DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
Applicant’s response of 08/10/2026 has been received and entered into the application file. Claims 1-45 are pending in this application.
Applicant’s amendments to the Specification and claims have overcome 112(a) and 112(b) rejection previously set forth in the Non-Final Office Action mailed 04/10/2026.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-13, and 15-37 are rejected under 35 U.S.C. 103 as being unpatentable over Roberge et al. (WO 2019/016234 A1), Park et al. (US 2016/0051469 A1), Boyd et al. (US 2008/0214995 A1), further evidenced by Banado et al. (US 2018/0016333 A1).
Roberge discloses a biodegradable drug delivery composition comprising a mixture of at least two block copolymers taken among triblock and diblock copolymers comprising: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax wherein A is a polyester and B is polyethylene glycol and v and x are from I to 3,000 and w is from 3 to 300 and v=x or v does not equal x; (b) a biodegradable di block copolymer having the formula: Cy-Az wherein A is a polyester and C is an end-capped polyethylene glycol and y and z are the number of repeat units with y =2 to 250 and z =1 to 3,000; wherein the weight ratio between (a) and (b) is 1:19 to 5:1; and for at least one of the copolymers according to (a) or (b) A is poly(e-caprolactone-co-lactide); and (c) at least one pharmaceutically active ingredient. Roberge discloses that peptide or protein drugs can be entrapped in the composition (pg 27, lines 25-28). The triblock can be present in an amount of 1% to 50% (w/w%) and the diblock copolymer can be present in an amount of 1% to 57% (w/w%) (pages 26-27). The active ingredient can be present in an amount of 0.05% to 60% (w/w%) (pg 29). Organic solvent used in the preparation can be in an amount of 25% to 90% (w/w%) (pg 33).
Roberge does not explicitly mention interleukin-1 antagonist.
Park discloses therapeutic delivery systems which includes a thermally-sensitive copolymer and a therapeutic agent (Abstract). The compositions and systems are configured to provide sustained release of the therapeutic agent ([0006]). The system includes a reverse thermal gel (RTG), which is an aqueous polymer that reversibly transitions from a liquid to a physical gel. The system can include polymeric systems such as AB diblock, ABA triblock and/or graft copolymer. A is a hydrophilic polymer and B is a hydrophobic polymer ([0007]). The system can include one or more therapeutic agents such as interleukin-1 antagonist agent, canakinumab ([0070]).
Above references do not explicitly mention stabilizers.
Boyd discloses formulations that are viscous (Abstract). The formulation is capable of forming a depot ([0099]). One of the formulations contemplated is thermoreversible hydrogels including poloxamers, diblock copolymers, triblock copolymers ([0110]). Boyd discloses that a stabilizer such as sucrose is routinely used in delivery systems ([0013]).
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to create a composition comprising a triblock copolymer, diblock copolymer, and a therapeutic protein formulated as a long-lasting injection. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claims 2-3, Roberge discloses the range of integers. Per MPEP 2144.05 (I), "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." Roberge discloses that the polyester repeat unit to ethylene oxide molar ratio is between 0.5 to 22.3 (pg 7, lines 32-34). Roberge discloses that the method is valid for molecular weight of PEGs above 1000 g/mol (Dalton) (pg 41, lines 13-14).
Regarding claims 4-5, Roberge discloses that the polyester to ethylene oxide molar ratio is 0.8 to 15 for the diblock copolymer (pg 26, line 10). The weight of the end-capped polyethylene glycol can range from 120 g/mol to 10,000 g/mol (pg 26, lines 17-18). Per MPEP 2144.05 (I), "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness."
Regarding claims 6-7, Roberge teaches that when the polyester in the triblock is not PCLA, the polyester in the triblock can 25 be polylactic acid (PLA), polycaprolactone (PCL), polyethylene adipate (PEA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid (PLGA) polyhydroxyalkanoate (PHA) or mixtures thereof (pg 21, lines 24-27); And when the polyester in the diblock is not PCLA, the polyester in the diblock can be polylactic acid (PLA), polycaprolactone (PCL), polyethylene adipate (PEA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA) or polyhydroxyalkanoate 20 (PHA) or mixtures thereof (pg 22, lines 17-20).
Regarding claims 8-9, polyester A is discussed above.
Regarding claim 10, Roberge uses 75G PEG-PLGA or PLGA-PEG-PLGA; the term 75G refers to PLGA polyester based block copolymer, 75 being the LA/GA molar ratio (pg 17, line 16).
Regarding claim 11, the composition comprises a therapeutic protein IL-1Ra. Interleukin antagonist is discussed above.
