DETAILED ACTION
Status of the Claims
Claims 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42-47, 49, 51, 63, 66, 67, 80 and 88 are pending in the instant application. Claims 44-46 have been withdrawn based upon Restriction/Election. Claims 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80 and 88 are being examined on the merits in the instant application.
Request for Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/04/2026 has been entered.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.
Priority
The instant Application the U.S. entry of PCT/US2021/018806 filed 02/19/2021 and claims priority to U.S. Provisional Application No. 62/978,641 (hereafter ‘641) filed 02/19/2020.
The U.S. effective filing date for claims 1-2, 9, 11, 13, 14, 19, 23, 27, 31, 33, 34, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80, 85 and 88 has been determined to be 02/19/2020, the filing date of ‘641. The U.S. effective filing date for claims 16, 20 and 35 has been determined to be 02/19/2022, the filing date of PCT/US2021/018806. The examiner finds no support for “magnesium chloride” or “potassium nitrate” (instant claim 16), or phospholipids (instant claim 20 & 34), “or combinations thereof” (instant claims 16, 20, & 34).
Information Disclosure Statement
The information disclosure statements submitted on 06/04/2026 was filed before the mailing date of the first office action on the merits, subsequent to the above discussed RCE. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
Claim Objections
Claims 44-46 are objected to because of the following informalities: The claims have been withdrawn and status identifiers should indicate the same (MPEP §714(II)(C)). Appropriate correction is required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80 and 88 remain rejected under 35 U.S.C. 103 as being unpatentable over COFFMAN (WO 2019/023392 A1; published 31-JAN-2019) in view of Sah et al. (“Recent Trends in Preparation of Poly(lactide-co-glycolide) Nanoparticles by Mixing Polymeric Organic Solution with Antisolvent,” 2015; Hindawi Publishing Corporation; Journal of Nanomaterials, Volume 2015, Article ID 794601, pages 1-22); KUMAR (US 2012/0258914; published October, 2012) and Liu et al. (“Microfluidic-assisted fabrication of carriers for controlled drug delivery,” 2017, RSC; Lab on a Chip, Vol. 17, pp. 1856-1883).
Applicants Claims
Applicant claims a method of forming particles, the method comprising: (a) providing a first liquid comprising a therapeutic biologic and a solvent; (b) contacting the first liquid with a second liquid, thereby forming liquid droplets comprising the therapeutic biologic; (c) contacting the liquid droplets with a third liquid, thereby allowing the liquid droplets to dry; and (d) removing the first liquid, second liquid, and third liquid, thereby forming particles comprising a therapeutic biologic, wherein the circularity of a plurality of the particles is from about 0.80 to about 1.00 after removing the first liquid, second liquid, and third liquid." (instant claim 1),
Determination of the scope
and content of the prior art (MPEP 2141.01)
COFFMAN teaches "The invention provides methods for the preparation of particles including one or more agents, e.g., therapeutic or diagnostic agents. The particles can be formed by creating droplets of a first liquid, e.g., including an agent, and removing the first liquid, e.g., through its dispersal in a second liquid and/or evaporation, to solidify the droplets. Advantageously, the process of forming the particles does not significantly alter the structure or activity of the agents and may enhance the stability of the agents. For example, the particles may be stored for long periods of time without significant loss of activity, and in some embodiments, with out the need for refrigeration. These particles may be used to generate stabilized pharmaceutical compositions for storage or other logistical purposes, pharmaceutical suspensions, pharmaceutical powder formulations (e.g., inhalable powders, injectable powders), creams or other topical pastes, nutraceuticals, or cosmetics." (abstract, see whole document).
COFFMAN teaches that the: "Droplets of the invention can be formed through any of several techniques that are known in the art. These include rotary atomization, pneumatic atomization, ultrasonic atomization, sonic atomization, vibrating mesh nebulization, jet atomization, microfluidic droplet generation, electrospray, or homogenization. The droplets include a first liquid and one or more agents, e.g., a therapeutic and/or diagnostic agent. The concentration of any agent, e.g., a therapeutic or diagnostic agent, [ ... ]." (p. 12, last paragraph). The first liquid being aqueous or organic solvent, the aqueous solvent being water which can further include a buffer, a carbohydrate, a salt and a surfactant, among others (p. 13, 2nd paragraph).
