Office Action 2: Notice of Allowance (2025-02-25)

CLAIMS:
IN THE CLAIMS:

Set forth below in ascending order, with status identifiers, is a complete listing of all

claims currently under examination. Changes to any amended claims are indicated by \[\[double

brackets\]\], and/or underlining. This listing also reflects any cancellation and/or addition of claims.

1\. (Currently Amended) A method for determining aneffective dose of a multi-Fc therapeutic comprising:(a) administering the multi-Fc therapeutic to a subject in need thereof at a starting dose ofthe multi-Fc therapeutic;
(b) determining lood iC3b level of he subject;
(c) determining that the subject requires a first cumulative escalated dose of the multi-Fc therapeutic if the subject has been determined to have:(i) a\_blood iC3b levels lower than a predetermined threshold following administration with the starting dose of the multi-Fc therapeutic; or (ii) a\_blood iC3b levels with a change percent of less than 10%, less than 20%, less than 30%, less than 0%, or less than 50% from baseline; and
(d) administering a first cumulative escalated dose of the multi-Fc therapeutic,
wherein the multi-Fc therapeutic comprises a-multimers of a homodimer and wherein the homodimer comprises a monomer comprising amino acids 21-264 of SEQ ID NO:4.

2\. (Currently Amended) The method of claim 1, further comprising:(e) repeating the determination of thea-blood iC3b level of the subject after administration of the first cumulative escalated dose of the multi-Fc therapeutic; and
(f) administering a second cumulative escalated dose of the multi-Fc therapeutic that is higher than the first cumulative escalated dose if the subject is determined to have:
(i) a blood iC3b levels lower than a predetermined threshold following administration with the starting dose of the multi-Fc therapeutic; or (ii) a blood iC3b level with a change percent of less than 10%, less than 20%, less than 30%, less than 0%, or less than 50% from baseline.

3\. (Currently Amended) The method of claim 1, wherein the etermination of blood iC3b levels is repeated with continued cumulative escalated doses of the multi-Fc therapeutic until the predetermined threshold ofblood iC3b level is met, or until the blood iC3b levels hasve changed by greater than 10%.

4\. (Currently Amended) The method of claim 1, wherein the first cumulative escalated dose of the multi-Fc therapeutic is at least 105% of the starting dose of said multi-Fc therapeutic.

5\. (Currently Amended) The method ofclaim 1, wherein administering a cumulative escalated dose comprises administering an escalated dose of the multi-Fc therapeutic throughout the dosing period.

6\. (Original) The method of claim 1, wherein administering a cumulative escalated dose comprises administering both an escalated dose and an incremental dose during the dosing period.

7\. (Currently Amended) The method of claim 1, wherein the cumulative escalated dose of the multi-Fc therapeutic is at least 110%, 115%, 120%, 125%, 150%, 175%,- or 200% of the previously administered dose of said multi-Fc therapeutic.

8\. (Currently Amended) The method of claim 1, wherein the predetermined threshold of blood iC3b level is 25 pag/mnL to 300 pag/mL, 0 pag/mnL to 200 pag/mL, 75 pag/mnL to 125 pag/mL, or 100 pag/mL.

9\. (Currently Amended) The method of claim 1, wherein the predetermined threshold of blood iC3b level is 25% of neutrophils and monocytes that are iC3b+.

10\. (Currently Amended) The method of claim 1, wherein the predetermined threshold of blood iC3b level is an iC3b mean fluorescence intensity (MFI) of 125% of the baseline iC3b MFI.

11\. (Currently Amended) The method of claim 1, wherein the percent change is less than 10%.

12\. (Currently Amended) The method of claim 1, wherein the blood iC3b level is determined by measurement of a surrogate marker for iC3b.

13\. (Original) The method of claim 12, wherein the surrogate marker for iC3b is selected from the group consisting of iC3bl, iC3b2, C3a, C3a desArg, C4a, C4a desArg, C3f, C3dg, C3d, C3g and a combination thereof.

14\. (Original) The method of claim 12, wherein the surrogate marker for iC3b is C3a or C4a.

