DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Amendments to the Specification, Drawings and Claims and Arguments/Remarks filed 23 December 2025, in response to the Office Correspondence dated 07 August 2025, are acknowledged.
The listing of Claims filed 23 December 2025, have been examined. Claims 18, 20, 22, 25, 26, and 28-39 are pending. Claims 18, 20, 25, 26, 28, and 35 are amended and are supported by the originally-filed disclosure. Claims 1-17, 19, 21, 23, 24, and 27 are canceled and new claims 36-39 have been added.
Information Disclosure Statement
The Information Disclosure Statement (IDS), filed 23 December 2025, is acknowledged and has been considered.
Response to Amendment
The Amendment filed has been entered.
Replacement Figures 1A and 1B have been reviewed and are acceptable. The drawing objection under 37 CFR § 1.84 is withdrawn. The amended title “Antibody-Loaded Polymeric Filaments for Implantable Drug Delivery Devices” is acceptable, and thus the title objection under 37 CFR § 1.72 is withdrawn.
The applicant has corrected the typographical error in claim 35, “depositing said heated a filament”. Accordingly, the claim objection is withdrawn.
Claims 21, 23-25, and 27 are canceled and as such prior rejections are considered moot. Accordingly, the § 112(b) rejection of those claims is moot. Independent claim 18 and dependent claims 20, 22, 25, 26, 28, and 36-39 now explicitly recite all weight percentages as “by weight of the filament.” Therefore, the ambiguity identified in the prior Office Action has been cured. The § 112(b) rejection is withdrawn. However, a new 35 U.S.C. § 112(b) rejection has been issued for amended claim 18, and therefore dependent claims as well, as outlined below.
Regarding the 35 U.S.C. § 102 rejection of claims 18, 20, 22, 26, and 28-32, the applicant’s arguments have been fully considered but are not persuasive. The applicant has not identified any structural or compositional limitation of claims 18, 20, 22, 26, or 28-32 that is not expressly or inherently disclosed by Trogden, therefore the § 102(a)(1) rejection of claims 18, 20, 22, 26, and 28-32 is maintained.
Regarding the 35 U.S.C. § 103 of claims 18 and 25, the applicant’s arguments against obviousness have been considered but are not persuasive, for the reasons set forth below in the Response to Arguments and as such, the § 103 rejection of claims 18 and 25 over Trogden in view of Vollrath is maintained.
Regarding the 35 U.S.C. § 103 of claims 18 and 33, the applicant argues that Schneider does not remedy alleged defects in Trogden. This argument is not persuasive and the § 103 rejection of claims 18 and 33 is maintained.
Regarding the rejection of claim 34 under 35 U.S.C. § 103 as being obvious over Trogden in view of Arrighi, the applicant argues that Arrighi does not cure deficiencies in Trogden. This argument is not persuasive and thus, the § 103 rejection of claim 34 is maintained.
Regarding the rejection of claim 35 under 35 U.S.C. § 103 as being obvious over Trogden in view of Schneider and in further view of Carlier, the applicant’s arguments regarding motivation and expectation of success are not persuasive. The applicant has not provided evidence of unexpected results or criticality, therefore, the § 103 rejection of claim 35 is maintained.
Newly added claims 36-39 recite narrowed compositional percentages and specific excipient combinations. These limitations do not confer patentability. Accordingly, claims 36-39 are rejected under 35 U.S.C. § 103 as obvious over Trogden in view of Vollrath and further in view of Arrighi, as detailed below.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 07 August 2025, since the art which was previously cited continues to read on the amended/newly cited limitations.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 18, 20, 22, 26, and 28-32 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Trogden (US8318169B2; published 27 November 2012).
Regarding instant claims 18, 20 and 22, Trogden Example 4 teaches a PLGA implant filament for sustained release of a therapeutic agent, exemplified as oligonucleotides but also explicitly includes antibodies (claims 2, 5 and 6; page 9, column 12, lines 60-67). The filament contained a freeze-dried therapeutic agent blended separately with an excipient fatty alcohol modifier [1-hexadecanol, 1-octadecanol, and 1-eicosanol specified in claim 3 are anionic surfactants and emulsion stabilizers] and 5% w/w polyethylene glycol 3350 (PEG-3350) and 85% w/w powdered PLGA (Resomer RG-752, Boehringer Ingelheim), wherein the PLGA polymeric carrier may be about 70-85% w/w (claim 1), thus teaching the limitations of instant claims 18, 20 and 22.