COFFMAN teaches that: "In some embodiments, droplets are formed using a microfluidic device (FIG. 6). In some such embodiments, a microfluidic source 1 produces droplets 2, wherein the first liquid 11 is co-flowed with an at an least partially immiscible liquid 12, i.e., a third liquid, to form droplets 2. The droplets 2 can be collected in a vessel 4 containing a second liquid 13, in which they dry to form particles 5. In some embodiments, the liquids 12 and 13 are different but miscible. In some embodiments, the first liquid is co-flowed directly with the second liquid, such that an intermediate liquid 12 is obviated. Droplets may be formed by the traditional method, whereby flow in the microfluidic system remains Stokesian, typified by a low Reynolds number, or through inertial microfluidic technologies ([...])." (p. 24, lines 14-21; Figure 6). The examiner notes that “flow in the microfluidic system remains Stokesian, typified by a low Reynolds number” implies laminar flow which is characteristic of a low Reynold’s number (instant claim 47)(MPEP §2144.01).
COFFMAN teaches that: "Cohesive forces (e.g., interfacial tension) on the droplet surface in the second liquid may pull the droplets into a spherical shape which is maintained during the course of drying. Sphericity of the particles may range from 0.1 to 1, e.g., be at least 0.2, 0.4, 0.6, or 0.8. This process can result in uniform particles with high sphericity (>0.9) and roundness." (p. 26, lines 17-20)(instant claim 1, item d - "the circularity […] from about 0.8 to about 1.00"; instant claims 1 & 80).
COFFMAN teaches that: "The methods disclosed herein have been utilized in separate instances to prepare particles including at least one of several agents, e.g., whole human lgG or bovine lgG, or one of several monoclonal antibodies. Various analytical techniques were applied to assess the physical characteristics of the particles themselves as well as the structural and functional properties of the processed agents. Scanning electron microscopy and associated image analysis were used to study the particle morphology and size distribution, respectively. Various morphologies were achieved by controlling the properties of the first liquid and/or the second liquid. In some instances, the processing conditions conferred smooth particles of high sphericity and/or facile control of the mean particle size over a broad range with low dispersity." (p. 34, l81 paragraph)(instant claim 1, "a therapeutic biologic"; instant claim 2, elected species – “an antibody”).
COFFMAN discloses Example 12 in which: "Human lgG powder was reconstituted in deionized water to a protein concentration of approximately 20 mg/ml. The solution was desalted and a quantity of Tween 20 (5mg/ml) was added, after which it was atomized and collected with a stainless steel vessel containing 200 ml of butyl acetate held near room temperature under conditions of gentle stirring. Approximately 2 ml of feed solution was processed. After primary desiccation, particles were collected, washed, and vacuum dried to remove residual liquid. SEM images revealed identifiable particulate matter(FIGS. 19A-19B)." [emphasis added](p. 40, Example 12)(instant claim 21)(MPEP 2144.05(I)).
COFFMAN claims: "A method of forming particles, the method comprising: providing droplets comprising a first liquid and an therapeutic or diagnostic agent; contacting the droplets with a second liquid, wherein the droplets float or do not float on the second liquid; and allowing the droplets to dry, thereby forming the particles." [emphasis added](claim 4), the therapeutic or diagnostic agent including antibodies (claim 87), the first liquid including water (claims 13-14), the second liquid is an organic solvent such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, amyl acetate, among others (claims 43-44 ), and further washing the particles with a third liquid which is on organic solvent such as amyl acetate, butyl acetate, ethyl acetate, methyl acetate, propyl acetate, among others (claims 53-55)(instant claims 49, 51, elected species of 3rd liquid). COFFMAN teaches the first liquid may further include a surfactant such as polysorbate (p. 2, lines 11-12 & 27)(instant claims 13 & 20, elected species of first liquid). COFFMAN teaches that the second liquid can include an organic solvent (p. 3, lines 10-11), including ethyl acetate (p. 3, lines,14 & 20), and can include surfactants (p. 4, lines 21-22) which can includes polysorbate (p. 4, lines 33-34)(instant claims 31, 33, 34, 35; elected species of second liquid – ethyl acetate and polysorbate). COFFMAN teaches that: “The method may further include washing the particles with a third liquid. In certain
embodiments, the third liquid is an organic solvent.” including propyl acetate (p. 5, lines 25-26 & 33)(instant claims 49, 51; elected species of 3rd liquid – propyl acetate). And that: “The third liquid may be removed through evaporation or lyophilization.” (p. 4, line 35, instant claim 66). COFFMAN claims that: “the carbohydrate is dextran, trehalose, sucrose, agarose, mannitol, lactose, sorbitol, or maltose.” (claim 57)(instant claims 13-14).
