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 .
Claim Status
Claims 1, 3, 5, 9-12, 19, 21-22, 35, and 113 are pending; claims 18 and 20 were canceled; no claims were newly added; and claims 1, 19, and 113 were amended in the Reply field 4/30/2026. Claim 22 remains withdrawn. Claims 1, 3, 5, 9-12, 19, 21, 35, and 113 are presently considered.
Election/Restriction
Applicant’s election without traverse of Group I and the species of Example 1 consisting of a single emulsion formulation of zilucoplan (SEQ ID NO: 1) in combination with RESOMER®502H (acid terminated 7-17k MW) with 37% loading as described at ¶¶[0269]-[0272] of the Specification filed 10/21/2021 in the reply filed on 9/23/2024 has been acknowledged.
The elected species is understood as follows: The originally elected species is a single emulsion formulation of Zilucoplan in the form of a microsphere particle, wherein the “release modulating matrix” is the PLGA of RESOMER®502H (acid terminated 7-17k MW), and the elected species is understood to consist of a polymer of poly(D,L-lactide-co-glycolide) in a 50:50 ratio. The “zilucoplan-PLGA particles” of unspecified diameter and are not spherical (see, e.g., Spec. filed 10/21/2021 at ¶¶[0271], noting that the particles had a “collapsed or concave sphere structure”, rather than spherical, but no diameter was actually identified for the 37% loaded formulation). “37% loading” is presumed to mean percent w/w between SEQ ID NO: 1 (or PLGA) over the total (e.g., SEQ ID NO: 1 and PLGA). Zilucoplan is understood to correspond to the sodium salt structure of
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631
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(see, e.g., Spec. filed 10/21/2021 at ¶¶[0031], [0270]), which comprises instant SEQ ID NO: 1, and is the prior art element1 of Zilucoplan.
The amended claims are understood to continue reading upon the originally filed disclosure, and the original search has been repeated. Following extensive search and examination, the originally elected species has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 1, 3, 5, 9-12, 19, 21, 35, and 113 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claim 22 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/21/2024.
Claims 1, 3, 5, 9-12, 19, 21, 35, and 113 are presently considered.
Priority
The priority claim to Pro 62/837,978 (filed 4/24/2019) is acknowledged.
Information Disclosure Statement
The IDS filed on 4/30/2026 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action (see, e.g., MPEP § 2111.01(IV)).
Claim 1 is representative of the pending claim scope. Applicable claim interpretations are set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
Regarding the preamble reciting “a sustained release formulation”, per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claim 1 is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of claim 1 (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”).
Amended claim 1 now recites the phrase “a single emulsion of condensed particles in an aqueous continuous phase”. This phrase is not clearly defined on record or in the prior art. It first appeared in the amendments filed 9/30/2025. For purposes of examination, this phrase has been understood to require particles (i.e., a discrete phase) to be suspended within water (i.e., an aqueous continuous phase). In view of the originally elected species, the phrase was previously understood to correspond to a single oil-in-water emulsion (see, e.g., Spec. filed 10/21/2021 at ¶[0271]), and therefore this limitation was understood to require that the particles are suspended in an aqueous solution (see, e.g., Action mailed 1/15/2026 at 5-6). Critically, Applicant has not disputed this interpretation with specificity (see, e.g., Reply filed 4/30/2026, passim).
References to “a sustained release formulation” are understood to refer to the claimed invention as a whole, whereas references to “a release modulating matrix” are understood to specifically refer only to that specific subcomponent of the claimed invention. In the originally elected species, the “release modulating matrix” is the PLGA polymer is RESOMER®502H (acid terminated 7-17k MW).
Instant SEQ ID NO: 1 and the description at previously pending claims 13-17 (canceled in Reply filed 3/06/2025) are understood to be fully satisfied by Zilucoplan. “Zilucoplan” has a PubChem CID of 133083018 and corresponds to a CAS No. of 1841136-73-9, and is also referred to RA101495, among other names. The structure of Zilucoplan associated with RA101495 and CAS No. 1841136-73-9 was disclosed in the prior art at least by 5/16/20182. Accordingly, all names associated the prior art structure, including Zilucoplan, RA101495, CAS No. 1841136-73-9, etc. would have been known, searchable, and recognized by artisans as synonyms prior to the instantly filed application.
Claims 1, 5, 12, and 19 recite the term “about”, which is not defined on record. Accordingly, the term “about” is given its ordinary meaning in view of the biochemical arts, and is understood to mean “within 20 percent” (see, e.g., US 2009/0028832 A1 at ¶[0111]; see also US 2009/0105341 A1 at ¶[0049]; see also US 2012/0178676, at ¶[0277]). Accordingly, with respect to the instant disclosure and with prior art of record, unless the term “about” is otherwise clearly defined, the term is reasonably inferred to indicate a range “within 20 percent” of a recited number. For example, the range of “about 50:50” is reasonably inferred to include at least a range of 40:60 to 60:40.
In the Reply filed 4/30/2026, claim 1 was amended to recite “wherein the sustained release formulation comprises from about 36% to about 38% of Zilucoplan by percent weight”. Critically, this newly added phrase “wherein the sustained release formulation comprises from about 36% to about 38% of Zilucoplan by percent weight” recites a hoped-for and desired result or outcome, but it does not recite any specific, required structures necessary or sufficient to actually achieve this result other than those explicitly enumerated at claim 1 (i.e., the known drug of “zilucoplan” combined with the known drug carrier of PLGA, combined in a known and routine manner in the art, namely a single oil-in-water emulsion). Furthermore, because this “wherein” clause does not correspond to any known structure/function relationship of record, then claim 1 is presumed fully enabled under 35 USC §112(a) for the entire scope of instant claim 1. This is pertinent because claim 1 broadly includes any salt of Zilucoplan combined with any forms of PLGA (e.g., acid-terminated and non-acid terminated PLGAs, PLGAs of any molecular weight). Critically, claim 1 does not recite nor require any excipient or emulsion stabilizers to be present, or for any narrower range of “poly lactic and poly glycolic acid” than “about 25:75 to about 75:25” (see claim 1). Presently, the full scope of claim 1 is presumed fully enabled under 35 USC 112(a); therefore, in the absence of evidence to the contrary, the “wherein” clause at amended claim 1 is understood to be satisfiable by any single oil-in-water emulsion of any PLGA with any form of Zilucoplan, without additional additives or excipients.