15\. (Currently Amended) The method ofclaim 12, wherein the predetermined threshold for the surrogate marker of iC3b is less than 30 ng/mL, less than 20 ng/mL, less than 10 ng/mL or less than 5 ng/mL.

16\. (Currently Amended) The method of claim 12,wherein the percent change of the surrogate marker is less than 10%, less than 20%, less than 30%, less than 40%, or less than 50%.

17\. (Currently Amended) The method of claim 1, wherein the subject has an autoimmune or inflammatory disease, wherein the autoimmune or inflammatory disease is selected from thea group consisting of autoimmune cytopenia, idiopathic thrombocytopenic purpura (ITP),

rheumatoid arthritis, systemic lupus erythematosus, asthma, Kawasaki disease, Guillain-Barre syndrome, Stevens-Johnson syndrome, Crohn''s colitis, diabetes, chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis, anti-Factor VIII autoimmune disease, dermatomyositis, vasculitis, uveitis, and Alzheimer"s disease.

18\. (Currently Amended) The method of claim 1, wherein the blood iC3b level is determined by an immunoassay.

19\. (Original) The method of claim 18, wherein the immunoassay comprises an ELISA or a western blot.

20\. (Currently Amended) The method of claim 1, wherein the blood iC3b level is determined by flow cytometry.

OFFICE 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 .
EXAMINER'S COMMENT
2.	The amendment/argument filed 12/10/2024, has been entered.
Any comments considered necessary by applicant must be submitted no later than the payment of the Issue Fee and, to avoid processing delays, should preferably accompany the Issue Fee. Such submissions should be clearly labeled Comments on Statement of Reasons for Allowance.
Conclusion
4.	Claims 1-20 have been allowed.
5.