COFFMAN teaches that: “In some embodiments, the particles are removed from the second liquid via centrifugation, sieving, filtration, magnetic collection, solvent exchange, or decanting.” (p. 25, lines 9-10)(instant claim 63). COFFMAN teaches that: “The particles can be subjected to one or more secondary desiccation steps after separation from the second liquid. Such steps can be utilized to remove washing liquid, as stated previously, and/or to modulate residual quantities of the first liquid in the particles. Exemplary methods of secondary desiccation include vacuum drying with or without application of heat, lyophilization, fluidized bed drying, and slurry spray drying.” (p. 25, lines 30-34). The examiner notes that fluidized bed drying includes “contacting the particles with a stream of gas” (instant claim 67)(MPEP §2144.01).
COFFMAN teaches that: “The particles may include one or more agents, e.g., therapeutic or diagnostic agents. The particles can have diameters from 0.1 to 1000 μm, e.g., 0.1 to 90 μm, 90 to 230 μm, or 0.1 to 1 μm.” (p. 26, lines 10-11)(instant claim 88 – MPEP 2144.05(I)).
COFFMAN teaches that: “In some instances, the processing conditions conferred smooth particles of high sphericity and/or facile control of the mean particle size over a broad range with low dispersity.” [emphasis added](p. 34, lines 8-10)(instant claim 85).
COFFMAN claims that: “The method of any one of claims 1-49, wherein the first liquid has a viscosity from 0.01 cP to 10,000 cP.” (claim 50), and that: “The method of any one of claims 1-49, wherein the second liquid has a viscosity from 0.01 cP to 10,000 cP.” (claim 51). The examiner notes that 1 cP is approximately equivalent to 1 mPa⸱s, therefore the range defined by claims 50 & 51 of COFFMAN encompasses the claimed viscosity of less than about 10 mPa⸱s (instant claims 27 & 38)(MPEP 2144.05(I)).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of COFFMAN is that COFFMAN does not expressly teach static mixing.
KUMAR teaches a coacervation process (title, see whole document), and particularly that: “Methods of forming compositions for the sustained release of water soluble active agents, including biologically active polypeptides and products produced by the process are described. Improved product characteristics and ease of scale-up can be achieved using a novel coacervation process wherein at least one coacervation agent is added to the mixture comprising the active agent and the polymer in at least two distinct stages.” (abstract).
KUMAR teaches that: “In a particular embodiment, the first coacervation agent addition is made to take place in a static mixer. In preferred embodiment, the final addition of coacervation agent is made to take place in a static mixer. In yet another embodiment, the final addition of coacervation agent is made to take place in a static mixer and the resulting mixture is made to flow through an assembly comprising hollow tubing to provide residence time and some degree of mixing, and a final static mixer before discharging into a quench tank containing a hardening agent.” ([0024])(instant claims 42-43, static mixing).
Sah et al. teaches that: “Static mixers have been sought to overcome the obstacles encountered with traditional mixing devices. Static mixers have a series of mixing elements that are arrayed inside a tube, a pipe, or a column. Since static mixers have no moving parts, they are known as motionless mixers. External pumps are used to move liquid streams through helically- or blade-designed mixing elements. Inside static mixers, liquid streams undergo flow division, radial momentum transfer, and inertia reversal. As a consequence, static mixers can create very fine dispersions or stable emulsions with uniform sizes. A number of static mixers are commercially available in the market: Ross motionless mixers, Admixer inline static mixers, Koflo static mixers, Chemineer Kenics KM static mixers, JLS Samhwa static mixers, and Sulzer SMX mixers.” (p. 11, col. 2, 2nd paragraph). Sah et al. further teaches that: “Static mixers tend to produce emulsion droplets with narrower size distributions than do mechanical agitators. Other merits of static mixers over typical mechanical mixers include uniform shear across whole liquid streams, short residence time of liquid streams inside the mixers, predictable performance, and easy adaptation for scale-up. In particular, static mixers use significantly less energy to generate emulsion droplets than high-shear/high-energy/high-pressure homogenizers. Furthermore, static mixers can be easily dissembled for cleaning, maintenance, and sterilization.” (p. 11, col. 2, 4th paragraph).