Regarding claim 12, canakinumab is discussed above.
Regarding claim 13, one of ordinary skill in the art would contemplate any and all therapeutic proteins within a depot-injection composition as taught by Roberge above. Canakinumab and rilonacept both share the same mechanism of action.
Regarding claim 15, canakinumab’s molecular weight falls within the claimed range.
Regarding claim 16, Active ingredient w/w % is discussed above.
Regarding claim 17, organic solvent is discussed above.
Regarding claims 18-19, Roberge discloses that the composition may comprise an organic solvent. The 5 organic solvent may be selected from the group of: benzyl alcohol, benzyl benzoate, dimethyl isosorbide (DMI), dimethyl sulfoxide (DMSO), ethyl acetate, ethyl benzoate, ethyl lactate, glycerol formal, methyl ethyl ketone, methyl isobutyl ketone, N-ethyl-2- pyrrolidone, N-methyl-2-pyrrolidinone(NMP), pyrrolidone-2, tetraglycol, triacetin, tributyrin, tripropionin (tripro), and mixtures thereof. In one embodiment DMSO, 10 NMP, tripro or mixtures thereof can be used as solvents (pg 31, lines 4-10).
Regarding claims 20-21, Roberge discloses that the composition can further comprise pharmaceutically acceptable carrier, adjuvant, or vehicle (pg 30). One of ordinary skill in the art would contemplate an adjuvant such as a stabilizer to maintain the stability of the composition before it is injected into a patient. As discussed above, sucrose can be used as a stabilizer and any and all stabilizers routinely used in the art would be equally contemplated. Banado further evidences this by disclosing that the aqueous stable antibody composition includes stabilizers (Abstract); stabilizers can include mannitol, trehalose, sorbitol, sucrose ([0006]).
Regarding claims 22-23, w/w % of copolymers is discussed above.
Regarding claim 24, one of ordinary skill in the art would routinely experiment with different weight ratios of copolymer within a polymeric blend to control drug release profile and characteristic. Roberge teaches that the copolymers are present in an amount of 2-60% (w/w%) of the total composition (pg 34, line 29).
Regarding claim 25, Roberge discloses buffered saline as an acceptable carrier (pg 30, line 19) such as phosphate-buffered saline (pg 53).
Regarding claim 26, Roberge discloses that the active ingredient means a drug or medicine for treating or preventing various medical illnesses (pg 15, line 18).
Regarding claims 27-28, one of ordinary skill in the art would recognize that an active ingredient meant to treat rheumatic disease can be included in a pharmaceutical composition to treat those particular diseases. Canakinumab discussed above would treat rheumatic diseases.
Regarding claim 29, Roberge discloses that the composition can be administered via intra-articular route (pg 20, line 5).
Regarding claim 30, one of ordinary skill in the art would routinely inject a pharmaceutical composition intended to treat arthritis into the vicinity of a synovial joint.
Regarding claim 31, depot injection is discussed in Roberge (pg 24, line 27).
Regarding claim 32, rheumatic disease is discussed above.
Regarding claim 33, Wang discloses that single domain antibody inhibited synovitis and cartilage/bone erosion (Conclusion section). Likewise, one of ordinary skill in the art would expect an anti-rheumatic agent within a pharmaceutical composition would have an effect on rhematic diseases.
Regarding claims 34-35, intra-articular injection is discussed above.
Regarding claim 36, Roberge discloses 23G needle was used to inject the compositions (pg 48).
Regarding claim 37, Roberge discloses that the composition should enable the release of the at least one active ingredient to be controlled over a time period without adversely affecting the physical parameters of the formulation (pg 2, lines 23-25). Furthermore, Roberge discloses that the composition’s depot release profile can be modulated (pg 18, line 26). One of ordinary skill in the art would immediately envisage that a composition comprising a triblock and a diblock copolymers would inherently have this characteristic. It would not be surprising to discover that a concentration of the active ingredient within the injection site would be higher than a serum concentration.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Roberge et al. (WO 2019/016234 A1), Park et al. (US 2016/0051469 A1), and Boyd et al. (US 2008/0214995 A1) as applied to claims 1-13 and 15-37 above, and further in view of Wang et al. (Inhibition of synovitis and joint destruction by a new single domain antibody specific for cyclophilin A in two different mouse models of rheumatoid arthritis, Arthritis Research & Therapy, 2013).
Wang discloses that cyclophilin A (CypA) is implicated in rheumatoid arthritis (RA) pathogenesis. A novel single domain antibody treatment significantly inhibited synovitis and cartilage/bone erosion. Finding provide evidence that single domain antibody may be a potential therapeutic agent for RA (Abstract).
