of rejection remaining in the instant application and thus the guidance of MPEP 804(I)(B)(1)(b)(i) is premature.
The following are new grounds of rejection necessitated by applicant’s claim amendments received June 22, 2026.
Claims 1-3, 5-11, 14, 16-18, 34-35, 40, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Shafner et al (WO 2019/084438, of record) in view of Delmas et al.
Shafner et al. disclose that antibodies that bind and neutralize C5 are to be administered to human patients to treat atypical hemolytic Uremic Syndrome (aHUS) as well as other thrombotic microangiopathies (see entire document, particularly the title, abstract, page 3, and claims). They disclose that the anti-C5 antibody named ravulizumab/ULTOMIRIS/ALXN1210/BNJ441 is particularly suitable for administration as part of their disclosed methods as it provides the advantage of binding C5 and preventing the cleavage of C5 into C5a and C5b thus preventing release of the proinflammatory mediator C5a and the formation of the pore-forming membrane attack complex (see for example lines 17-32 of page 3, lines 19-30 of page 20, and the claims). It should be noted that the biological sequences recited in the instant claims are the same sequences present in ravulizumab (see particularly the admission by applicant from line 19 of page 20 to line 7 of page 21 of the instant specification). The administered anti-C5 antibodies are disclosed as having the same binding affinities as those recited in the instant claims (compare lines 11-16 of page 4 as well as claims 10 and 11 to the text of instant claims 6 and 7). Such administered antibodies are further disclosed as comprising Fc mutations including M428L and N434S per EU numbering (see for example pages 3 and 4) and as being administered intravenously (see for example page 33 as well as claim 21). Indeed, ravulizumab is disclosed as being an improved variant of eculizumab which comprises 4 substitution mutations and which has an extended half-life as compared to the parental antibody (see particularly page 61, as well as Table 22 The dosing information, including both mass of drug as well as the timing of administration are the same when comparing the teachings of Shafner to that which is presently claimed (compare claims 1 and 2 to instant claims 9 and 10, and claims 12-14 to instant claim 11). Continued administration out to two years is also taught (compare claim 20 to instant claim 17). Conditions other than aHUS disclosed as amenable to treatment via the methods of Shafner et al. include HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count, a complication of pregnancy), spontaneous fetal loss and recurrent fetal loss (see particularly page 44). These teachings differ from the instant claimed invention in that Shafner et al. disclose treating aHUS generically and do not appear to specify the subgenus of pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS).
Delmas et al. disclose administering eculizumab to a post-partum atypical hemolytic-uremic syndrome patient (see entire document, particularly the title). Notably, the woman was admitted to the hospital 7 says after delivery and received eculizumab 3 days post admission (see particularly the second and third paragraphs as well as Figure 1), and thus antibody administration began in the range of 5-11 days after delivery. Plasma exchange in addition to eculizumab administration was performed on the patient (ibid). The patient was a known carrier for mutations in factors H and I, and had a familial history of aHUS. Eculizumab is disclosed as being administered at 900 mg at the start of treatment as well as higher doses at 1200 mg (see Figure 1 for timing of such doses). The patient responded positively to treatment, was tapered off the antibody drug at 18 months, and showed no signs of aHUS at the two month follow-up after stopping eculizumab (see particularly the left column of page 244).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of treating aHUS disclosed by Shafner et al on p-aHUS patients. This is because Shafner et al. teach their methods are generically useful in treating all forms of aHUS while Delmas et al. specifically teach that the anti-C5 antibody eculizumab induces terminal complement blockade and successfully treated a p-aHUS patients. Artisans would have a reasonable expectation of success in doing so given the favorable response to anti-C5 treatment in the p-aHUS patient of Delmas et al. and the expected advantages of ravulizumab which include binding C5 and preventing the cleavage of C5 into C5a and C5b thus preventing release of the proinflammatory mediator C5a and the formation of the pore-forming membrane attack complex as well as improved half-life as compared to eculizumab.
It should be noted that newly presented independent claim 41 recites that the claimed method “consists essentially of” administering ravulizumab. As discussed earlier in this office action in greater detail, this transitional phrase has been interpreted as being equivalent to “comprising” as there is no specific guidance or definition for the term in relation to the claimed treatment methods in the specification and in view of the fact that working example 1 of the instant specification administered other therapies to the p-aHUS patients including 6 of 8 patients receiving plasma exchange, 5 of 8 receiving dialysis, and all receiving a meningococcal vaccine in addition to being administered ravulizumab. See also MPEP 2111.03(III).
In view of all of the above, the prior art provides guidance, direction, and an expectation of success in selecting p-aHUS as a specific patient subpopulation to be treated within the larger genus of all aHUS as is taught by Shafner et al.
Claims 1, 3, 5-8, 18, 34-35, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12,617,846 in view of Shafner et al (WO 2019/084438, of record) and in view of Delmas et al.
