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 .
DETAILED ACTION
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 23-25, and 28-29 have an effective filing date of 20JUN2024 corresponding to PRO 63/662,048.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/23/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restriction
In the response filed on 11/12/2025 Applicant elected without traverse:
Group I, claims 1-2, and 23-29
Status of Claims
Claims 23-25, and 28-29 are currently pending and presented for examination on the merits.
Claim 23 is amended.
Claims 1-22, 26-27, and 30 are canceled.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 112(a) is withdrawn in view of Applicant canceling the claims.
The rejections filed under 35 U.S.C. 112(b) are withdrawn in view of Applicant canceling the claims.
Rejections Maintained
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.
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 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 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Stals et al (WO 2024105445 A2, IDS 6/20/2025), and further in view of Freedholm et al (CA 3234626 A1).
In regards to claim 1, Stals et al teaches FcRn antagonist molecules [Abstract]. Stals et al further teaches an aqueous solution comprising an FcRn antagonist, rHuPH20, 20 mM L-histidine, 10 mM L-methionine, 0.04% (w/v) polysorbate 20, 100 mM sodium chloride, and about 60 mM sucrose, at a pH of 6.0 in an aqueous solution [0212-0213]. Stals et al further teaches the FcRn antagonist at 180 mg/ml [0213]. Stals et al teaches the FcRn antagonist is the therapeutic equivalent of efgartigimod [0222]. Stals et al further teaches using water [0210]. Stals et al further teaches using USP [0210].
With regard to concentration and amounts of components of the approved product, the amount of each component is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Stals et al does not specifically teach L-Histidine hydrochloride monohydrate. However, this deficiency is made up in the teachings of Freedholm et al.
Freedholm et al teaches an aqueous solution comprising L-Histidine hydrochloride monohydrate as a histidine buffer [0156].
One of ordinary skill, before the effective filing date, would have been motivated to combine Stals’s aqueous solution comprising an FcRn antagonist equivalent to efgartigimod, rHuPH20, L-Histidine, L-Methionine, polysorbate 20, sodium chloride, sucrose, USP, water, USP, at a pH of 6.0, with Freedholm’s aqueous solution comprising L-Histidine hydrochloride monohydrate as a histidine buffer. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Stals and Freedholm’s for an aqueous solution comprising efgartigimod, rHuPH20, L-Histidine, L-Histidine hydrochloride monohydrate, L-Methionine, polysorbate 20, sodium chloride, sucrose, USP, water, USP, at a pH of 6.0, because Stals and Freedholm both teach aqueous solutions for administration comprising the components of the instant claim.
In regards to claim 23, Stals et al teaches the FcRn antagonist is the therapeutic equivalent of efgartigimod [0222]. Stals et al further teaches administering with hyaluronidase [0212]. Stals et al further teaches treating generalized myasthenia gravis (gMG) [0220]. Stals et al further teaches treating antibody-mediated disorders [0219]. Stals et al further teaches FcRn antagonist are all capable of rapidly reducing the level of serum IgG antibodies [0007].
In regards to claim 24, Stals et al teaches FcRn antagonist molecules [Abstract]. Stals et al further teaches an aqueous solution comprising an FcRn antagonist, rHuPH20, 20 mM L-histidine, 10 mM L-methionine, 0.04% (w/v) polysorbate 20, 100 mM sodium chloride, and about 60 mM sucrose, at a pH of 6.0 in an aqueous solution [0212-0213]. Stals et al further teaches the FcRn antagonist at 180 mg/ml [0213]. Stals et al teaches the FcRn antagonist is the therapeutic equivalent of efgartigimod [0222]. Stals et al further teaches using water [0210]. Stals et al further teaches using USP [0210]. Stals et al further teaches a single-dose vial [0210]. Stals et al further teaches Stals et al teaches the FcRn antagonist is the therapeutic equivalent of efgartigimod [0222]. Stals et al further teaches administering with hyaluronidase [0212]. Stals et al further teaches treating generalized myasthenia gravis (gMG) [0220]. Stals et al further teaches treating antibody-mediated disorders [0219]. Stals et al further teaches FcRn antagonist are all capable of rapidly reducing the level of serum IgG antibodies [0007].
Claims 23-25, and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Stals et al (WO 2024105445 A2, IDS 6/20/2025), Freedholm et al (CA 3234626 A1), as applied to claims 1-2. and 23-24 above, and further in view of Argenx (argenx Presents Additional Efgartigimod Data from Global Phase 3 ADAPT Trial at the Myasthenia Gravis Foundation of America 2020 Scientific Session, Oct 2020) and Argenx 2021 (Label for HIGHLIGHTS OF PRESCRIBING INFORMATION, Argenx, 2021).