Additional claim interpretations are set forth below.
Withdrawn Rejections as Necessitated by Applicant Amendment
The rejection of claims 1, 3, 5, 9, and 12 under 35 U.S.C. 103 as being unpatentable over WO2015/191951A23 (Dec. 17, 2015) and further in view of Mader4, is withdrawn in view of the amendments to claim 1 as filed 4/30/2026. However, the rejection has necessitated a revised rejection, which is set forth below.
The rejection of claims 1, 3, 5, 9-12, 18-21, 35, and 113 under 35 U.S.C. 103 as being unpatentable over WO2015/191951A2 in view of Mader5 as applied to claims 1, 3, 5, 9, and 12 above, and further in view of Han6 and Acharya7, is withdrawn in view of the amendments to claims 1, 19, and 113; cancellation of claims 18 and 20; and in view of the withdrawal of the base rejection of WO’951 in view of Mader. However, the amendments have necessitated a revised rejection, which is set forth below.
Revised Rejections as Necessitated by Applicant Amendment
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, 3, 5, 9-12, 19, 21, 35, and 113 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015/191951A2 in view of Mader8, Han9 and Acharya10.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claim 1, and the structure Zilucoplan (i.e., a lipidated polypeptide of instant SEQ ID NO: 1), WO’951 discloses C5 inhibitors (see, e.g., WO’951 at ¶[00171]), including instant SEQ ID NO: 1 (see, e.g., WO’941 at Tables on 60 and 100, disclosing SEQ ID NO: 194 as “R3193”, having the structure [cyclo(l,6)] Ac-K-V-E-R-F-D-(N-Me)D-Tbg-Y-azaTrp-E-Y-P-Chg-B2811,12; see also id. at ¶[00268], reducing to practice R3193 with a lipophilic moiety conjugated to the lysine residue; see also id. at Substance Table on 156 at Substance 194, identifying it as CAS NO. 1841136-73-9). R3193 was one of only two lipidated polypeptides (see, e.g., WO’941 at ¶[00268]), and WO’941 identifies that such “Lipidation resulted in an increase in . . . [AUC] by 2.1-fold” to “2.7-fold”, depending upon administration route (see, e.g., WO’941 at ¶[00300]), and therefore Zilucoplan is a prior art element having a known utility (i.e., C5 inhibitor), and it would be reasonably expected to exhibit a 2.1-2.7-fold increase in AUC relative to non-lipidated compounds. Regarding claim 9 and the presence of an excipient, WO’951 explicitly claims formulations comprising excipients (see, e.g., WO’951 at ¶¶[0017], [00156], claims 1, 17, 20-21, 26).
The prior art of WO’951 differs from the instantly claimed invention as follows: WO’951 does not explicitly reduce to practice R3193 (i.e., Zilucoplan) in an oil-in-water emulsion with a PLGA polymer comprising a ratio of poly lactic acid to poly glycolic acid of from about 25:75 to about 75:25, and about 36% to about 38% of zilucoplan by percent weight, as required by amended claim 1.
WO’951 directs artisans to formulate R3193 (i.e., Zilucoplan) in emulsions. Regarding instant claims 1, 3, 5, 9, 12, and emulsions: WO’951 identifies that R3193 (i.e., Zilucoplan) could be formulated in emulsions, microemulsions, and time release formulations (see, e.g., WO’951 at ¶¶[00153]-[00154], [00157], [00236]).
WO’951 discloses that PLGA was a known element suitable for use in formulations comprising R3193 (i.e., Zilucoplan): Regarding instant claims 1, 3, 5, 9, 12, and emulsions: WO’951 identifies that R3193 (i.e., Zilucoplan) could be formulated in emulsions (see, e.g., WO’951 at ¶¶[00153]-[00154], [00157], [00236]), and formulated with the carriers of Poly(L-lactide-co-glycolide) copolymer (i.e., PLGA) (see, e.g., WO’951 at ¶[00157]).
The disclosure of WO’951 that R3193 (i.e., Zilucoplan) could be formulated in emulsions and with PLGA would lead artisans to review commercially available PLGA and emulsion-related information: Regarding instant claims 1, 2, 5, 12, 35, and PLGA, Mader discloses that the PLGA of RESOMER®502H (50:50 PLGA) was commercially available and sold for the purpose of being utilized in a drug delivery system (see, e.g., Mader at title on 62, 62 at Table 1, 62 at Fig. 2, 63 at col I-II at § Implant Formulation, 63 at Fig. 3, 65 at Table of “RESOMER® Products”). Regarding instant claim 1, claim 5, and a ratio of 50:50 lactide/glycolide in the PLGA, Mader identifies that RESOMER®502H was commercially available as an acid-terminated, 50:50 PLGA, having a Mw of 7-17k (see, e.g., Mader at 65 at Table of “RESOMER® Products”). Regarding claims 1, 3, 12, and microparticles with a diameter range of “about 5 µm to about 200 µm”, Mader identifies that PLGA RESOMER® Products could be utilized to make microparticles with diameters ranging from at least 200 nm to 50 µm (see, e.g., Mader at 63 at col I-II at § Implant Formulation, 63 at Fig. 3).
Single “oil-in-water”13 emulsions were well-known in the prior art and commonly utilized to formulate drug delivery microparticles: Regarding amended claims 1, 3, 5, 9-12, and the particles formed by “single emulsion of condensed particles in an aqueous continuous phase” 14, WO’951 identifies that R3193 (i.e., Zilucoplan) could be formulated in emulsions (see, e.g., WO’951 at ¶¶[00153]-[00154], [00157], [00236]), which would necessarily include emulsion methods already known in the prior art (see also Mader at 63 at col II at 1st partial, identifying that PLGA may be utilized to “deliver therapeutic agents via microparticle encapsulation”, wherein “loaded microparticles are commonly prepared via . . . emulsification”). Han and Acharya are cited herein to establish that single “oil-in-water” emulsion methods were well-known in the prior art using PLGA-based polymers (see, e.g., Han at title, abs, Table 1 on 3-4, Table 2 at p. 6, showing oil-in-water single emulsion in aqueous phase; see also Acharya at title, abs).