Regarding instant claim 26, Trogden teaches, “The drug delivery systems, such as the intraocular implants, can be monolithic, i.e. having the active agent or agents homogenously distributed through the polymeric matrix, or encapsulated, where a reservoir of active agent is encapsulated by the polymeric matrix.” (page 11, column 16, lines 43-47), incorporating the limitation of instant claim 26.
Regarding instant claim 28, Trogden teaches in Example 1, “Biodegradable implants are made by combining about 10-20% by weight of a therapeutic agent, such as those agents described above, about with 70-85% by weight of a biodegradable polymeric carrier, and about 5-10% by weight of a long chain fatty alcohol release modifier [stabilizer]...” (page 14, column 22, lines 6-10), resulting in a w/w antibody: stabilizer ratio range of from 1:1 to 4:1 that are encompassed within the range of the instant claim.
Regarding instant claim 29, Trogden teaches, “Drug delivery systems can be prepared where the center may be of one material and the surface may have one or more layers of the same or a different composition…” (page 12, column 17, lines 24-26), including the limitation of instant claim 29.
Regarding instant claims 30-32, Trogden teaches a drug delivery system layer thickness of about 0.1-1.0 mm [100-1000 μm] for ease of handling (page 12, column 17, lines 43-44), encompassing instant claim 30 range and further specifies that, “The drug delivery systems can be of any geometry…” (page 12, column 17, line 36), wherein hollow and solid internal architecture, structural shape and overall design are geometric aspects. Thus, the limitations of instant claims 30-32 are taught by Trogden.
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 18 and 25 are rejected under 35 U.S.C. § 103 as being obvious over Trogden (US8318169B2; published 27 November 2012) in view of Vollrath (Vollrath M, Engert J, Winter G. Long-term release and stability of pharmaceutical proteins delivered from solid lipid implants. Eur J Pharm Biopharm. 2017 Aug;117:244-255; published electronically 22 April 2017).
Trogden teaches the limitations of instant claim 18, as described above, from which instant claim 25 depends, however these claims are included in the rejection on the basis of the rejection of dependent claim 25.
Regarding instant claim 25, Trogden teaches the invention including a release modifier, wherein, “The release modifier of the present systems is preferably from about 1% to 30% by weight of the drug delivery system…In a preferred embodiment, the release modifier comprises from about 5% to about 15% by weight of the system.” (page 10, column 14, lines 24-29) and wherein, “Release modifiers are disclosed in U. S. Pat. No. 5,869,079.” (page 12, column 18, line 37) and can also function as stabilizers and further, “A formulation within the scope of our invention can comprise a drug, a polymeric carrier for the drug and a long-chain fatty alcohol release modifier. The drug delivery system can also comprise one or more additional drugs, polymer blends, fatty alcohol blends and excipients.” (page 7, column 7, lines 14-19).
The referenced patent US5869079A discloses, “The release modulator is an agent that alters the release of a drug from a biodegradable implant in a defined manner. It may be an accelerator or a retardant.” (page 5, column 2, lines 53-55), wherein, “Accelerators may be physiologically inert…sugars, e.g. monosaccharides such as fructose and glucose, disaccharides such as lactose, sucrose, or polysaccharides…Alternatively, the accelerator may be a physiologically active agent, allowing for a combined therapeutic formulation. The choice of accelerator in such a case will be determined by the desired combination of therapeutic activities.” (page 6, column 3, lines 7-16).
In addition to the teachings disclosed by Trodgen, Vollrath teaches an implantable sustained release drug delivery device comprising a monoclonal antibody IgG1 and fab-fragment Ranibizumab in freeze-dried matrix formulated in 10 mM histidine-HCl buffer with 10% α-trehalose (page 245, section 2. Materials and methods) dialyzed with the stabilizer hydroxypropyl-β-cyclodextrin (HP-β-CD) (page 245, section 2.1.1. Dialysis and exchange of stabilizing excipients). Thus, the instant claims are obvious in view of Trogden and more so in view of Vollrath.
Using a filament 5-15% (w/w) stabilizer including either a sucrose or trehalose disaccharide or the cyclic oligosaccharide hydroxypropyl-β-cyclodextrin would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, as a matter of routine formulation optimization as they were known at the time of the invention to be used as common excipients in the art to improve composition stability, as evidence by Vollrath.
