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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 17, 2025 has been entered.
Claims 163, 165-166, 168, and 173-178 are under consideration in this office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 17, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
Modified Rejection
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.
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.
Claims 163, 165-166, 168, and 173-178 are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0210801A1, published July 27, 2017 (“Kim”; PTO-892 from 5/22/24) in view of Wang et al (PTO-892 from 5/22/24), Fasanmade et al, published September 16, 2009 (see instant PTO-892), and US 2018/0291101A1 (“Blumberg”; PTO-892 from 5/22/24).
Kim teaches anti-FcRn antibodies and compositions thereof for the treatment of autoimmune disease (see abstract). The anti-FcRn antibody of Kim is comprised of HCDR1-3 of SEQ ID NOs: 27-29 [0088], LCDR1-3 of SEQ ID NOs: 30-32 [0094], heavy chain variable region of SEQ ID NO: 6, and a light chain variable region of SEQ ID NO: 16 [0102]. These amino sequences are identical to HCDR1-3, LCDR1-3, heavy chain variable region, and light chain variable region of claims 163 and 165 (same SEQ ID NOs), as in the antibody of instant claim 163.
The pharmaceutical composition of the anti-FcRn antibody of Kim may be applied for the treatment or amelioration of autoimmune disease mediated by IgG and FcRn, including autoimmune Grave’s disease ([0119], [0122]), as in instant claim 163. In the method of Kim, the antibody may be administered at a dose of 1 mg/kg to 2 g/kg [0120], or more preferably 1-40 mg/kg [0122]. The weight-based dose of 1-40 mg/kg of Kim can be converted to a fixed dose using a conversion factor of 80, as the median body weight for adults is approximately 80 kg, as evidenced by Walpole et al (PTO-892 from 5/22/24). When converted to a flat dose, the dosage range of Kim is 80-3200 mg; this range of dosages overlaps with the dosages of 650-750 mg anti-FcRn antibody, as in claim 163.
The antibody of Kim may be delivered subcutaneously [0122], as in instant claim 166. The composition of Kim may be administered once a week or once every two weeks [0246], as in claim 168.
Kim teaches that the antibody HL161B is comprised of HCDR1-3 of SEQ ID NOs: 27-29 and LCDR1-3 of SEQ ID NOs: 30-32 (Table 2), which are the same six CDRs of the antibody of instant claim 163 (same SEQ ID NOs). As shown in Figure 6a, treatment of HL161B reduces IgG in serum by 40-70%, as required by claims 174 and 177-178.
Regarding claims 175-176, while Kim is silent on the intended results of the effect of the anti-FcRn antibody on reduction in anti-TSHR IgG or anti-IGF-1R IgG in patients with Graves’ ophthalmopathy, it is clear that the same patient population treated with the same antibody would have the same characteristics and effects as the instantly claimed antibody since there is no evidence to the contrary. Note that rejections for anticipation or obviousness are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not the same.
Although Kim teaches the claimed anti-FcRn antibody and methods for reducing IgG in serum and treating autoimmune disease complement activation in a subject, Kim does not explicitly teach a method for treating Graves’ ophthalmopathy, as required by instant claim 163. However, it would have been obvious to one of ordinary skill in art that a method of reducing IgG in serum in a subject suffering from elevated IgG that contributes to the pathogenesis of disease could also be applied to Graves’ ophthalmopathy. Based on the teachings of Kim, the ordinary artisan would immediately envision the treatment of other disorders associated with elevated IgG in serum, and it would be obvious that treatment with the same anti-FcRn antibody for one disease would be applicable to another disease associated with the same defect; applying a known technique to a known disease ready for improvement will yield predictable results (see MPEP 2143).
To support further the obviousness of treating a patient with Graves’ ophthalmopathy with the claimed anti-FcRn antibody, Blumberg teaches anti-FcRn antibodies that block the binding of FcRn to IgG Fc for the treatment or prevention of antibody-mediated autoimmune disorders ([0002], [0119]), including Graves’ ophthalmopathy [0054]. Blumberg teaches that the anti-FcRn antibody may be administered in combination with other agents, drugs, or hormones [0269], as in claim 173.
Given that Kim teaches the claimed antibody for the treatment of Graves’ disease and that Blumberg teaches anti-FcRn antibodies for the treatment and prevention of Graves’ ophthalmopathy, it would have been obvious to the ordinary artisan to treat patients with Graves’ ophthalmopathy with the anti-FcRn antibody of Kim. One would do so with a reasonable expectation of success because Blumberg has already expressly contemplated the use of another anti-FcRn antibody for the treatment of the same disease. Substituting one known element for another to yield predictable results does not meet the threshold for a prima facie case of obviousness, absent convincing evidence to the contrary.