Methods of formulating and optimizing single “oil-in-water” emulsions to contain a wide range of drug loading were known in the prior art: Regarding amended claims 1, 3, 5, 9-12, 19, 35, 113, and single “oil-in-water” emulsions comprising “from about 36% to about 38% of zilucoplan by percent weight”, per MPEP § 2144.05(I), in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Here, Han identifies that PLGA delivery systems may have different particle sizes, different drug loading percentages, different drug release profiles, and may be utilized to encapsulate a wide-range of drugs (see, e.g., Han at title, abs, Table 1 on 3-4; see also Han at Table 1(4) on p. 4, p. 5 at col II at § Hydrogel Templates, reasonably informing artisans that single-emulsion methods could be improved in different ways, including additives, hydrogel templates, etc.). Accordingly an artisan would readily appreciate that such PLGA emulsification has multiple parameters that may be optimized by routine optimization methods. Furthermore, the range of “from about 36% to about 38% of zilucoplan by percent weight” at amended claim 1 is not a product-by-process limitation or a functional limitation requiring specific structures to achieve the outcome claimed. Therefore, the relevant issue is whether or not such ranges were already known in the single “oil-in-water” emulsion arts. Critically, Han identifies that drug loading varies depending upon drug used, particle size, and method of particle manufacture, and that drug loading was already known to vary from at least 1% drug loading to >57% (w/w) drug loading (see, e.g., Han at Table 1(1) and Table 1(3) on p. 3, Table 1(3) and Table 1(4) on p. 4, p. 5 at col II at § Hydrogel Templates, Table 2 at p. 6-7; note that the PLGA content is understood to be the 100% - drug loading percentage (w/w); see also Acharya at title, abs, identifying a method for making microparticles of 200 nm to >50µm, having a drug loading capacity of 50% or higher with minimal initial burst release). Accordingly, the prior art teaches that, circa 2016, artisans knew how to obtain drug loading percentages (w/w) within the ranges of at least 1-57% (see id.; see also Acharya at abs, disclosing drug loading capacity of 50% or higher), which overlaps in scope with the claimed ranges (see, e.g., MPEP § 2144.05(I), "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Furthermore and in addition to the obviousness of overlapping ranges in view of MPEP § 2144.05(I), such ranges are not patentably distinct in view of the prior art per MPEP § 2144.05(II), per MPEP § 2144.05(II),
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)
Here, no criticality of range commensurate in scope with the pending claim scope and commensurate in scope with the requirements of MPEP § 716.02 have been placed on record. Rather, per MPEP § 2144.05(II), it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable because "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation" and "No invention is involved in discovering optimum ranges of a process by routine experimentation" since the "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art" (see, e.g., MPEP § 2144.05(II)). Here, Han identifies that PLGA delivery systems may have different particle sizes, different drug loading percentages, different drug release profiles, and may be utilized to encapsulate a wide-range of drugs (see, e.g., Han at title, abs, Table 1 on 3-4), and Han identifies that known means of improving emulsion methods were known in the prior art (see, e.g., Han at Table 1(4) on p. 4, p. 5 at col II at § Hydrogel Templates). Furthermore, Mader identifies that it was well-understood that RESOMER® PLGA polymer selection impacted drug delivery (see, e.g., Mader at 62 at Table 1 and Fig. 2). Mader identifies that
The release profile depends on the size distribution and porosity of the microparticles, the drug characteristics and concentration, and the release conditions. . . . The release profile can be adjusted by appropriate formulation parameters. For example, linear release, pulsed release (e.g., for vaccination with no burst release, and a tunable lag phase release can be achieved”
(see, e.g., Mader at 63 at col II at 1st ¶).
Mader further identifies that, for PLGA, “degradation takes place for approximately three weeks” (see, e.g., Mader at 63 at col II at 4th ¶, Fig. 4), and that the release of peptides “can be [] over days to several weeks” (see, e.g., Mader at 64 at col I at 2nd ¶). In addition, Han exemplifies that microparticle drug delivery systems have wide ranges of achievable and obtainable drug release profiles, which can vary from sustained release over a 550 hr period or 90% release in over 21 days, to no initial burst and sustained release for over 3 months (see, e.g., Han at Table 1(1) and 1(3) on 3, Table 1(4) on 4). Like Mader, Han also identifies that
…the desired release rates can be achieved by adjusting the ratio of lactic acid to glycolic acid and by altering the physiochemical properties [e.g., Mr, end-group (ester or carboxylic) functionality] that influence microparticle morphology.
(see, e.g., Han at Table 1(1) and 1(3) on 3, Table 1(4) on 4).
Accordingly, one of ordinary skill in the art would readily appreciate that the art-recognized and achievable drug loading and release profiles were generally known in the prior art, overlapped with the claimed ranges (see also MPEP § 2144.05(I)); and that a desired drug loading, particle size, and release provide could be achieved via routine optimization of art-recognized variables and formulation parameters as taught by Mader and Han (e.g., size distribution, porosity, drug concentration, ratio of lactic acid to glycolic acid, Mr, end-group chemistry, etc.). Accordingly, an artisan would readily appreciate that PLGA emulsification methods were well-known in the art, and were routinely optimized for specific drugs and intended applications. Since Applicant has not disclosed that the specific limitations recited in instant claims 1, 19, and 113 are for any particular purpose or solve any stated problem and the prior art teaches that microparticle drug loading and drug release profiles often vary according to the intended application and drug being utilized, and drug loading profiles could vary from at least 1-57%, and various parameters appear to work equally as well, absent unexpected results commensurate in scope with the instant claims, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the PLGA microparticle drug delivery arts.
Regarding claim 12 and particle size, Han identifies that microparticles have “optimal release profiles” with diameters within the range of “10-200 µm” (see Han at p. 2 at col II at § Particle Size; see also Acharya at abs; see also MPEP § 2144.05(I)).