Claims 18 and 33 are rejected under 35 U.S.C. § 103 as being obvious over Trogden (US8318169B2; published 27 November 2012) in view of Schneider (US20190358166A1; published 20 May 2019).
Trogden teaches the limitations of instant claim 18 (as described above), from which instant claim 33 depends, however this claim is included in the rejection as well on the basis of rejecting dependent claim 33.
Regarding instant claim 33, Trogden teaches, “Additionally, drug delivery system can be made by heat extrusion, cold press, solvent casting, melt casting, solvent evaporation and other known procedures.” (page 7, column 7, lines 27-29), wherein 3D printing was a known procedure at the time of the instant invention. Further, Trogden teaches, “Various techniques may be employed to produce the drug delivery systems described herein. Useful techniques include, but are not necessarily limited to, solvent evaporation methods, phase separation methods, interfacial methods, molding methods, injection molding methods, thermal extrusion methods, co-extrusion methods, carver press method, die cutting methods, heat compression, combinations thereof and the like.” (page 13, column 19, lines 27-34), wherein “combinations thereof and the like” can be interpreted broadly to include 3D printing.
In addition to the teachings disclosed by Trodgen, Schneider explicitly teaches, macromolecular drug [which includes antibodies] blended with a polymer to form a composition that may be in the form filaments, which may be shaped into the core using a variety of known shaping techniques, including three-dimensional printing [0042]. Thus, the instant claim is obvious in view of Trogden and more so in view of Schneider.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to use three-dimensional printing to for the filaments of the instant invention, as this was a process known at the time of the invention to be used in the art for the same purpose of producing filaments as evidence by Schneider.
Claim 34 is rejected under 35 U.S.C. § 103 as being obvious over Trogden (US8318169B2; published 27 November 2012) in view of Arrighi (Arrighi A, Marquette S, Peerboom C, Denis L, Goole J, Amighi K. Development of PLGA microparticles with high immunoglobulin G-loaded levels and sustained-release properties obtained by spray-drying a water-in-oil emulsion. Int J Pharm. 2019 Jul 20;566:291-298; published electronically 28 May 2019).
Regarding instant claim 34, Trogden teaches the process more generally as, “A method of making the present systems involves combining or mixing the therapeutic agent with the polymeric carrier to form a mixture. The mixture may then be extruded or compressed to form a single composition. The single composition may then be processed to form individual implants or microparticles suitable for placement in an eye of a patient. Solid implants suitable for use in our invention can be formed from polymer-drug blends by such methods as thermal extrusion, solvent casting, or direct compression. Our invention requires a molecular mixture of polymer and a release modifier such as fatty alcohol. Hence a compression method for making an implant is useful only if heat is applied to melt the polymeric matrix.” (page 6, column 5, lines 27-39), Example 4 wherein the freeze-dried therapeutic agent, PEG and polymer blended powder was heated to about 77° C then processed into thin filaments using a piston extruder fitted with a 500 μm exit nozzle (page 15, column 24, lines 25-64), and the hot melting extrusion step (d) of the instant claim (page 13, column 19, lines 27-51).
In addition to the teachings disclosed by Trodgen, Arrighi teaches emulsified microparticle preparation of IgG solubilized in an aqueous buffered solution composed of L-histidine, trehalose (2.1% w/v) and poloxamer 407 [central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol] (0.5% w/v) by homogenously dispersion in PLGA polymers or blends of PLGA polymers (2.5% w/v in ethyl acetate [2.7% w/w]) followed by spray-drying to achieve a theoretical IgG loading was set at 23.0 ± 0.2% (w/w) (page 2, section 2.2.1. Production of IgG-loaded PLGA microparticles). Thus, the instant claim is obvious in view of Trogden and more so in view of Arrighi.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to add the more explicitly described steps of Arrighi to the more generally described steps and invention of Trogden with a reasonable expectation of success. One would be motivated to use the explicit step described Arrighi because they were known for the same purpose and use as the more general steps disclosed by Trogden.
Claim 35 is rejected under 35 U.S.C. § 103 as being obvious over Trogden (US8318169B2; published 27 November 2012) in view of Schneider (US20190358166A1; published 20 May 2019) and in further view of Carlier (Carlier E, Marquette S, Peerboom C, Denis L, Benali S, Raquez JM, Amighi K, Goole J. Investigation of the parameters used in fused deposition modeling of poly(lactic acid) to optimize 3D printing sessions. Int J Pharm. 2019 Jun 30;565:367-377; electronically published 06 May 2019).