Liu et al. teaches that: “Droplet-based microfluidics is an important subcategory of the microfluidic technologies, which manipulates immiscible phases to generate droplets. The droplet phase is identified as dispersed phase, while the medium phase is termed as continuous phase. In general, the droplet size is controlled by adjusting the flow rates and ratios of the two phases; however, it is also affected by the viscosity of the dispersed phase, the channel and orifice diameter, flow regimes, and other parameters. Droplet microfluidics is a versatile technique to produce micro-sized single and multiple emulsions, because of its ability to produce droplets with various degrees of complexity. Droplet-based microfluidics techniques are widely used in, for example, particle fabrication, encapsulation, sorting, and cell analysis. It represents also a very useful technique for the fabrication of advanced drug delivery systems with precisely controlled loading and release of therapeutics.” [emphasis added](p. 1859, §2.2, 1st paragraph; see whole document).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce microparticles including an antibody using the method of COFFMAN, and to conduct the mixing with a static mixer as suggested by KUMAR, static mixers having advantages, as suggested by Sah et al., such as producing droplets with a narrow size distribution (relative to mechanical agitators), easy of operation and scale-up, using significantly less energy to generate emulsion droplets, and can be easily dissembled for cleaning, maintenance, and sterilization. Additionally, it would have been prima facie obvious that the droplet formation process described by COFFMAN would have encompassed emulsion formation, as suggested by Liu et al., and COFFMAN, at least in Examples 63 and 64. The examiner further notes that, in the art to which the invention pertains, ethyl acetate is well-known as an organic solvent with high biocompatibility (see, e.g., Moreno et al.1, p. 165, col. 1, 2nd paragraph).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary level of skill to utilize a static mixer for production of the particles according to COFFMAN. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
Response to Arguments:
Applicant's arguments filed 11/18/2025 have been fully considered but they are not persuasive.
Applicant argues that: “It is noted that liquid 12 in FIG. 6 of Coffman is part of the droplet generation apparatus; it is not the continuous phase of a stable emulsion. The properties of liquid 12 are chosen to control the size and frequency of droplet generation, and not to create a stable mixture. In contrast, as recited in present claim 1, ‘liquid droplets of the first liquid dispersed in the second liquid’ are formed, and subsequently particles comprising a therapeutic biologic are formed ‘after removing the first liquid, second liquid, and third liquid.’” (p. 8, 3rd paragraph).
In response the examiner argues that COFFMAN clearly teaches “FIG. 6 is a scheme showing a microfluidic droplet source 1 that produces droplets 2. The first
liquid 11 is co-flowed with an at least partially immiscible liquid 12 to form the droplets 2 that are collected by a vessel 4 containing the second liquid 13.” (p. 12, lines 1-3). The description “at least partially immiscible liquid” clearly includes immiscible liquids. As one of ordinary skill would have clearly understood the droplets are formed by an emulsion process where the droplets are the dispersed phase (liquid 11) and dropped or injected into the continuous phase (liquid 12) and collected in a third phase (liquid 13) which can be the same of different from the dispersed phase (liquid 12). Additionally, COFFMAN clearly teaches examples 63 and 64 including “a continuous phase consisting of neat cottonseed oil” and a “proteinaceous dispersed phase” (Human IgG in deionized water – concentration ~50 mg/mL – instant claim 23).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant further argues that: “Claim 1, as amended, further comprises contacting the pre-formed emulsion with a third liquid (to allow the droplets to dry). This allows better control of drying rate, which creates a technical advantage that results in better particle circularity. In Coffman's method, the drying rate is governed by the properties of the collection bath (second liquid 13, FIG. 6 of Coffman). In contrast, in present claim 1, a separate third liquid is actively introduced to the emulsion, providing an additional control over the solvent extraction from the droplets. As demonstrated, for example, in Example 1 of the instant Specification, the flow rate of the emulsion, the flow rate of the third liquid, and the mixing dynamics between the two may be precisely tuned to achieve particles with high circularity (e.g., 0.915). In contrast, Coffman's method of simply collecting droplets in a bath lacks this degree of active control over the drying process.” (p. 8, last paragraph through p. 9 line 2).