Regarding amended claims 9-11 and 35 and the emulsion stabilizer of polyvinyl alcohol (PVA), Han identifies that PVA is the “most widely used emulsifier in the preparation of PLGA micro/nanoparticles” (see, e.g., Han at 5 at col I at § Choice of Surfactant).
Regarding instant claim 35 and product-by-process language utilizing PVA, instant claim 35 is directed to a product, but recites limitations directed to a product-by-process (see instant claim 35). Per MPEP § 2113(I),
[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
Accordingly, claim 35 is rejected as obvious for the reasons applied to claims 1, 5, and 9, as set forth above (see also Han at 5 at col I at § Choice of Surfactant, noting that PVA is the “most widely used emulsifier in the preparation of PLGA micro/nanoparticles” and is used to “ensure droplet stability”).
Regarding claim 21 and uniform distribution, Han identifies multiple methods for making PLGA-based microparticles for use in drug delivery (see Han at Table 2 on 6-7); and Han identifies hydrogel templates that are reasonable understood to have a uniform distribution of drug within the matrix (see id at 7). Similarly, Acharya identifies that such hydrogel templates yields homogenous size distributions (see, e.g., Acharya at abs), and that such microparticles are made by pouring a “solution or a paste of drug/polymer mixture” into a “gelatin mold” (see, e.g., Acharya at 315 at Fig. 1, 315 at col I at 1st full ¶), which is reasonably inferred to yield a uniformly distributed drug within PLGA (see, e.g., Acharya at Fig. 3 on 316, noting uniformly distributed dye). Furthermore, such structures are identified as “homogenous” (see, e.g., Acharya at Fig. 2 on 316), and are therefore understood to be uniform. Accordingly, uniform distribution as claimed is understood to be an obvious result of prior art methods of forming microparticles.
Predicted and Expected Results
The combination of a prior art drug (Zilucoplan) and a known PLGA 50:50 polymer of RESOMER®502H would yield predictably and expected results: R3193 is identified as a C5 inhibitor of the invention (see, e.g., WO’951 at ¶[00171]), wherein such polypeptides have known applications in the treatment of disorders, conditions, and diseases (see, e.g., WO’951 at ¶[00194]), including the treatment of paroxysmal nocturnal hemoglobinuria (PNH) as well as autoimmune diseases and disorders, neurological diseases and disorders, blood diseases and disorders, and infectious diseases and disorders (see, e.g., WO’951 at ¶¶[00194]-[00195]). In combination with PLGA RESOMER®502H, the drug formulation would be predicted and expected to have such disclosed utility in addition to the benefits attributable to the drug delivery systems (see, e.g., Mader at title on 62, 62 at Table 1, 62 at Fig. 2, 63 at col I-II at § Implant Formulation, 63 at Fig. 3). Furthermore, as noted above, WO’951 literally directs artisans to utilize PLGA polymers with the disclosed inhibitors in formulations such as emulsions, microemulsions, and time release formulations, etc. (see, e.g., WO’951 at ¶¶[00153]-[00154], [00157], [00236]).
Conclusion
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the combination of prior art elements (i.e., a known drug, a commercially available PLGA drug carrier, and a known emulsion stabilizer of PVA) according to known prior art methods of forming PLGA emulsions using routine methodologies in the PLGA emulsion arts, wherein such combination merely produces the predicted and expected results taught and disclosed by the prior art, namely a known drug with a known drug-carrier formulated as an emulsion suitable for use in pharmaceutical applications taught by the primary reference, wherein the emulsion-specific limitations are within the known ranges taught and disclosed for use with emulsions by Mader, Han, and Acharya (see, e.g., MPEP §§ 2143(I)(A), (G), MPEP § 2144.05(I)). In addition or alternatively, RESOMER®502H was a commercially available therapeutic drug delivery system, explicitly mentioned in the primary reference, and well known in the drug delivery arts as established by Mader, Han and Acharya, wherein the invention is understood to be the simple selection of known materials (e.g., PLGA delivery systems, formulated as an emulsion as known in the PLGA arts as an emulsion, loaded within range taught by PLGA arts, diameter as taught in the PLGA arts) based on the PLGA delivery system’s suitability for its intended purpose of forming a microparticle drug delivery system is obvious because the claims are directed to a combination of prior art elements that merely perform their same art-recognized, expected, and predicted functions when in combination as they do separately (see, e.g., MPEP § 2143(I)(A), MPEP § 2144.0715,16).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine a known prior art therapeutic compound with a known and commercially available prior art drug carrier, formulated according to known methods of emulsifying therapeutics, to arrive at a pharmaceutical formulation suitable for treating the same, exact conditions and patient populations taught and disclosed by the prior art.
Accordingly, claims 1, 3, 5, 9-12, 19, 21, 35, and 113 are are rejected.
Response to Arguments
Applicant's arguments filed 4/30/2026 have been fully considered but they are not persuasive for the reasons set forth below. Examiner notes that some arguments are rendered moot in view of the revised rejection as necessitated by Applicant’s amendments. Remaining applicable arguments are addressed below.
Summary of Examiner’s position: The Examiner’s position is that the therapeutic drug was known in the prior art and that PLGA emulsions were a well-known and conventional means of drug delivery at the time of filing. Therefore, the invention is the combination of known elements according to known methods to achieve predicted and expected outcomes. This is sufficient to sustain a determination of obviousness per KSR:
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007).
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Here, zero evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716.01 and 716.02 have been placed on record; accordingly, the prior art elements could have been combined by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. Accordingly, the rejections are maintained as revised above.
Allegation that Han “teaches away” from the claimed invention: It is the Examiner’s understanding that Applicant is suggesting that Han “teach away” from the claimed invention (see, e.g., Reply filed 4/30/2026 at 8 at 1st full ¶ to page 9 at 3rd full ¶). It is the Examiner’s understanding that Applicant provides the conclusory statement that “Han nevertheless teaches that single emulsion methods are not suitable for producing PLGA-based particles with high drug loading for sustained release formulations” (see, e.g., Reply filed 4/30/2026 at 9 at 2nd ¶), “use of hydrogel templates… none of which are single emulsion methods” (see, e.g., Reply filed 4/30/2026 at 9 at 1st ¶), and “Han teaches away from using such single emulsion formulations as having particular disadvantages” (see, e.g., Reply filed 4/30/2026 at 9 at 3rd ¶). These conclusory statements are based presumably upon the disclosures at the abstract and Table 2 of Han (see, e.g., Reply filed 4/30/2026 at 8 at 1st full ¶ to page 9 at 3rd full ¶). This position is not credible as follows: Applicant misrepresents the Han disclose, which broadly explains that
Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens….The obstacles hindering more wide spread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges.