Further concerning the flat dose of claim 163, Wang et al (p 1023, col 2, para 2) describes advantages for treating patients with a fixed dose versus body size-based dosing when using monoclonal antibodies. These advantages include ease of dose preparation, reduced cost, and reduced chance of dosing errors (pg 1023, “Conclusion”). Wang et al teaches that body size-based dosing and fixed dosing performed similarly for the 12 monoclonal antibodies evaluated (pg 1023, “Conclusion”). These teachings of Wang, as argued by applicant in the Remarks filed 10/17/2025, fail to address substantively why one of ordinary skill in the art would have used fixed dosing for an anti-FcRn antibody (pg 8).
As taught by Fasanmade et al., the availability of two randomized clinical trials in the same patient population allowed a thoroughly developed population pharmacokinetic (PK) analysis of the monoclonal antibody therapy infliximab in patients with ulcerative colitis. A two-compartment PK model provided reliable PK parameter and covariate effect estimation for infliximab (pg 1221). Fasanmade et al uses population pharmacokinetics for Infliximab concentration-time data analysis using the program NONMEM (see abstract, pg 1213). Fasanmade et al teaches univariate models including weight on CL (clearance), weight on V2 (volume of distribution for the peripheral compartment) and weight on V1 (volume of distribution for the central compartment). Table 4 shows the impact of some of the covariates on the OFV of population PK model when each covariate was tested on each of the PK parameters. Fasanmade et al. teaches that it is apparent from the final model that body size is an important determinant of infliximab exposure. Body weight influences V1 (with a power factor of 0.54) but not CL. Fasanmade et al teaches that a body weight-adjusted dosing (as is approved for infliximab) is necessary to allow equivalent exposure among all patients to mitigate a possible weight-related influence of infliximab exposure (pg 1223). Thus, Fasanmade demonstrates that the ordinary artisan was aware of the criteria that determine success with a flat dose and that the choice between flat or weight-based dose is dependent on the PK behavior of each monoclonal antibody.
Given that Kim teaches the claimed antibody and related dosages and Wang et al and Fasanmade et al teach methods for determining Immunologically effective doses for antibody therapy, it would have been obvious to one of ordinary skill in the art to apply a fixed dose as taught by Wang et al and Fasnmade to the anti-FcRn antibody Kim, because Wang along with Fasanmade demonstrate that not only were the criteria for flat dosing known in the art, it was known that these criteria had been met for several other antibodies. Given the combined teachings of Kim, Wang, and Fasanmade, the ordinary artisan would have reasonably expected to have identified a flat dose within the recited range of 650-750 mg of instant claim 163. The identification of a dose within the broad range of Kim could have been achieved through routine optimization because the concentration of antibody is a result effective variable, which can be routinely determined and optimized in the pharmaceutical arts. It would have been routine for a person of ordinary skill in the art to verify the expectation that a specific dosage using the population pharmacokinetics model of Fasanmade et al within a previously suggested dosage range taught in Kim would have been safe and effective in the treatment of a Graves’ ophthalmopathy, as taught by Blumberg. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP §§ 2144.05 part II.A. The determination of the exact doses in view of the patient’s conditions is well within the skill of those skilled artisans. Further, it is well settled that "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). It would be conventional and within the skill of the art to identify and determine the optimum dose and timing of administration protocols to treat Graves’ ophthalmopathy.
When other methods similar to a claimed method have been successful, the court has determined there would have been a reasonable expectation of success. For example, in Velander v. Garner, 348 F.3d 1359, 1379 (Fed. Cir. 2003), a reasonable expectation of success was found for a method of producing a particular protein when several other proteins had been produced in a similar way.
Response to Amendment
The affidavit under 37 CFR 1.132 filed October 17, 2025 (“Tedeschi Declaration”) is insufficient to overcome the rejection of claims 163, 165-166, 168, and 173-17 based upon the combined teachings of Kim and Blumberg under 35 U.S.C. 103 as set forth in the last office action; reasons are addressed below in the response to arguments.
Response to Arguments
Applicant's arguments filed October 17, 2025 have been considered.
Applicant asserts that the dose range provided by Kim (1 mg/kg to 2 g/kg or preferably 1-40 mg/kg) is so broad that it does not provide any actionable guidance on selecting a starting dose of the claimed anti-FcRn antibody for optimization (remarks, pg 8). Applicant submitted a Declaration by Dr. Philip Tedeschi that evaluated the efficacy of antibody RVT-1401 for treating thyroid eye disease (TED) (remarks, pg 6). A dose of 680 mg demonstrated superior efficacy compared to doses of 340 mg or 225 mg (remarks, pg 6), and applicant argues that this superior efficacy is critical to the claimed invention. Further, applicant states that a prima facie case of obviousness based on routine optimization can be rebutted by a showing that a claimed parameter is disclosed in a very broad range in the prior art (remarks, pg 8).