The teachings of Stals et al and Freedholm et al are discussed above.
Stals et al does not specifically teach response rates for the approved product. However, this deficiency is made up in the teachings of Argenx.
In regard to claims 25, Argenx teaches treating myasthenia gravis patient with efgartigimod [2nd Paragraph, pg. 1]. Argenx further teaches 67.7% efgartigimod-treated AChR-Ab+ patients were MG-ADL responders [Repeatability of response, pg. 2]. Argenx further teaches Quantitative Myasthenia Gravis (QMG) scores [Magnitude of response, pg. 2]. Argenx further teaches 63.1 % of AChR-Ab+ patients were responders to efgartigimod compared with 14.1 % on placebo on the QMG score [Key Topline Data, pg. 3]. Argenx further teaches 67.7% of efgartigimod-treated AChR-Ab+ gMG patients were responders on the MG-ADL score compared to 29.7% of placebo patients [Key Topline Data, pg. 3].
Stals et al does not specifically teach a label. However, this deficiency is made up in the teachings of Argenx 2021.
In regards to claim 28, Argenx 2021 teaches a label for efgartigimod use [Page 1].
In regards to claim 29, one of ordinary skill in the art would have found it obvious to counter any adverse reactions to the treatment to prevent injury to a patient. Furthermore, Argenx 2021 teaches drug warnings, precautions, adverse reactions, and drug interactions for efgartigimod [Page 1].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Stals’s aqueous solution comprising an FcRn antagonist equivalent to efgartigimod, rHuPH20, L-Histidine, L-Methionine, polysorbate 20, sodium chloride, sucrose, USP, water, USP, at a pH of 6.0, with Freedholm’s aqueous solution comprising L-Histidine hydrochloride monohydrate as a histidine buffer, with Argenx’s observed response rates, with Argenx 2021 label for use. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine the methods of Stals, Freedholm, Argenx, and Argenx 2021 for a product comprising a aqueous solution comprising efgartigimod, rHuPH20, L-Histidine, L-Histidine hydrochloride monohydrate, L-Methionine, polysorbate 20, sodium chloride, sucrose, USP, water, USP, at a pH of 6.0, because Argenx teaches the response rates of efgartigimod and Argenx 2021 teaches a label for efgartigimod and precautions for use.
Applicant’s Arguments:
As pointed out by the Examiner, Stals does not teach or suggest response rates for an approved product. Applicant submits that Freedholm fails to cure the deficiencies of Stals. Freedholm describes a single clinical study in mCRPC subjects using abiraterone acetate plus prednisone. There is no disclosure or suggestion in Freedholm of any approved drug product let alone the approved product of claims 23 and 24.
An approved product is the final result of a multi-year effort requiring deep innovation and the generation of substantial amounts of data from studies and experiments testing an investigational agent to assess whether that investigational agent(s) may be approved to treat or mitigate a disease. This is true for Vyvgart Hytrulo®. Its eventual FDA approval for treatment of gMG in June of 2023 was the result of years of effort, investment, and innovation. The data submitted to FDA proved that Vyvgart Hytrulo® was safe and effective for treating gMG under the conditions described in the product label (see Examples in the instant application). The path to FDA approval is unpredictable and difficult. Most investigational agents fail during trials (more than 89%) and the approval process is a long and complex path. The odds that an investigational molecule will progress to becoming an approved product are quite low as shown in the report published by the Biotechnology Innovation Organization (go.bio.org/rs/490-EHZ- 999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf). For autoimmune diseases the likelihood of approval is 10.7% as detailed in the BIO study and FIG. 5a from that report (FIG. 1 of the instant application).
Stals does not disclose or suggest an approved drug product according to claims 23-25 and 28-29. Stals fails to provide any suggestion or disclosure of any approved drug product, including any clinical study, any toxicology study, any adverse events, or any pK information. Nor does Stals suggest filing for an any regulatory approval to market an approved drug product- let alone the approved product of claims 23-25 and 28-29. Freedholm fails to cure the deficiencies of Stals for the reasons provided above.
Examiner’s Response:
In Applicant Arguments, dated 02/23/2026, Applicant asserts that “[a]n approved product is the final result of a multi-year effort requiring deep innovation and the generation of substantial amounts of data from studies and experiments testing an investigational agent to assess whether that investigational agent(s) may be approved to treat or mitigate a disease. This is true for Vyvgart Hytrulo®. Its eventual FDA approval for treatment of gMG in June of 2023 was the result of years of effort, investment, and innovation. The data submitted to FDA proved that Vyvgart Hytrulo® was safe and effective for treating gMG under the conditions described in the product label (see Examples in the instant application). The path to FDA approval is unpredictable and difficult. Most investigational agents fail during trials (more than 89%) and the approval process is a long and complex path. The odds that an investigational molecule will progress to becoming an approved product are quite low… For autoimmune diseases the likelihood of approval is 10.7%...”