(see, e.g., Han at abs, emphasis added).
Accordingly, Han does not “teach away” from single emulsions, but instead discusses known strategies at addressing common challenges related to PLGA formulations. For example, Han directs artisans to improve such formulations (including single-emulsion formulations) by
altering the form of the therapeutic molecule (see, e.g., Han at 2 at col I-II at §§ Physicochemical Properties of the Incorporated Drug(s), Table 1 at 3-4);
optimizing particle size (see, e.g., Han at 2 at col II at §§ Particle Size, Table 1 at 3-4);
utilizing additives complexed with PLGA (see, e.g., Han at 8 at col II at § “Complexing PLGA with Additives”, Table 1 at 3-4);
altering the chemistry of the PLGA (e.g., Mr, end-group functionality) (see, e.g., Han at 4 at col I at § Physicochemical Properties of the Biopolymer); and
choice of surfactant, such as a stabilizing emulsifier (e.g., PVA or poly(vinyl alcohol)) (see, e.g., Han at 4 at col I at § Choice of Surfactant).
All of these improvements are applicable to single or double emulsions, and would be expected to improve upon existing prior art methods by increasing drug-loading. In addition, Applicant explicitly cites the abstract of Han as identifying that “low drug loading, particularly of hydrophilic small molecules….” (see, e.g., Reply filed 4/30/2026 at 8 at 3rd full ¶, emphasis in original). Applicant’s reliance upon this statement is contradicted by their own subsequent admission that clearly identify that Zilucoplan is not a “small molecule” (see, e.g., Reply filed 4/30/2026 at 10 at 1st full ¶), and therefore the relevance of such statements in support of a “teaching away” is unknown and not established on record. Finally, the Applicant’s assertion that hydrogel-template methods are not a “single emulsion method” is not scientifically accurate17 and is unsupported by any objective evidence of record (see, e.g., Reply filed 4/30/2026 at 9 at 1st ¶). In sum, Han does not “teach away” from the claimed invention because the disclosure does not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)), but instead Han provides multiple methods applicable to single and double emulsion approaches that would be predicted and expected to improve drug loading. Accordingly, no “teaching away” has been identified on record.
Allegation that Acharya “teaches away” from the claimed invention or is otherwise non-analogous art: It is the Examiner’s understanding that Applicant is suggesting that Acharya “teach away” from the claimed invention (see, e.g., Reply filed 4/30/2026 at 9-10 at bridging ¶), and that “like Han, Acharya teaches that single emulsion methods are not suitable for producing PLGA-based particles with high drug loading for sustained release formulations” (see, e.g., Reply filed 4/30/2026 at 9-10 at bridging ¶), and “Acharya leads one of ordinary skill in the art to the use of hydrogel template methods rather than single emulsion methods” (see id). This position is not convincing or credible because:
First, Applicant’s conclusory assertions are not supported by Acharya because Acharya does not use the terms “single emulsion” or “double emulsion”, and therefore it is prima facie unclear upon what objective evidence Applicant is basing their conclusions (see, e.g., Acharya at title, abs, passim).
Second, Applicant provides zero evidence that Acharya and hydrogel template methods do not pertain to “single emulsions” as presently claimed. To the contrary, hydrogel template methods as disclosed by Acharya would be readily understood by artisans to include single-emulsions (see, e.g., US20170333304A1 at ¶¶[0034], [0131], referring to “the water/oil ratio when the hydrogel particles are made with a single-emulsion technique” and “hydrogel particles fabricated by single-emulsion technique”).
Third, furthermore, although Acharya does not recite “single” or “double” emulsion, Acharya explicitly pertains to “homogeneous nano/microparticles”, which are understood to be “homogeneous” and therefore be monolithic (solid in water) structures (see, e.g., Acharya at title, abs, passim, Fig. 1 on 315, 316 at col I at 2nd full ¶ referring to “Free and homogeneous polymer particles”). Accordingly, the usage of “homogeneous” in the context of Acharya and PLGA microparticles suggest a monolithic (solid solution matrix) formed via a single emulsion.
Accordingly, Acharya does not “teach away” from the claimed invention because the disclosure does not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Furthermore, in response to applicant's argument that Acharya is nonanalogous art limited to double emulsions, this argument has been deemed not credible and contradicted by the evidence of record, and therefore not persuasive.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding achieving a drug loading of “about 36% to about 38% by weight”: It is the Examiner’s understanding that Applicant is alleging that the prior art is not fully enabled or operable to achieve a drug loading amount of Zilucoplan within a single emulsion at “about 36% to about 38% by weight”, because although the prior art does in fact teach that drug loading can range from at least 1-57% (w/w), the teachings of the prior art are allegedly “nearly exclusively directed to small molecules . .. or proteins” and therefore allegedly
do not translate into similarly achievable loadings for polypeptide drugs. let alone macrocyclic polypeptide drugs, in a sustained release formulation comprising a single emulsion of condensed particles in an aqueous continuous phase. That is, contrary to the Office's assertion, the disclosure of Han does not reasonably suggest to one having ordinary skill in the art that the same or substantially similar high drug loadings can be achieved for macrocyclic polypeptide drugs (e.g., zilucoplan) as for small molecule drugs.