Regarding instant claim 35, Trogden teaches, “Additionally, drug delivery system can be made by heat extrusion, cold press, solvent casting, melt casting, solvent evaporation and other known procedures.” (page 7, column 7, lines 27-29), wherein 3D printing was a known procedure at the time of the instant invention. Trogden does not explicitly teach the specific aspects of 3D printing of instant claim 35.
Schneider explicitly teaches, macromolecular drug [which includes antibodies] blended with a polymer to form a composition that may be in the form filaments, etc., which may be shaped into the core using a variety of known shaping techniques, including fused deposition modeling three-dimensional with loading into the print head of a printer and deposition in a layer-by-layer manner positioned adjacent to an outer surface of a core [0042]-[0044]. Specifically, Schneider teaches, “The polymer composition may be supplied to the resin flow path using a variety of techniques. For example, the composition may be supplied (e.g., in the form of pellets [or filaments]) to a feed hopper attached to an extruder barrel that contains a rotating screw (not shown). As the screw rotates, the pellets are moved forward and undergo pressure and friction, which generates heat to melt the pellets. A cooling mechanism may also be provided to solidify the resin into the desired shape of the core (e.g., disc, rod, etc.) within the mold cavity. For instance, the mold bases may include one or more cooling lines through which a cooling medium flows to impart the desired mold temperature to the surface of the mold bases for solidifying the molten material.” Thus, describing a process comparable to that of instant claim to produce an equivalent outcome, wherein the filament is heated to an appropriate temperature to allow for homogenous flow during loading and deposition onto a lower temperature build platform to allow the polymeric matrix to solidify.
In addition, Carlier teaches printing implantable devices using 3D printing fused deposition modeling (FDM) technology to print filaments composed of PLA and 10% (w/w) plasticizer PEG 400 (page 1, Abstract). The deposition temperature of the printing process was within the range 155 °C to 190 °C (page 3, section 2.2.4. Experimental design and Table 2), which was above the glass transition temperature of the polymeric material of matrix (listed as Tg of 34 °C for PLA-PEG400 in Table 3, page 4). The use of the printer nozzle at the deposition temperatures is described (page 4, section 3.2. MFI analysis of the filaments) and states, “the plasticized thermoplastic polymer flowed properly through the nozzle of the printer and adhered to the build platform, regardless of the plasticizer used” which was deposited in layers (page 6, section 3.3. Manufacture of the devices by FDM). The build platform temperature was not specified and is assumed to be room temperature (approximately 20-25 °C), which would be below the specified a temperature below the glass transition temperature of the polymeric matrix.
Carlier also states, “The deposition temperature has influenced the adhesion between two successive layers and the bond quality. Distortions and defects may appear due to the rapid cooling of the matter. During deposition, the temperature of the bottom layer increases to above the Tg of the thermoplastic polymer, with a fast decrease in the temperature following the displacement of the print head.” (page 2, section 1. Introduction). Thus, it would be obvious to heat the build layer to above room temperature but below the glass transition temperature of the polymeric matrix to prevent distortions and defects caused by rapid cooling while ensuring that deposited layers adhere sufficiently, as a matter of routine experimental optimization.
As such, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to add the more explicitly described steps of Schneider and Carlier to the more generally described invention of Trogden with a reasonable expectation of success and heat the build layer to just below the glass transition temperature of the polymeric matrix to avoid deformities caused by rapid cooling on the platform described by Carlier. One would be motivated to combine these steps and make optimization improvements upon them to achieve optimum printability (e.g., avoid nozzle clogging), layer adhesion, antibody stability, device performance, and maintain desired device shape by leveraging 3D printing and polymer thermal properties.
New Rejections
The following new rejections are made from the previous Office Correspondence dated 07 August 2025, as the Applicant's amendment necessitated the new grounds of rejection presented below based on the amended/newly cited limitations.
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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 18 and 36-39 are rejected under 35 U.S.C. § 103 as being obvious over Trogden (US8318169B2; published 27 November 2012) in view of Vollrath (Vollrath M, Engert J, Winter G. Long-term release and stability of pharmaceutical proteins delivered from solid lipid implants. Eur J Pharm Biopharm. 2017 Aug;117:244-255; published electronically 22 April 2017) and in further view of Arrighi (Arrighi A, Marquette S, Peerboom C, Denis L, Goole J, Amighi K. Development of PLGA microparticles with high immunoglobulin G-loaded levels and sustained-release properties obtained by spray-drying a water-in-oil emulsion. Int J Pharm. 2019 Jul 20;566:291-298; published electronically 28 May 2019).