Applicant is directed to MPEP 2144.05.III.D, which states, “One factor that may weigh against maintaining an obviousness rejection based on optimization of a variable disclosed in a range in the prior art is where an applicant establishes that the prior art disclosure of the variable is within a range that is so broad in light of the dissimilar characteristics of the members of the range as to not invite optimization by one of skill in the art. Genetics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc., 655 F.3d 1291, 1306, 99 USPQ2d 1713, 1725 (Fed. Cir. 2011)”. Thus, although a finding of a very broad range in the prior art may rebut a case of routine optimization, the dissimilar characteristics of the range need to be taken into consideration.
To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). (see MPEP 716.02(d).II). See also E.I. DuPont de Nemours & Company v. Synvina C.V., 904 F.3d 996, 1006, 128 USPQ2d 1193, 1201 (Fed. Cir. 2018.): "[A] modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art." (citing Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 693, 2023 USPQ2d 448 (Fed. Cir. 2023): "A difference of degree is not as persuasive as a difference in kind – i.e., if the range produces ‘a new property dissimilar to the known property,’ rather than producing a predictable result but to an unexpected extent." MPEP 2144.05.III.A. "Only if the `results of optimizing a variable' are `unexpectedly good' can a patent be obtained for the claimed critical range." (quoting In re Antonie, 559 F.2d 618, 620, 195 USPQ 6, 8 (CCPA 1977))); In re Wertheim, 541 F.2d 257, 267, 191 USPQ 90, 100 (CCPA 1976).
The doses within the antibody broad range of Kim are not dissimilar in kind and the results identified by applicant are not unexpectedly good; the examiner finds that the claimed dose was determined by routine methods using method known in the art.
Routine optimization is comprised of methods that are well-understood and conventional activities previously known to the industry. When considering whether the determination of the optimum or workable ranges of a variable (e.g., dose) might be characterized as routine experimentation, the particular parameter must first be recognized as a result-effective variable (see MPEP 2144.05(I)-(II). KSR International Co. v. Teleflex held that “obvious to try” was a valid rational for an obviousness finding when the invention is directed to a result-effective variable. In this case, an artisan prior to the effective filing date of the invention would have a reason to vary the dose of the anti-FcRn antibody of Kim, because Kim recognizes the dose as a result-effective variable and suggests the dose range 1 mg/kg to 2 g/kg and, more preferably, the dose range 1-40 mg/kg [0122]. When provided with all of the starting conditions, including the therapeutic of Kim and the target population of Kim and Blumberg, discovering the optimum or workable ranges for those components when performing the prior art method of treatment by routine experimentation does not make the instant claims patentable.
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).
Applicant asserts that fixed dosing is better for some monoclonal antibodies and body-size dosing is better for others (remarks, pg 7; Liang Declaration filed April 18, 2025). Furthermore, as Wang et al teaches that FcRn plays an important role in protecting IgG molecules from catabolism, changes in FcRn will likely affect the serum half-life of an antibody, supporting applicant’s argument of unpredictability when determining fixed or body-size dosing for the claimed antibody (remarks, pg 7). In view of applicant’s prior analysis of the Wang reference (pg 7) and the examiner’s failure to substantively address why one of ordinary skill in the art would have used fixed dosing for an anti-FcRn antibody, a modified rejection of the claims under 35 U.S.C. 103 over Kim in view of Wang et al, Fasanmade et al, and Blumberg is set forth above.
Given that administration of flat dose of therapeutic drug is more convenient and avoiding potential dose calculation mistakes, those skilled in the art would use the preferred dosage within the therapeutic window of 650-750 mg as taught by Kim as determined by the population PK optimization for the claimed anti-FcRn antibody using the program NONMEM taught by Fasanmade et al. That which is claimed is merely the optimization of variables within the claims that flow from the “normal desire of scientists or artisans to improve upon what is already generally known.” In re Peterson, 315 F.3d 1325, 1330 (Fed.Cir.2003).
With respect to applicant’s assertion that the examiner’s reliance on inherency in the prior office action is factually and legally flawed (remarks, pg 9-10), applicant’s arguments are persuasive and the inherency rationale is no longer relied upon for the obviousness rejection.
Conclusion
No claim is allowed.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675