(see, e.g., Reply filed 4/30/2026 at 10-11 at bridging ¶, emphasis in original)
Applicant further alleges that the disclosure of Acharya would similarly be dismissed, ignored, or otherwise deemed not enabling because it only exemplifies a small molecule drug (see, e.g., Reply filed 4/30/2026 at 11 at 1st full ¶ to 11-12 at bridging ¶; see also id. at 12 at § 2 to page 14 at 1st partial ¶). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Notably, in direct contrast to Applicant’s position, neither Han nor Acharya exclude proteins or peptide “drugs”, but rather are understood to generally encompass all “drugs” including polypeptide therapeutics. Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 4/30/2026 at 10-11 at bridging ¶, 11 at 1st full ¶ to 11-12 at bridging ¶, 12 at § 2 to page 14 at 1st partial ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), which includes all types of therapeutic drugs. As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 4/30/2026 at 10-11 at bridging ¶, 11 at 1st full ¶ to 11-12 at bridging ¶, 12 at § 2 to page 14 at 1st partial ¶). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Allegation that Acharya “teaches away” from the claimed invention: It is the Examiner’s understanding that Applicant is suggesting that Acharya “teaches away” from the claimed invention, and specifically that “Acharya itself suggests that its as-disclosed particles prepared by a hydrogel template method are not suitable for polypeptide drugs” based upon a quote taken out of context (see, e.g., Reply filed 4/30/2026 at 11 at 1st full ¶, citing to Acharya at 318 at col. I). This is not persuasive because Acharya merely states that the disclosed teachings could be extended “to generate a comprehensive library of microstructures….such multi-layered structures are useful in making even more advanced structures, e.g., capsules”, wherein such capsules could be utilized with “fragile drugs, such as peptide and protein drugs, and in making multi-functional systems” (see Acharya at 318 at col I-II at bridging ¶). This disclosure does not state that peptide and protein drugs are not usable with the disclosed hydrogel templates; rather, in direct contrast to the Applicant’s interpretation, Acharya states
The ease and flexibility of the hydrogel template approach are expected to find applications in delivery of diverse drugs, ranging from low molecular weight hydrophobic drugs to high molecular weight proteins…..
A hydrogel template approach was developed to prepare homogeneous nano/micro structures of various geometries. This can be readily applicable for the large scale production of nano/microparticles because of its easiness in producing particles. The flexibility in forming different microstructures allows the approach to incorporate diverse drugs with various hydrophilic characters and molecular weights. The study demonstrated production of particles in various geometries and sizes with high precision. Drug loading is also shown to be very high with controllable drug release kinetics. The hydrogel template approach provides a new avenue of preparing nano/microparticles for drug delivery
(see Acharya at 318 at col I-II).
Accordingly, stating that a particular “capsule” structure could be utilized with peptides and proteins is not synonymous or equivalent to the statement that peptides and proteins can only be utilized in a “capsule” structure. Accordingly, Applicant’s position is not supported by the cited portion of Acharya, and is contradicted by the disclosure when considered in proper context as shown above. In sum, Acharya does not “teach away” from the claimed invention because the disclosure does not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)).
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of successfully achieving a drug loading value within the range of 1-57% (w/w) because the loading ranges in the prior art were not limited to polypeptides but rather applied to “drugs” generically (see, e.g., Reply filed 4/30/2026 at 11 at final ¶ to 12 at 1st partial ¶, alleging that the Office erroneously extrapolated drug loading values “for small molecule drug loaded-microparticles as valid for polypeptide drug-containing particles”; see also id. at 12 at § 2 to page 14 at 1st partial ¶). This is not persuasive. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior arts teachings pertaining to drug loading generically, is generically applicable to drugs, without exception, and that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), which includes all types of therapeutic drugs. As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive. Accordingly, Applicant’s position is not persuasive because Applicant has provided no rationale explaining why disclosures pertaining generically to therapeutic drugs would be reasonably interpreted to exclude entire categories of art-recognized drugs. Such arguments are unsupported by objective evidence and appear conclusory in nature.
Unexpected Results
Allegations of unexpected results: It is the Examiner’s understanding that Applicant is alleging the existence of unexpected results based upon Example 1 and 2 of record (see, e.g., Reply filed 4/30/2026 at 14 at § 3 to page 20 at final ¶). The Examples of record were previously fully considered but not found sufficient to establish unexpected results for reasons of record (see, e.g., Action mailed 1/15/2026 at 22-24), at least because such data is not (i) statistically significance as required by MPEP § 716.02(b); (ii) is not commensurate in scope with the claimed instant invention (see, e.g., MPEP § 716.02(d)); (iii) zero evidence criticality of range has been placed on record commensurate in scope with MPEP §§ 716.02(a), (b), and (d) both inside and outside the range claimed; and (iv) obtaining drug loading of PLGA single-emulsion particles between 1-57% is the expected and predicted result (see, e.g., MPEP § 716.02(c)(II)). The discussion of record is incorporated into the instant action.
Allegations that Examples 1 and 2 satisfy the requirements of MPEP § 716.02(b): It is the Examiner’s understanding that Applicant again alleges the existence of unexpected results based upon Example 1 and 2 of record (see, e.g., Reply filed 4/30/2026 at 14 at § 3 to page 20 at final ¶), acknowledges the Examiner’s response of record (see, e.g., Reply filed 4/30/2026 at 15 at 1st ¶ to page 20 at final ¶), and disputes the Examiner’s position that the proffered data lacks statistical significance (see, e.g., Reply filed 4/30/2026 at 16 at 2nd full ¶ after bullets, 17 at penultimate ¶). Statistical significance requires an identification of a test for statistical significance, and then an analysis using that test, wherein the result supports a conclusion of mathematical significance. Here, Applicant fails to identify that any statistical test was conducted and fails to provide any data evidencing that the proffered data is statistically significant. Statistical significance is not subject to opinion, but is shown objectively and mathematically. In the absence of such data, the proffered data continues to fail to satisfy MPEP § 716.02(b). On this basis alone, no unexpected results commensurate in scope with the requirements of MPEP § 716.02 and sufficient to rebut prima facie obviousness have been established on record.