APPLICANT REBUTTAL: REMARKS
Upon entry of these amendments, claims 1-20 are pending in the present application. In this response, claims 1-5, 7-12, 15-18, and 20 have been amended to improve clarity. Support for the claim amendments can be found throughout the application as originally filed. No new matter is added. Entry and consideration are respectfully requested.
Amendment and cancellation of certain claims is not to be construed as a dedication to the public of any of the subject matter of the claims as previously presented.
Claim Rejections - 35 U.S.C.  S112
Claims 1-4, 7-11 and 15-16 stand rejected under 35 U.S.C. §112(b) or 35 U.S.C. §112 (pre- AIA), second paragraph, as allegedly being indefinite for reciting the term "about." Office Action, pages 2-3.
Without acquiescing to the propriety of the rejection and solely in an effort to expedite prosecution, claims 1-4, 7-11 and 15-16 have been amended to remove the term "about", thus rendering this rejection moot.
Claim Rejections - 35 U.S.C.  S103
Claims 1-20 stand rejected under 35 U.S.C. §103 as being unpatentable over Block et al. (WO 2012016073, published on February 2, 2012, ("Block")) in view of Olson et al. (U.S. Publication No. 2012-03 15266, published on December 13, 2012, ("Olsen")). Office Action, pages 3-5.
The present claims are directed to a method for determining an effective dose of a multi- Fc therapeutic comprising: (a) administering the multi-Fc therapeutic to a subject in need thereof at a starting dose of the multi-Fc therapeutic; (b) determining the blood iC3b level of the subject;
(c) determining that the subject requires a first cumulative escalated dose of the multi-Fc therapeutic if the subject has been determined to have: (i) a blood iC3b level lower than a
predetermined threshold following administration with the starting dose of the multi-Fc therapeutic; or (ii) a blood iC3b level with a change percent of less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% from baseline; and (d) administering a first cumulative escalated dose of the multi-Fc therapeutic, wherein the multi-Fc therapeutic comprises multimers of a homodimer and wherein the homodimer comprises a monomer comprising amino acids 21- 264 of SEQ ID NO:4. By utilizing blood iC3b levels as a marker, the present method enables the determination of the maximally effective dose of the multi-Fc therapeutic with the minimum amount of the therapeutic, thereby reducing adverse effects of overdosing and minimizing therapeutic waste. See paragraph [0009] of the present application.
Neither Block nor Olson teaches or suggests utilizing iC3b as a marker to determine the maximally effective dose of the multi-Fc therapeutic. Block teaches multimerizing stradomers, including homodimeric stradomer units comprising monomers of SEQ ID NO: 4. However, Block fails to teach strategies for determining the maximally effective dose of the multi-Fc therapeutic and is completely silent on the relevance of iC3b for such methods.
Olson is directed generally to methods of detecting iC3b. See e.g., paragraph [0008] of Olson. There is nothing in Olson that provides any teaching or suggestion that iC3b levels can be used to determine the appropriate dose of the multi-Fc therapeutic. Olson describes detection of iC3b and subsequent modification of a subject's treatment regimen to
decrease
pathologic complement activation. See paragraph [0131] of Olson, which states "Accordingly, the clinician may then modify the individual's treatment by increasing the dosage of medications, such as anti- inflammatory agents or complement inhibitors, until a desired
stabilization or decrease in complement activation
levels is achieved." See also Olson at paragraph [0117], which describes determining a level of iC3b in a subject, wherein a detection level above a threshold of iC3b indicates that the subject is suffering from or susceptible to
undesirable and/or patholo
gic
complement activation.
See also paragraph [0112] of Olson which states that the concentration of iC3b correlates to a severity of inflammatory distress. Treatment is then administered to
decrease
the undesired complement activation. This is directly counter to the teachings of the present application.
In particular, paragraph [0043] of the present application states that, in contrast to the teachings of Olson, the data provided in the present application indicates that higher levels of iC3b are
desirable
in the treatment of autoimmune and inflammatory disorders. Therefore, the present methods generally utilize iC3b to determine that a sufficient level of
complement activation
has occurred in order to achieve a desired therapeutic effect. See paragraphs [0039] and [0043] of the present application. Increasing doses of the multi-Fc therapeutic are administered until a sufficient
increase
in iC3b levels has occurred to indicate that the subject is responsive to the multi-Fc therapeutic. Olson describes the exact opposite - i.e., adjusting medication until a
decrease
in complement activation is achieved. See paragraph [0117] of Olson.
For at least the foregoing reasons, Applicant submits that the present claims are not obvious over Block in view of Olson and respectfully requests withdrawal of this rejection under 35 U.S.C. § 103.
Double Patenting
Claims 1-20 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as allegedly being unpatentable over claims 157-171 of copending Application No. 17/400,367 (now issued as US patent 12,084,482) ("the '367 application") in view of Olson. Office Action, pages 5-7.
A nonstatutory double patenting rejection made under the obviousness analysis should make clear "the reasons why a person of ordinary skill in the art would conclude that the invention defined in the claim at issue would have been an obvious variation of the invention defined in a claim in the patent." MPEP 804(II)(B)(3). The '367 application is a divisional application of the US national phase of Block. As discussed above, neither Block nor Olson teaches or suggests utilizing iC3b as a marker to determine the maximally effective dose of the multi-Fc therapeutic as presently claimed.
As a first point, and as the Examiner admits, the '367 application "do[es] not teach determining the level of iC3b." Office Action, page 7.
Secondly, and as discussed above, Olson fails to teach or suggest that iC3b levels can be used to determine the appropriate dose of the multi-Fc therapeutic. In fact, the teachings of Olson are counter to that of the present application. Olson teaches iC3b measurements as an indicative of
patholo
g
ic complement activation
and modification of a subject's treatment in order to
decrease
said complement activation. In contrast, the present application teaches iC3b measurements as indicative of
desirable complement activation
and increasing of a treatment dose of the multi-Fc therapeutic until a sufficient
increase
in iC3b levels and complement activation has occurred.
For at least the foregoing reasons, Applicant submits that the combination of the '367 application and Olson is not appropriate for a nonstatutory double patenting rejection. Applicant therefore respectfully requests withdrawal of this rejection.
CONCLUSION