The issued claims recite administering an antibody with the same CDRs as ravulizumab (claim 1) including ravulizumab itself (see for example claims 13 and 20) to a human patient to treat a complement-associated condition (see all issued claims). Notably, issued claim 17 recites that p-aHUS is a complement-associated condition treated by the claimed methods. Intravenous administration is recited (see for example issued claim 3) as are various expected outcomes of such an administration, including terminal complement inhibition (see issued claim 18). Such claims differ from the instant claimed invention in that the issued claims do not specify that the administration for p-aHUS takes place no more than 15 says following delivery of the baby.
Shafner et al. disclose that antibodies that bind and neutralize C5 are to be administered to human patients to treat atypical hemolytic Uremic Syndrome (aHUS) as well as other thrombotic microangiopathies (see entire document, particularly the title, abstract, page 3, and claims). They disclose that the anti-C5 antibody named ravulizumab/ULTOMIRIS/ALXN1210/BNJ441 is particularly suitable for administration as part of their disclosed methods as it provides the advantage of binding C5 and preventing the cleavage of C5 into C5a and C5b thus preventing release of the proinflammatory mediator C5a and the formation of the pore-forming membrane attack complex (see for example lines 17-32 of page 3, lines 19-30 of page 20, and the claims). It should be noted that the biological sequences recited in the instant claims are the same sequences present in ravulizumab (see particularly the admission by applicant from line 19 of page 20 to line 7 of page 21 of the instant specification). The administered anti-C5 antibodies are disclosed as having the same binding affinities as those recited in the instant claims (compare lines 11-16 of page 4 as well as claims 10 and 11 to the text of instant claims 6 and 7). Such administered antibodies are further disclosed as comprising Fc mutations including M428L and N434S per EU numbering (see for example pages 3 and 4) and as being administered intravenously (see for example page 33 as well as claim 21). Indeed, ravulizumab is disclosed as being an improved variant of eculizumab which comprises 4 substitution mutations and which has an extended half-life as compared to the parental antibody (see particularly page 61, as well as Table 22 The dosing information, including both mass of drug as well as the timing of administration are the same when comparing the teachings of Shafner to that which is presently claimed (compare claims 1 and 2 to instant claims 9 and 10, and claims 12-14 to instant claim 11). Continued administration out to two years is also taught (compare claim 20 to instant claim 17). Conditions other than aHUS disclosed as amenable to treatment via the methods of Shafner et al. include HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count, a complication of pregnancy), spontaneous fetal loss and recurrent fetal loss (see particularly page 44).
Delmas et al. disclose administering eculizumab to a post-partum atypical hemolytic-uremic syndrome patient (see entire document, particularly the title). Notably, the woman was admitted to the hospital 7 says after delivery and received eculizumab 3 days post admission (see particularly the second and third paragraphs as well as Figure 1), and thus antibody administration began in the range of 5-11 days after delivery. Plasma exchange in addition to eculizumab administration was performed on the patient (ibid). The patient was a known carrier for mutations in factors H and I, and had a familial history of aHUS. Eculizumab is disclosed as being administered at 900 mg at the start of treatment as well as higher doses at 1200 mg (see Figure 1 for timing of such doses). The patient responded positively to treatment, was tapered off the antibody drug at 18 months, and showed no signs of aHUS at the two month follow-up after stopping eculizumab (see particularly the left column of page 244).
Therefore, it would have been obvious to an artisan at the time of filing to practice the methods of the issued claims for treating p-aHUS by administering ravulizumab in the timeframe of 15 or fewer days from delivery, including 5-11 days post-delivery. This is because Delmas et al. specifically teach that the anti-C5 antibody eculizumab when administered in this timeframe was successful in treating p-aHUS, and as per Shafer et al. ravulizumab is an improved version of eculizumab offering advantages including increased half-life as compared to the parental eculizumab antibody.
It is appreciated that the newly presented independent claim 41 recites that the claimed method “consists essentially of” administering ravulizumab. As discussed earlier in this office action in greater detail, this transitional phrase has been interpreted as being equivalent to “comprising” as there is no specific guidance or definition for the term in relation to the claimed treatment methods in the specification and in view of the fact that working example 1 of the instant specification administered other therapies to the p-aHUS patients including 6 of 8 patients receiving plasma exchange, 5 of 8 receiving dialysis, and all receiving a meningococcal vaccine in addition to being administered ravulizumab. See also MPEP 2111.03(III). Thus, while it is clear that ravulizumab must be administered, it is unclear what cannot be administered as per the claimed method give that additional active agents and procedures were performed in the working example on p-aHUS such that “consisting of” language wherein everything apart form ravulizumab is excluded is not reasonably commensurate in scope with that which applicant has demonstrated to work per said examples in the specification.
No claims are allowable.
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 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.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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