Allegations that Examples 1 and 2 satisfy the requirements of MPEP § 716.02(d): It is the Examiner’s understanding that Applicant again alleges the existence of unexpected results based upon Example 1 and 2 of record (see, e.g., Reply filed 4/30/2026 at 14 at § 3 to page 20 at final ¶), acknowledges the Examiner’s response of record (see, e.g., Reply filed 4/30/2026 at 15 at 1st ¶ to page 20 at final ¶), and disputes the Examiner’s position that the proffered data is not commensurate in scope with the claimed invention (see, e.g., Reply filed 4/30/2026 at 17 at 2nd full ¶). Here, claim 1 is representative of the broadest claim scope presently claimed, and recites a sustained release formulation comprising “a single emulsion of condensed ed particles in an aqueous continuous phase” (presumably “oil-in-water” emulsion), wherein the particles comprise any salt form of zilucoplan and any PLGA polymer comprising a poly lactic acid and poly glycolic acid ratio of “from about 25:75 to about 75:25”, and wherein the any salt form of zilucoplan used may be present at a loading range of “about 36% to about 38%” (see claim 1). Notably, claim 1
does not recite nor require PVA;
does not recite nor require RESOMER®502H;
does not recite nor require acid-terminated PLGA;
does not recite nor require PLGA with a 7k-17k MW;
does not recite nor require product-by-process steps requiring 1 g: 10 mL PLGA:DCM with PVA present.
Furthermore, Example 1 is limited to “36-37.5%”, whereas “about 36% to about 38%” is understood to encompass the range of 28.8% to 45% (i.e., about is ±20% of a stated number). Therefore, the instant claims are vast, highly varied, and no represented by embodiments tested at instant Examples 1-2 because zero embodiments were reduced to practice
lacking the specifics of RESOMER®502H were tested (i.e., acid-terminated, 7k-17k MW, PLGA with 50:50 ratio of poly lactic acid and poly glycolic acid);
lacking PVA were tested;
lacking 50:50 ratio of poly lactic acid and poly glycolic acid; or otherwise
made using a process not requiring 1 g: 10 mL PLGA:DCM with PVA present.
If such limitations represent essential elements required to achieve the recited hoped-for and expected range of “about 36% to about 38%”, then such elements should be clearly recited at instant claim 1. To date, zero evidence commensurate in scope with the pending claim scope, as required by MPEP § 716.02(d) has been placed on record, and therefore the proffered data is not commensurate in scope with the pending claims. In the absence of such data, the proffered data continues to fail to satisfy MPEP § 716.02(d). On this basis alone, no unexpected results commensurate in scope with the requirements of MPEP § 716.02 and sufficient to rebut prima facie obviousness have been established on record.
Allegations that Examples 1 and 2 satisfy the requirements of MPEP § 716.02(d)(II) and establish criticality of range: It is the Examiner’s understanding that Applicant again alleges the existence of unexpected results based upon Example 1 and 2 of record (see, e.g., Reply filed 4/30/2026 at 14 at § 3 to page 20 at final ¶), acknowledges the Examiner’s response of record (see, e.g., Reply filed 4/30/2026 at 15 at 1st ¶ to page 20 at final ¶), and disputes the Examiner’s position that the proffered data does not provide evidence of criticality of range as required by MPEP 716.02(d) (see, e.g., Reply filed 4/30/2026 at 19-20 at bridging ¶, 20 at final ¶). Criticality of range is discussed at MPEP 716.02(d)(II), which states
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)
Here, the claimed range of “about 36% to about 38%” and “from about 25:75 to about 75:25” recite the term “about”, which is understood to mean ±20% of a value. Accordingly, “about 36% to about 38%” is understood to encompass the range of 28.8% to 45%; similarly, the range of “about 25:75 to about 75:25” includes 90:10 to 10:9018. Accordingly, in order to establish criticality of range, “applicants should compare a sufficient number of tests both inside and outside the claimed range”. Here, zero species were tested and disclosed that were loaded above 37.5, which is not “outside the claimed range” (see, e.g., Spec. filed 10/21/2021 at ¶[0274]). Furthermore, zero PLGA were tested other than RESOMER®502H (50:50). Therefore, no examples were tested outside the claimed range. Accordingly, zero evidence of record supports a determination of criticality of range commensurate in scope with the recited limits of instant claim 1. Oddly, Applicant acknowledges that 37.5% was the “highest allowable load before burst values became excessive”, but fails to identify how this limit is reflected by the limitations of instant claim 1 (see, e.g., Reply filed 4/30/2026 at 19-20 at bridging ¶, 20 at final ¶). Accordingly, zero evidence criticality of range has been placed on record commensurate in scope with MPEP §§ 716.02(a), (b), and (d). On this basis alone, no unexpected results commensurate in scope with the requirements of MPEP § 716.02 and sufficient to rebut prima facie obviousness have been established on record.
Accordingly, all arguments pertaining to allegations of unexpected results have been fully considered, but found not persuasive for the reasons set forth above. At this time, zero evidence of any unexpected results commensurate in scope with the requirements of MPEP § 716.02 have been placed on record.
The recitation of “about 36% to about 38%” Is Not a Functional Limitation
Applicant’s reliance upon the recitation “about 36% to about 38%” is misplaced because this limitation does not correspond to a limiting step or structure that differentiates the claim scope over the prior art: The recitation of “about 36% to about 38%” is understood to require that level of drug loading in the claimed product, but this does not appear to be how the Applicant is interpreting the limitation. Rather, it is the Examiner’s impression that Applicant is alleging that this result was not achievable or enabled by the prior art in the absence of unknown structures or unspecified product-by-process steps first discovered by the Applicant. If this is correct, then Applicant is advised that the recitation of ranges is not equivalent to or synonymous with a structural limitation.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding achieving a drug loading of “about 36% to about 38% by weight”: It is the Examiner’s understanding that Applicant is alleging that the prior art is not fully enabled or operable to achieve a drug loading amount of Zilucoplan within a single emulsion at “about 36% to about 38% by weight” (see, e.g., Reply filed 4/30/2026 at 10-11 at bridging ¶, 11 at 1st full ¶ to 11-12 at bridging ¶; see also id. at 12 at § 2 to page 14 at 1st partial ¶; see also preceding paragraph). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. Furthermore, Examiner directs Applicant to MPEP § 716.07, which states
Where the affidavit or declaration presented asserts that the reference relied upon is inoperative, the claims represented by applicant must distinguish from the alleged inoperative reference disclosure. In re Crosby, 157 F.2d 198, 71 USPQ 73 (CCPA 1946). See also In re Epstein, 32 F.3d 1559, 31 USPQ2d 1817 (Fed. Cir. 1994) (lack of diagrams, flow charts, and other details in the prior art references did not render them nonenabling in view of the fact that applicant’s own specification failed to provide such detailed information, and that one skilled in the art would have known how to implement the features of the references).
