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, 85 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 Claims 44-46 have been withdrawn based upon Restriction/Election.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, 85 and 88 are being examined on the merits in the instant application.
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All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.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 11/18/2025 was filed after the mailing date of the first office action on the merits, however, Applicant has indicated the appropriate fees (37CFR1.97(e)) have been paid. 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Claims 44-46 are objected to because of the following informalities: The claims have been withdrawn and status identifiers should indicate the same (MPEP §714(II)(C)).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, 85 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) and KUMAR (US 2012/0258914; published October, 2012).
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 claim 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).
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 COFFEE, 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.
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: “Applicant respectfully submits that the Office has not established a prima facie case of obviousness for combining the teachings of Coffman et al., Sah et al., and Kumar et al. in the manner set forth in the instant Office Action. Applicant's claim 1 recites that droplets are formed by contacting the first liquid with a second liquid, and a third liquid contacts the liquid droplets for drying the droplets, while Coffman discloses that droplets comprising a first liquid are contacted with a second liquid (e.g., claim 1) and the already-formed particles are washed with a third liquid (e.g., claim 53). In Applicant's claim 1, the particles are formed by removing the first liquid, second liquid, and third liquid. Further, as noted above, in Applicant's claim 1, the third liquid is used for drying the droplets, while in Coffman the third liquid is used for washing the particles.” (p. 8, 2nd paragraph).
In response the examiner argues that COFFMAN clearly 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 ([...])." [emphasis added](p. 24, lines 14-21; Figure 6). Figure 6 clearly shows three different liquids – 11, 12 and 13 – wherein “contacting the liquid droplets with a third liquid, thereby allowing the liquid droplets to dry” clearly occurs in Vessel 4. Therefore, Applicants argument is not convincing as the alleged missing subject matter is clearly taught by COFFMAN.
Applicant further argues that “As presented in paragraph [00379] of the instant application, for example, particles having a circularity of 0.915 were formed, starting with a water-in oil emulsion produced by mixing a dispersed phase (DP) (bovine serum albumin (BSA) prepared at 50 mg/mL in water) and a continuous phase (CP) (solution of heptane with 5 wt/vol% Span 80 surfactant) using a Y connector assembly, which provides evidence of nonobviousness of Applicant's claims. The combination of Coffman et al., Sah et al., or Kumar et al. does not provide a reasonable expectation of success for forming particles having a circularity of about 0.80 to about 1.00, as recited in Applicant's claim 1.” (p. 8, 2nd paragraph).
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). And more particularly 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 claim 80). The distinction between sphericity and circularity is clearly that the former is in three dimensions whereas the latter is in two dimensions, the latter being determined from analysis of a 2-D image (instant Specification p. 28, last three lines). The examiner takes the position that if a particle is spherical (3D) it is also circular (2D) because profile of a sphere is a circle (MPEP §2144.01).
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, 85 and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims, of copending Application Nos. 17/916,618 (Now US12,377,050) (claims 1-2, 8, 11, 28-29, 43-45, 48-49 and 52-56; hereafter ‘618) 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 ‘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.
‘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 ‘618 and ‘458 is that the claim of copending ‘618 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 ‘618 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 ‘618 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 ‘618 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, 85 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. 9-10).
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, 85 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, 85 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 No. 19/183,458. No claims allowed at this time.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to 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
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619