Trogden teaches the limitations of instant claim 18 (as described above), from which instant claims 36-39 depend, however this claim is included in the rejection on the basis of rejecting dependent claims 36-39.
The newly added limitations of claims 36-39, merely provide a specific, narrower embodiment within the scope of the prior art. The weight percentages of instant claim 36 fall within the overlapping ranges taught by Trogden, described above for claim 18. The specific combination of about 15.5% antibody, 7.5% histidine/sucrose (or trehalose) excipient, 69.5% PLGA, and 7.5% PEG is an obvious optimization of the Trogden and Vollrath teachings. Trogden teaches ranges that encompass these values (e.g., 10-20% antibody, 5-15% release modifier). Regarding Vollrath teaches the specific combination of histidine buffer with trehalose for antibody stabilization, as discussed previously. Histidine, trehalose, sucrose, PEG, and leucine are explicitly taught in Vollrath and Arrighi, as described above, and selecting specific non-critical numerical values from within the disclosed known ranges to achieve a formulation that one of skill would expect to be stable is a matter of routine result-effective optimization (see In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012), wherein optimization of process variables within known ranges is obvious). The addition of L-leucine in instant claim 37 is similarly an obvious variant, as amino acids like leucine are known in the art as bulking agents and stabilizers in spray-dried and freeze-dried protein formulations. Accordingly, instant claims 36-39 are rejected as obvious over Trogden in view of Vollrath and further in view of Arrighi.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 23 December 2025, have been fully considered.
Regarding the 35 U.S.C. § 102 rejection of claims 18, 20, 22, 26, and 28-32, the applicant’s arguments have been fully considered but are not persuasive. As explained in the prior Office Action, Trogden teaches thermoplastic polymers including PLGA (claims 1-6; Example 4); PEG plasticizers (Example 4); antibodies as therapeutic agents (column 12, lines 60-67); that the implants can be monolithic, with the active agent homogeneously distributed through the polymeric matrix (column 16, lines 43-47); a ratio of therapeutic agent (10-20% w/w) to release modifier (5-10% w/w), which yields a therapeutic agent:release modifier ratio of from 1:1 to 4:1, encompassing the claimed range of 1:1 to 5:1 (column 22, lines 6-10); a drug delivery system comprising one or more layers (column 17, lines 24-26); teaches a layer thickness of about 0.1-1.0 mm (100-1000 μm), encompassing the claimed 100 pm to 400 pm range (column 17, lines 43-44); that the systems can be of any geometry, which inherently includes those with internal hollow cavities (column 17, line 36) and geometries that include fully solid objects; and that the systems can be made by techniques including extrusion and molding. The claim is drawn to the product-by-process "obtained by 3D printing" (column 7, lines 27-29 and column 19, lines 27-34). 3D printing is merely one conventional method of shaping a filament into an object. As the product itself is not structurally different from the implants disclosed by Trogden, and 3D printing was a known procedure for shaping such materials, the claim is anticipated. The fact that Trogden does not explicitly state "3D printing" does not render it novel, as the process is not a structural limitation of the product. Therefore, as Trogden discloses each and every element of the claimed invention.
More specifically regarding claim 18, Trogden (Example 4) teaches a filament comprising a PLGA polymeric material (85% w/w), an antibody (therapeutic agent), polyethylene glycol (PEG-3350) as a plasticizer (5% w/w), and a release modifier that functions as a stabilizer (e.g., 1-hexadecanol, a surfactant/emulsion stabilizer). While the specific antibody and disaccharide/polyol stabilizer combination of claim 18 is not explicitly labeled as such, Trogden’s generic disclosure encompasses these species. Trogden (column 12, lines 60-67) explicitly lists antibodies as a therapeutic agent. Furthermore, Trogden (column 14, lines 24-29) teaches a release modifier (which can be a stabilizer as disclosed in U.S. Pat. No. 5,869,079) at 5-15% w/w. U.S. Pat. No. 5,869,079 column 3, lines 7-16, explicitly defines sugars (disaccharides like sucrose) and polysaccharides as accelerators/release modifiers. Therefore, Trogden, by incorporating the teachings of U.S. Pat. No. 5,869,079, inherently discloses a filament where the excipient (i.e., release modifier/stabilizer) can be a disaccharide or polysaccharide within the claimed 5-15% w/w range. The combination of a PLGA matrix, PEG, an antibody, and a sugar-based stabilizer, as taught by U.S. Pat. No. 5,869,079, fully anticipates the composition of claim 18. The fact that Trogden exemplifies fatty alcohols does not negate that its broad disclosure, read in light of its incorporated references, fully describes the claimed combination.