Here, the limitation at amended claim 1 (and 113) reciting “about 36% to about 38% by weight” is understood to merely recite a hoped-for and desired outcome commensurate in scope with the teachings of the prior art, which is fully satisfied by the prior art’s teaching that drugs may be loaded at 1-57% (w/w). However, claim 1 does not recite nor require PVA, excipients, acid-terminated PLGA within a particular weight range, etc., etc. Accordingly, if Applicant means to rely upon the range as a functional limitation requiring steps and structures not taught by the prior art, this is not persuasive. Accordingly, to establish that the prior art is not operable or enabling, MPEP § 716.07 requires a showing that the recited elements at instant claim 1 (i.e., any PLGA with any ratio of lactic:glycolic within claim 1, with any salt of Zilucoplan, in any single emulsion--including hydrogels templates) are insufficient to achieve the drug-loading range of “about 36% to about 38% by weight” utilizing the methodologies of the prior art. However, such a showing appears impossible in view of the presently claimed invention, because such evidence would also establish that the full scope of instant claim 1 was not enabled; therefore, presenting evidence of lack of enablement commensurate with instant claim 1 would likely raise scope of enablement issues under 35 USC §112(a). Furthermore, if the structures required to enable such drug-loading ranges amount to PVA, then such structures were already taught and known in the prior art.
Conclusion
Examiner notes that examination could be facilitated by evidence commensurate in scope with the requirements of MPEP § 716.02, showing criticality of range and statistically significant data commensurate in scope with the instant claims.
Examiner notes that conclusory statements in the absence of objective supporting evidence cannot take the place of evidence on the instant record.
Accordingly, all arguments raised by the Applicant have been fully considered but not found persuasive for the reasons set forth above or are otherwise rendered moot in view of the revised rejection. All revisions were necessitated by Applicant’s amendments.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new or revised 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Zilucoplan (a.k.a., RA101495 or R3193) is a prior art element taught and disclosed by WO2015/191951A2 (Dec. 17, 2015; cited in previous action; see, e.g., WO’941 at Tables on 60 and 100, disclosing SEQ ID NO: 194 as “R3193”, having the structure [cyclo(l,6)] Ac-K-V-E-R-F-D-(N-Me)D-Tbg-Y-azaTrp-E-Y-P-Chg-B28; see also id. at ¶[00268], reducing to practice R3193; see also id. at Substance Table on 156 at Substance 194, identifying it as CAS NO. 1841136-73-9).
2 see, e.g., Search notes showing PubChem Search for 1841136-73-9, 2 pages, created 5/16/2018, also available at https://pubchem.ncbi.nlm.nih.gov/#tab/sidsrcname=ChemIDplus&query=1841136-73-9&input_type=text (last visited 11/15/2024).
3 Cited in Requirement mailed 5/23/2024.
4 Mäder, “RESOMER® - Biodegradeable Polymers for Sutures, Medical Devices, Drug Delivery Systems and Tissue Engineering.”, Material Matters, vol. 6(3):62-66 (2011); hereafter “Mader”.
5 Mäder, “RESOMER® - Biodegradeable Polymers for Sutures, Medical Devices, Drug Delivery Systems and Tissue Engineering.”, Material Matters, vol. 6(3):62-66 (2011); hereafter “Mader”; cited in previous action.
6 Han et al., Biodegradable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading. Front Pharmacol. 2016 Jun 28;7:185. doi: 10.3389/fphar.2016.00185. PMID: 27445821; PMCID: PMC4923250; hereafter “Han”; cited in Requirement mailed 5/23/2024; hereafter “Han”; cited in previous action.
7Acharya et al., The hydrogel template method for fabrication of homogeneous nano/microparticles. J Control Release. 2010 Feb 15;141(3):314-9. doi: 10.1016/j.jconrel.2009.09.032. Epub 2009 Oct 12. PMID: 19822178; cited in previous action.
8 Mäder, “RESOMER® - Biodegradeable Polymers for Sutures, Medical Devices, Drug Delivery Systems and Tissue Engineering.”, Material Matters, vol. 6(3):62-66 (2011); hereafter “Mader”; cited in previous action.
9 Han et al., Biodegradable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading. Front Pharmacol. 2016 Jun 28;7:185. doi: 10.3389/fphar.2016.00185. PMID: 27445821; PMCID: PMC4923250; hereafter “Han”; cited in Requirement mailed 5/23/2024; hereafter “Han”; cited in previous action.
10Acharya et al., The hydrogel template method for fabrication of homogeneous nano/microparticles. J Control Release. 2010 Feb 15;141(3):314-9. doi: 10.1016/j.jconrel.2009.09.032. Epub 2009 Oct 12. PMID: 19822178; cited in previous action.
11 see, e.g., WO’951 at [00133], [00261], defining acronyms such as Chg (i.e., cyclohexylglycine).
12 see, e.g., WO’951 at [00133], defining “B28” as N-epsilon-(PEG24-gamma-glutamic acid-N-alpha-hexadecanoyl)Lys.
13 As noted in the claim interpretation section, the claim 1 phrase “a single emulsion of condensed particles in an aqueous continuous phase” has been reasonably interpreted on record to mean single oil-in-water emulsion (see, e.g., Spec. filed 10/21/2021 at ¶[0271]). Therefore, this limitation was understood to require that the particles are suspended in an aqueous solution (see, e.g., Action mailed 1/15/2026 at 5-6). Critically, Applicant did not specifically dispute this interpretation in the most recent response (see, e.g., Reply filed 4/30/2026, passim).
14 See previous footnote.
15 See also Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945) at 335, noting that "[r]eading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle."
16 See also KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007), noting that "[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
17 see, e.g., US20170333304A1 at ¶¶[0034], [0131], referring to “the water/oil ratio when the hydrogel particles are made with a single-emulsion technique” and “hydrogel particles fabricated by single-emulsion technique”).
18 75*(0.2) +75 is 90.
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