These arguments have been fully considered but are not deemed persuasive. At [0004] - [0005], Stals et al teach that “[i]t is estimated that more than 2.5% of the human population is affected by autoantibody-driven autoimmune diseases, in which autoreactive antibodies are directly pathogenic. The half-life of IgG in the serum is prolonged relative to the serum half- life of other plasma proteins (Roopenian et al., J. Immunology 170:3528 (2003); Junghans and Anderson, Proc. Natl. Acad. Sci. USA 93:5512 (1996)). This long half-life is due, in part, to the binding of the Fc region of IgG to the Fc receptor, FcRn. Although FcRn was originally characterized as a neonatal transport receptor for maternal IgG, it also functions in adults to protect IgG from degradation. FcRn binds to pinocytosed IgG and protects the IgG from transport to degradative lysosomes by recycling it back to the extracellular compartment. This recycling is facilitated by the pH dependent binding of IgG to FcRn, where the IgG/FcRn interaction is stronger at acidic endosomal pH than at extracellular physiological pH… When the serum concentration of IgG reaches a level that exceeds available FcRn molecules, unbound IgG is not protected from degradative mechanisms and will consequently have a reduced serum half-life. Thus, inhibition of IgG binding to FcRn reduces the serum halflife of IgG by preventing IgG endosomal recycling of IgG. Accordingly, agents that antagonize the binding of IgG to FcRn may be useful for regulating, treating or preventing antibody-mediated disorders, such as autoimmune diseases, inflammatory diseases, etc (emphasis added).” At [00222] - [00233], Stals et al. teach that “[i]n some embodiments, clearance of total serum IgG is increased in a subject following administration of the FcRn antagonist molecule. In some embodiments, clearance of total serum IgG in a subject following a single therapeutic administration of the FcRn antagonist molecule is comparable to the clearance of total serum IgG in a subject following a single therapeutic administration of efgartigimod. In some embodiments, clearance of total serum IgG in a subject following a single therapeutic administration of the FcRn antagonist molecule is similar or the same as the clearance of total serum IgG in a subject following a single therapeutic administration of efgartigimod… In some embodiments, clearance of total serum IgG in a subject following a single administration of the FcRn antagonist molecule is comparable to the clearance of total serum IgG in a subject following a single administration of an equivalent amount of efgartigimod. In some embodiments, clearance of total serum IgG in a subject following a single administration of the FcRn antagonist molecule is similar or the same as the clearance of total serum IgG in a subject following a single administration of an equivalent amount of efgartigimod.” At [00220], Stals et al. teach that antibody-mediated disorders include autoimmune diseases, such as generalized myasthenia gravis (gMG).
Based upon these teachings, one of ordinary skill in the art would have been motivated to administer efgartigimod to gMG patients, because there would have been a reasonable expectation that such a method would lead to the clearance of total serum IgG, thus providing a therapeutic benefit to said gMG patients. It is further known in the art that gMG is associated with an increase of anti-acetylcholine receptor (AChR) antibodies. Additionally at [00212], Stals et al teach that “for SC [subcutaneous] administration, in certain embodiments, the FcRn antagonist molecules may be administered co-formulated with hyaluronidase, for example, in particular, rHuPH20. The co-formulated material will allow SC dosing of larger volumes.” Therefore the teachings of Stals et al. provided ample motivation for one of ordinary skill in the art to develop a method for treating gMG, comprising administering to a subject in need thereof a combination of efgartigimod and hyaluronidase, wherein said patients are anti-AChR antibody positive, as recited in claim 23.
Applicant’s arguments regarding FDA approval for treatment of gMG have been fully considered but are not deemed persuasive. The Office agrees that the path to FDA approval is difficult, with most drug candidates failing clinical trials; however as indicated above, the teachings of Stals et al. provided ample motivation for one of ordinary skill in the art to develop a method for treating gMG, comprising administering to a subject in need thereof a combination of efgartigimod and hyaluronidase, wherein said patients are anti-AChR antibody positive. Furthermore the FDA approval process and an obviousness analysis do not involve the same considerations. For example FDA approval is based upon drug safety and efficacy, while an obviousness analysis involves a determination of whether the prior art would motivate one of ordinary skill in the art to arrive at a particular invention. Although drug safety and efficacy may be evidentiary factors in an obviousness analysis, they are not the only factors, nor are they dispositive. Given the clear motivation for one of ordinary skill in the art to arrive at the claimed invention in light of the cited references, the weight of the evidence, when considered in its totality, supports the conclusion that the claim rejections under 35 U.S.C. 103 are valid and proper.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642