The applicant has not identified any structural or compositional limitation of claims 18, 20, 22, 26, or 28-32 that is not expressly or inherently disclosed by Trogden, therefore the § 102(a)(1) rejection of claims 18, 20, 22, 26, and 28-32 is maintained.
Regarding the rejection of claims 18 and 25 under 35 U.S.C. § 103 as being obvious over Trogden in view of Vollrath, the applicant argues that Vollrath relates to solid lipid implants and therefore would not be consulted. This argument is unpersuasive. Vollrath is cited not for polymer selection, but for well-established antibody stabilization strategies of antibodies during formulation and release using trehalose, sucrose, histidine, and hydroxypropyl-β-cyclodextrin. Vollrath explicitly teaches the use of α-trehalose, a disaccharide, and hydroxypropyl-β-cyclodextrin, a cyclic oligosaccharide, as stabilizing excipients for a monoclonal antibody in a sustained-release implant context.
Trogden, teaches the core invention including a polymeric filament (e.g., PLGA) comprising an antibody, a plasticizer (PEG), and a release modifier/stabilizer. The key limitation not explicitly exemplified in Trogden is the specific recitation of the stabilizer as a disaccharide, cyclic oligosaccharide, etc., as now recited in claims 18 and 25. Trogden expressly incorporates excipients and stabilizers from US 5,869,079, as reasoned above, including the use of disaccharide sugar (i.e., sucrose) and polysaccharides as release modifiers/stabilizers. The substitution of one known stabilizer for another known stabilizer to preserve antibody stability during thermal processing constitutes routine formulation optimization.
The motivation to combine is compelling, a person of ordinary skill in the art, seeking to formulate a stable antibody-loaded polymeric filament as taught by Trogden, would look to the art of antibody formulation for guidance on suitable stabilizers. Vollrath provides that exact guidance, demonstrating that trehalose and HP-β-CD are effective stabilizers for antibodies in a controlled-release implant. The combination is merely the application of a known technique (i.e., using sugar-based stabilizers for antibodies) to a known device (i.e., a polymeric filament) to achieve a predictable result (i.e., improved antibody stability). This is a classic case of obviousness through the combination of prior art elements according to known methods to yield predictable results (see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007)).
The applicant’s argument regarding "hindsight reconstruction" is unavailing. The reasoning provided is not based on Applicant's disclosure but on the explicit teachings of the prior art. Trogden provides the polymeric matrix and the concept of a stabilizer/release modifier, and Vollrath provides the specific, proven examples of such stabilizers for antibodies. One of ordinary skill would have been motivated to substitute the fatty alcohols of Trogden’s examples with the superior antibody stabilizers taught by Vollrath, with a reasonable expectation of success. This motivation is not hindsight, it is the logical progression of formulation science, therefore, the § 103 rejection of claims 18 and 25 over Trogden in view of Vollrath is maintained.
Regarding the 35 U.S.C. § 103 of claims 18 and 33, the applicant argues that Schneider does not remedy alleged defects in Trogden. This argument is not persuasive. Trogden teaches the filament and broadly discloses its formation into implants via techniques like extrusion and molding. Schneider provides the explicit motivation to use a specific, well-known shaping technique of 3D printing. Schneider teaches the use of filaments comprising a polymer and a macromolecular drug (e.g., an antibody) in a fused deposition modeling (FDM) 3D printing process to create implantable devices. The process described in Schneider of loading a filament into a print head, heating it, and depositing it layer-by-layer, is directly analogous to the process now claimed in claim 35.
The combination of Trogden’s filament with Schneider’s teaching of 3D printing that filament would have been obvious. The combination merely substitutes one known shaping technique for another, yielding predictable results. One of ordinary skill, having a filament as taught by Trogden, would look to Schneider for a method to shape that filament into a patient-specific or complex implant, which is the precise purpose of 3D printing in this field. The § 103 rejection of claims 18 and 33 is maintained.