In response the examiner argues that: COFFMAN clearly teaches that: "Cohesive forces (e.g., interfacial tension) on the droplet surface in the second liquid may pull the droplets into a spherical shape which is maintained during the course of drying. Sphericity of the particles may range from 0.1 to 1, e.g., be at least 0.2, 0.4, 0.6, or 0.8. This process can result in uniform particles with high sphericity (>0.9) and roundness." (p. 26, lines 17-20)(instant claim 1, item d - "the circularity […] from about 0.8 to about 1.00"; instant claims 1 & 80).
Additionally, the rejected claims are not limited to Example 1, therefore Applicants argument is not considered commensurate with the rejected claims. Particularly, the mixing in Example 1 is achieved by two “PEEK Y-connectors” whereas the mixing (emulsification), in contrast instant claim 1 is generic to any method(s) of forming an emulsion, instant claim s 42 and 43 reciting further defining this limitation, none of which appear to be limited to a series of “PEEK Y-connectors” as in Example 1 of the instant Specification.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80 and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims, of copending Application Nos. 19/313,479 (claims 1-18; hereafter ‘479) and 19/183,458 (claims 1-10, and 14-20; hereafter ‘458) in view of COFFMAN, Sah et al. and KUMAR (as cited above).
Instant claim 1 is discussed above.
Copending ‘479 claim 1 recites a method of forming particles, the method comprising: (a) providing an aqueous first liquid comprising a therapeutic biologic; (b) contacting the aqueous first liquid comprising the therapeutic biologic with an organic second liquid by a continuous process, thereby forming a mixture comprising aqueous liquid droplets, wherein the aqueous liquid droplets comprise the therapeutic biologic; (c) dehydrating the aqueous liquid droplets in the mixture; and (d) removing the aqueous first liquid and organic second liquid from the mixture,
thereby forming particles comprising the therapeutic biologic, wherein the circularity of the particles is from about 0.80 to about 1.00 after removing the aqueous first liquid and organic second liquid from the mixture, wherein the concentration of the therapeutic biologic in the aqueous first liquid is about 10 mg/mL to about 500 mg/mL, wherein the aqueous first liquid has a viscosity of less that about 25 mPa⸱s, and wherein the continuous process of step b), comprises continuous membrane emulsification, continuous homogenization, continuous impinging jet mixing, continuous static mixing, or a combination thereof.
‘458 claim 1 recites a method of forming particles by a continuous process, the method comprising: (a) providing an aqueous first liquid comprising a therapeutic biologic; (b) providing an organic second liquid; (c) dispersing the aqueous first liquid into the organic second liquid, thereby forming aqueous liquid droplets in the organic second liquid, wherein the aqueous liquid droplets comprise the therapeutic biologic; (d) dehydrating the aqueous liquid droplets by maintaining the aqueous liquid droplets in the organic second liquid to form particles comprising the therapeutic biologic, wherein the steps of dispersing and dehydrating the aqueous liquid droplets proceed without interruption for a period of about 1 second to about 60 seconds, about 1 minute to about 60 minutes, about 1 hour to about 24 hours, about 1 day to about 7 days, or about 1 week to about 4 weeks; (e) separating the particles from the organic second liquid; and (f) further dehydrating the particles to achieve an average residual moisture level of less than 10% by weight.
The difference between the instantly rejected claims and the claims of copending ‘479 and ‘458 is that the claim of copending ‘479 and ‘458 do not expressly require static mixing.
COFFMAN teaches their invention provides methods for the preparation of particles including one or more agents, e.g., therapeutic or diagnostic agents, as discussed above and incorporated herein by reference.
KUMAR teaches a coacervation process including a static mixer, as discussed above and incorporated herein by reference.
Sah et al. teaches particular advantages of static mixers, as discussed above and incorporated herein by reference.
It would have been prima facie obvious before the effective filing date of the claimed invention that the instantly rejected claims are an obvious variant of the claims of copending ‘479 and/or ‘458 because the instant claims are directed to producing particles by methods substantially identical to the claims of ‘618 and/or ‘458. The skilled artisan would have been motivated to modify the claims of copending ‘479 and/or ‘458 and produce the instantly rejected claims for the advantages of stating mixing as taught by KUMAR and Sah et al. Furthermore, the skilled artisan would have had a reasonable expectation of success in producing the invention of the instantly rejected claims because it would have required no more than an ordinary level of skill to utilize a static mixer in production of the particles of ‘479 and/or ‘458.