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined a depot injection targeting rheumatoid arthritis to include a single domain antibody. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claims 38-45 are rejected under 35 U.S.C. 103 as being unpatentable over Roberge et al. (WO 2019/016234 A1), Park et al. (US 2016/0051469 A1), and Boyd et al. (US 2008/0214995 A1) as applied to claims 1-13 and 15-37 above, and further in view of Ibeanu et al. (Injectables and Depots to Prolong Drug Action of Proteins and Peptides, pharmaceutics, 2020) and Schmidt et al. (Stabilizing Polysorbate 20 and 80 Against Oxidative Degradation, J Pharm Sci. 2020).
Roberge discloses that the copolymers were dissolved in DMSO. Then the drug was added to the copolymer solution (pg 41). Roberge teaches mixing the copolymer solution with an active ingredient. Roberge does not explicitly teach spray drying a therapeutic protein solution.
Ibeanu discloses that proteins and peptides have emerged to treat a wide range of diseases (Abstract). Many methods exist to fabricate particulate formulations including spray drying (pg 7). Spray drying is a well-established method; spray drying can be scaled, cost-effective, and can be optimized. Even though spray drying an aqueous solution of protein can result in loss of stability, the use of mixed aqueous-organic liquids can diminish this concern (pg 8).
Schmidt discloses that polysorbates are stabilizers required in therapeutic protein formulation (Abstract).
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined the method steps taught by Roberge with the method taught by Ibeanu. Spray drying is a well-known, already practiced method for protein/peptide formulations. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 39, copolymer w/w% is discussed above.
Regarding claim 40, therapeutic protein w/w% is discussed above.
Regarding claim 41, one of ordinary skill in the art would contemplate adding a stabilizer into a depot formulation as discussed above.
Regarding claim 42, buffer is taught above.
Regarding claim 43, phosphate buffer is taught above.
Regarding claim 44, polysorbate in a therapeutic protein formulation is discussed above.
Regarding claim 45, Park discloses that the emulsion can be passed through a filter ([0108]). Likewise, one of ordinary skill in the art would routinely filter pharmaceutical formulations.
Response to Arguments
Applicant’s arguments filed 08/10/2026 have been fully considered but they are not persuasive.
On pages 14-16 of remarks, applicant argues that the pharmaceutical composition of the present invention were found to be suitable for administration of therapeutic IL-1 antagonist to the intraarticular space through formation of depot that provides a sustained release of the therapeutic protein over a period of weeks or months and this “surprising” efficacy is evidenced by at least Examples 3 and 4 of the specification. The examiner agrees that the formulation of instant application works as intended by the applicants. Example 3 shows that IL-1Ra in the synovial fluid and joints of the knee were still measurable at least 28 days after injection. Table 5 shows that rats treated with the formulations F4 and F5 had a much-improved bearing deficit compared with the control formulations 37 days after treatment. As discussed in the non-final rejection, Roberge discloses a biodegradable drug delivery composition comprising a mixture of the triblock and diblock copolymers, the same as in instant claim 1. Roberge discloses that the depot can be administered via intraarticular route (pg 16, lines 10-12). Roberge discloses that in the domain of sustained drug delivery, systems based on diblock or triblock copolymers have been used to deliver a variety of drugs and are generally formulated to deliver specific drugs whether they are hydrophobic drugs or hydrophilic drugs (pg 1, lines 18-21). Roberge discloses that an active ingredient can be peptide/protein drugs (pg 27, lines 25-28). Roberge teaches that a sustained depot delivery by using copolymers is well-known and the active ingredient can be protein drugs. Instant application uses the same triblock/diblock copolymers and the examiner cannot determine if the unexpected efficacy/results are only possible with the claimed therapeutic protein. Claim 1 does not separate from teachings of prior art references.
On page 16 of remarks, applicant argues that Roberge does not disclose any specific IL-1 antagonist. Roberge does not have to explicitly mention as he teaches that the combination of triblock/diblock copolymers in a depot formulation is used to control release profile. Roberge discloses that an active agent can be a protein drug which would include IL-1 antagonist. Roberge discloses intraarticular administration as well.
On page 17 of remarks, applicant argues that Park has a very different chemistry to the copolymers as recited in present claim 1. Per MPEP 2145 (IV), One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Park was incorporated to teach that IL-1 antagonists are routinely used biodegradable delivery systems.
Therefore, claims remain rejected.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN SEUNGJAI KWON whose telephone number is (571)272-7737. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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