Regarding the rejection of claim 34 under 35 U.S.C. § 103 as being obvious over Trogden in view of Arrighi, the applicant argues that Arrighi does not cure deficiencies in Trogden, but as established above, Trogden is not defective, wherein it provides the foundational structure. This argument is not persuasive. Trogden teaches freeze-dried therapeutic agents blended with polymer and extruded. While Vollrath teaches the stabilizers, Arrighi teaches a complementary process for forming high-loaded antibody microparticles suitable for incorporation into a PLGA matrix. Arrighi teaches a process of preparing antibody-loaded PLGA microparticles by spray-drying an emulsion containing the antibody, L-histidine, trehalose, and poloxamer. This directly teaches the specific excipient combination of histidine and trehalose/sucrose now claimed and loading levels.
The motivation to combine Trogden’s filament manufacturing process (HME of a blend) with Arrighi’s microparticle preparation method is clear, to create a homogeneous dispersion of stabilized antibody particles within the polymer matrix, a technique expressly claimed by the applicant in claim 34 and resulting in the filaments of claims 36-39. One of ordinary skill would have been motivated to adopt Arrighi's method to improve the stability and loading of the antibody in Trogden's filament. Combining Arrighi’s explicit process steps with Trogden’s extrusion process would have been obvious with a reasonable expectation of success. The § 103 rejection of claim 34 is maintained.
Regarding the rejection of claim 35 under 35 U.S.C. § 103 as being obvious over Trogden in view of Schneider and in further view of Carlier, the applicant’s arguments regarding motivation and expectation of success are not persuasive. The applicant argues that Carlier fails to remedy the defects of Trogden. However, this rejection addresses the specific sub-step of claim 35 not explicitly detailed in Schneider of heating the build platform to a temperature below the glass transition temperature (Tg) of the polymeric material.
Trogden and Schneider provide the basis for the filament and the 3D printing process. Schneider teaches FDM-style filament loading, heating, and layer-by-layer deposition. Carlier provides the specific process optimization. Carlier teaches FDM 3D printing of a PLA/PEG filaments, extrusion temperatures above Tg, and deposition onto a cooler build platform. Critically, Carlier discusses the importance of thermal control during printing, noting that the temperature of the deposited layer increases above Tg and then rapidly cools, which can cause distortions. Heating the platform to below Tg represents routine optimization to improve adhesion and prevent warping. The reference teaches that the build platform, while not specified, is generally at room temperature (approx. 20-25°C), which is below the Tg of PLA-PEG (listed as 34°C).
The logical optimization to prevent the "distortions and defects" mentioned by Carlier would be to actively control the build platform temperature to be just below the Tg, high enough to promote layer adhesion and prevent warping from rapid cooling, but low enough to maintain the part's shape. This is a routine optimization of process parameters to achieve the well-known goal of improving print quality and layer adhesion, as evidenced by Carlier's discussion. Therefore, the specific limitation of heating the build platform to a temperature below the Tg would have been obvious to a skilled artisan seeking to optimize the 3D printing process taught by Schneider and Carlier. The applicant has not provided evidence of unexpected results or criticality, therefore, the § 103 rejection of claim 35 is maintained.
Newly added claims 36-39 recite narrowed compositional percentages and specific excipient combinations. These limitations do not confer patentability, because the recited weight percentages fall within the overlapping ranges taught by Trogden, histidine, trehalose, sucrose, PEG, and leucine are explicitly taught in Vollrath and Arrighi, and selecting specific numerical values within known ranges is result-effective optimization. Accordingly, claims 36-39 are rejected under 35 U.S.C. § 103 as obvious over Trogden in view of Vollrath and further in view of Arrighi.
In summary, the prior art of record, particularly Trogden in view of Vollrath, Arrighi, Schneider, and Carlier, teaches or suggests all the limitations of the pending claims. The claimed invention is an obvious combination of well-known elements: a polymeric filament (Trogden), antibody stabilizers (Vollrath), a method for incorporating antibodies into polymers (Arrighi), a 3D printing method (Schneider), and optimization of 3D printing parameters (Carlier). The motivation to combine these references is found in the desire to create a stable, 3D-printed, implantable antibody delivery device, a goal explicitly shared by the prior art. The applicant’s arguments do not rebut the prima facie case of obviousness. No persuasive evidence of unexpected results, teaching away, or criticality has been provided. The pending claims remain anticipated or obvious over the cited art.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new 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 (87 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.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615