This is a provisional obviousness-type double patenting rejection.
Claim 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80 and 88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, of U.S. Patent No. 12,377,050 (hereafter ‘050) in view of COFFMAN, Sah et al. and KUMAR (as cited above).
Instant claim 1 is discussed above.
Copending ‘618 claim 1 recites a method of forming particles, the method comprising: (a) providing an aqueous first liquid comprising a therapeutic biologic; (b) contacting the aqueous first liquid comprising the therapeutic biologic with an organic second liquid by a continuous process, thereby forming a mixture comprising aqueous liquid droplets, wherein the aqueous liquid droplets comprise the therapeutic biologic; (c) dehydrating the aqueous liquid droplets in the mixture; and (d) removing the aqueous first liquid and organic second liquid from the mixture,
thereby forming particles comprising the therapeutic biologic, wherein the particles comprise less than about 10% internal void spaces and the circularity of the particles is from about 0.80 to about 1.00 after removing the aqueous first liquid and organic second liquid from the mixture, wherein the concentration of the therapeutic biologic in the aqueous first liquid is about 10 mg/mL to about 500 mg/mL, wherein the aqueous first liquid has a viscosity of less that about 10 mPa-s, and wherein the continuous process of step (b), comprises continuous membrane emulsification, continuous homogenization, continuous impinging jet mixing, continuous static mixing, or a combination thereof.
The difference between the instantly rejected claims and the claims of ‘618 and ‘050 is that the claims of ‘050 do not expressly require static mixing.
COFFMAN teaches their invention provides methods for the preparation of particles including one or more agents, e.g., therapeutic or diagnostic agents, as discussed above and incorporated herein by reference.
KUMAR teaches a coacervation process including a static mixer, as discussed above and incorporated herein by reference.
Sah et al. teaches particular advantages of static mixers, as discussed above and incorporated herein by reference.
It would have been prima facie obvious before the effective filing date of the claimed invention that the instantly rejected claims are an obvious variant of the claims of ‘050 because the instant claims are directed to producing particles by methods substantially identical to the claims of ‘050. The skilled artisan would have been motivated to modify the claims of ‘050 and produce the instantly rejected claims for the advantages of stating mixing as taught by KUMAR and Sah et al. Furthermore, the skilled artisan would have had a reasonable expectation of success in producing the invention of the instantly rejected claims because it would have required no more than an ordinary level of skill to utilize a static mixer in production of the particles of ‘050.
Response to Arguments:
Applicant's arguments filed 11/18/2025 have been fully considered but they are not persuasive.
Applicant argues that: “Applicant respectfully traverses. As discussed above in connection with the rejection under 35 U.S.C. 103, one ordinary skill in the art would not reasonably predict or expect to arrive at the method as claimed in view of Coffman et al., Sah et al. and Kumar et al.” And “Accordingly, it would not have been obvious to one of ordinary skill in the art to combine the claims of any of the cited reference patents or patent applications of the instant double patenting rejections with Coffman et al., Sah et al. and Kumar et al. Applicant respectfully submits that the instant claims are patentably distinct from the claims of each of the cited patents or patent applications.” (pp. 9).
In response the examiner argues that the arguments above were not convincing with the rejection under 35 U.S.C. 103, and therefore are not convincing here.
Conclusion
Claims 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80 and 88 are pending and have been examined on the merits. Claims 44-46 are objected to; claims 1-2, 9, 11, 13, 14, 16, 19, 20, 23, 27, 31, 33-35, 38, 42, 43, 47, 49, 51, 63, 66, 67, 80 and 88 are rejected under 35 U.S.C. 103; and claims are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims, of USPN 12,377,050 and copending Application Nos. 19/183,458 and 19/313,479. No claims allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IVAN A GREENE whose telephone number is (571)270-5868. The examiner can normally be reached M-F, 8-5 PM PST.
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/IVAN A GREENE/Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
1 Moreno et al.; “Study of stability and biophysical characterization of ranibizumab and aflibercept,” 2016, ELSEVIER; European Journal of Pharmaceutics and Biopharmaceutics, Vol. 108, pp. 156-167.
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