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 .
1. Election of Species
This application contains claims directed to the following patentably distinct species (Applicants are to elect one from each of (a) and (b)) –
(a) Claim 29 – one antibody
(b) Claim 33 – one condition
The species are independent or distinct because each sequence would require its own potentially non-overlapping search. In addition, these species are not obvious variants of each other based on the current record. Therefore, there is a search and/or examination burden for the patentably distinct species as set forth above.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no
generic claim is finally held to be allowable. Currently, all claims are generic.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
2. Election by Telephone
During a telephone conversation with Jill Gorny Sloper on November 10, 2025 Applicants elected the species of crovalimab and PNH.
3. Additional Information
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species or invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention or species may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected invention or species.
Should applicant traverse on the ground that the inventions have unity of invention (37 CFR 1.475(a)), applicant must provide reasons in support thereof. Applicant may submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. Where such evidence or admission is provided by applicant, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other invention.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
4. Formal Matters
Claims 1-30, 32, 33 and 36, drawn to crovalimab and PNH, are pending and are the subject of this Office Action.
5. Specification
A. If applicable, the first line of the specification should be updated to reflect the status (e.g. “now U.S. Patent No.”, or “now abandoned”) of any parent applications. Similarly, any U.S. or Foreign Applications cited in the specification which have since issued should be updated with the corresponding Patent No.
B. The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicants’ cooperation is requested in correcting any errors of which Applicants may become aware.
6. Claim Objections
A. Claim 1 is objected to since “complement mediated” should be hyphenated.
B. Claim 22 is objected to since, in part (a), it is believed that part (a) should recite “40≤” or “≥40”.
C. Claim 29 is objected to since it is unclear why the generic names “tesidolumab” and “crovalimab” are capitalized.
7. Claim Rejections - 35 USC § 112(b)
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.
A. Claim 9 recites the limitation "the threshold value". There is insufficient antecedent basis for this limitation in the claim. It is believed that this term is intended to be synonymous with “level” in claim 1; however, it is suggested amending one claim or the other, or to provide further details as to why two terms are used.
B. Regarding claim 11, the phrase "for example" (“e.g.”) renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
C. Regarding claim 15, the phrase "such as" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
D. Claims 18, 23 and 29 contains the trademark/trade name SOLIRIS®, ULTOMIRIS® and ELIZARIA®, respectively. According to MPEP 2173.05(u), where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a type of antibody and, accordingly, the identification/description is indefinite.
8. 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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-19, 21, 22, 24, 28, 30, 33 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Cone et al. (British Journal of Haematology; cited on the PCT/ISA/210 submitted 4/20/23; copy not provided herewith).
The invention is essentially drawn to treating a patient with a combination of anti-C5 antibodies, or replacing one with another. The invention focuses on measuring the multivalent immune complexes formed when both antibodies bind C5 and adjusting an antibody dose accordingly.
Cone teaches the following -
When considering development of therapeutic monoclonal antibodies, it is essential to account for the properties of the circulating immune complexes formed with the target antigen. In particular, the valency of such complexes can affect clearance, effector function and uptake by phagocytic cells involved in antigen processing and inflammation. Therefore, significant care and consideration must be given to when a recipient is exposed to more than one immunoglobulin G (IgG) antibody which bind to a monovalent target at different sites, potentially leading to formation of multivalent immune complexes. For example, this could arise when a patient being treated with one anticomplement component 5 (C5) IgG is switched to a differentanti-C5 IgG that binds to a different site on C5, wherein finite levels of the first antibody remain in circulation to maintain continuous pharmacodynamic C5 suppression.
Cone additionally teaches the use of eculizumab, a humanized monoclonal therapeutic antibody (meeting claims 15, 16 and 18), as well as ravulizumab (claims 19, 28), for the treatment of PHN and aHUS patients (both recited in claim 33. Other claims reciting these disorders are discussed in subsequent rejections under 35 USC 103).
Therefore, Cone teaches the crux of the instant invention. The only essential differences are that Cone does not teach obtaining a patient sample, nor determining a threshold level as required in independent claims 1, 2 and 4, as well as dependent claim 5. However, given the teachings of Cone regarding the potential risk to patients of using two antibodies, it would have been obvious at the time to have taken appropriate routine biological samples (see also claim 13) during treatment as well as to have identified and to not have exceeded a predetermined threshold in order to minimize the formation of multivalent immune complexes (claim 36). Regarding claims 3 and 4, it would have also been obvious that, if the artisan (e.g. physician) intended to switch antibodies, that, in order to maintain therapeutic effect during the transition, the levels of antibodies should be measured, using this threshold level as a guide, while weaning off the undesired antibody (claim 3) and that, if the level is exceeded, the dose of one of the antibodies should be reduced for an appropriate until the levels return to below the threshold (claim 14). Cone teaches that these measurements can be made using MALS, meeting instant claim 12. The recited teachings, above, from Cone also meet claim 17 with regard to antibodies which bind different epitopes or do not compete for binding.
Regarding claims 6-8, 10, 19, 21, 22 and 24, given the fact that two antibodies performing essentially the same function by targeting the same protein are being used simultaneously, along with the knowledge that complexes are potentially dangerous and are to be avoided it would have been obvious to have optimized the dosage, including starting the second antibody at a sub-therapeutic dose in order to reduce the risk of side effects. This would involve adjusting the dosing schedule. [W]here the general conditions of a claim are disclosed in the prior art), it would not have been inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”). Furthermore, claim 36 would have been obvious since treatment without toxicity is a major goal of any treatment plan.
Regarding claims 9-11, since Cone teaches that other non-competitive antibodies are to be studied, it would flow that the two antibodies would bind to a single molecule of complement C5 (see also third paragraph of Cone) and that, in order to reduce side effects while maintaining a therapeutic advantage, the proper stoichiometry of the two different antibodies should be determined. See also In re Aller.
B. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Cone et al. in view of Lee et al. (cited as reference 11 on one of the 8-page IDS’s). The teachings of Cone are seen in paragraph A, above. Cone does not teach the specific regimen in claim 20. However, Lee does (page 531, top of right column).
C. Claims 23, 25 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Cone et al. in view of Shafner et al. (WO 2019/084438; cited on the ISA/PCT/210 submitted 4/20/23 and on the 10-page IDS filed 1/26/24). The teachings of Cone are seen in paragraph A, above. Cone does not teach the antibodies of instant claim 23, nor the dosing regimen. However, claim 1 of Shafner essentially teaches these limitations. Cone does not teach IV administration as recited in instant claim 32. However, claim 21 of Shafner does.
D. Claims 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Cone et al. in view of Tanaka et al. (reference 41 on one of the 8-page IDS’s filed 1/26/24). The teachings of Cone are seen in paragraph A, above. Cone does not teach treatment of pediatric patients (claim 26), nor the specific dosing schedule of claim 27 for either one of the antibodies. However, Tanaka teach this schedule for ravulizumab (Figure 1).
E. Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Cone et al. in view of Roth et al. (Blood (2020); cited on the PCT/ISA/210 submitted 4/20/23 and on one of the 8-page IDS’s filed 1/26/24).
The teachings of Cone are seen in paragraph A, above. Cone does not teach crovalimab. Howver, Roth teaches that “Subcutaneous crovalimab (680 mg; 4 mL), administered once every 4 weeks, provides complete and sustained terminal complement pathway inhibition in patients with PNH”.
In re Kerkhoven (205 USPQ 1069, CCPA 1980) summarizes:
"It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for the same purpose in order to form a combination that is to be used for the very same purpose: the idea of combining them flows logically from their having been individually taught in the prior art."
9. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647