DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/20/2026 has been entered.
Response to Amendment
Applicant’s response of 07/20/2026 has been received and entered into the application file. Claims 1, 6, 12-18, 21, 23-25, 28-29, 31-33, 35-36, 38-40, 42-44, 47-48 and 68-72 are pending in this application. New claims 68-72 are added.
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.
Elected Species
In the reply to restriction and election of species requirements of 08/26/2025, the applicants have elected peptide as the species of active pharmaceutical ingredient. Any and all semi-solid injectable formulations containing any peptide will read on claim 1.
Claims 1, 6, 12-18, 21, 23-25, 28-29, 31-33, 35-36, 38-40, 42-44, 47-48 and 68-72 are rejected under 35 U.S.C. 103 as being unpatentable over Donovan (US 2017/0216529 A1) Shen et al. (US 2005/0042194 A1) and Chen et al. (WO 2020/106948 A1).
Donovan discloses a syringe body defining a reservoir having an internal first transverse dimension, a paste disposed within the reservoir, the paste having a solids concentration of greater than 50 mg/mL, the needle configured to be in fluid communication with the reservoir to allow intracutaneous delivery of the paste, and a plunger and/or piston disposed within the reservoir and configured to be moved to dispense paste from the reservoir through the lumen (Abstract). In some embodiments of the present pre-loaded syringes, the paste has a volume of between 15, 50, 100, or 500 μL and 1000, 2000, or 3000 μL ([0017]). Some embodiments of the present pre-loaded syringes are configured to dispense paste at a flow rate of at least about, about, or greater than 15 microliters per second (μL/s) ([0018]). In some embodiments of the present syringes, kits, and/or methods, the paste has a solids concentration of greater than 200 mg/mL. In some embodiments, the paste has a solids concentration of between 200 and 600 mg/mL ([0026]). For further example, paste can comprise a solids content (e.g., a mass of powder relative to a total mass of the paste) of between 30% and 40% (e.g., 35%) (e.g., greater than any one of, or between any two of 1,5, 10, 15,20,25,30,35,40,45,50, 55,60,65, 70, 75,80, 85, 90, 95, 99 or more%) ([0077]). A spray dried powder containing a monoclonal antibody (where the dried powder contained approximately 70% (w/w) protein) was used to prepare a high-concentration paste formulation by blending the powder with Miglyol 812 ([0095]). Donovan discloses that the composition comprises a pharmaceutically acceptable carrier such as a solvent, suspending agent or vehicle for delivering a compound of the present invention to the animal or human ([0041]). Donovan discloses that the term “controlled-release” is defined as the release of the therapeutic agent such a rate that blood concentrations are maintained within the therapeutic range but below toxic concentrations over a period of time of about one hour or longer, preferably 12 hours or longer ([0050]). One of ordinary skill in the art would immediately envisage that the therapeutic level of one or more active ingredients would be sustained for over 12 hours or longer, including at least one week.
Shen discloses a semi-solid delivery vehicle comprising a polyorthoester and an excipient (Abstract). Active agent includes pharmaceutically active agents which may be administered via injection such as subcutaneous, intramuscular, intradermal; therapeutic polypeptides such as insulin ([0046]). Shen teaches that “semi-solid” denotes the mechano-physical state of a material that is flowable under moderate stress. More specifically, semi-solid material should have a viscosity of between about 10,00 and 3,000,000 cps ([0056]). One of ordinary skill in the art would immediately envisage that a semi-solid material would have a viscosity above about 50 cP.
Chen discloses compositions and methods of making high concentration protein formulations of a therapeutic protein (Abstract). The present invention satisfies the need for high concentration protein formulation comprising at least 200 mg/mL of a therapeutic protein ([0006]). the excipients in the high concentration protein formulation may include (i) a carbohydrate; (ii) an amino acid; and (iii) a non-ionic surfactant. The carbohydrate may be selected from sucrose, mannitol, sorbitol, dextran, maltodextrin, trehalose, or combinations thereof. The amino acid may be selected from proline, histidine, isoleucine, methionine, cysteine, glycine, arginine, lysine, L-leucine, Tri-leucine, alanine, glutamic acid, aspartic acid, L-threonine, 2-phenylamine, or combinations thereof. The non-ionic surfactant may be selected from polysorbate 20 (PS-20), polysorbate 28, polysorbate 40 (PS-40), polysorbate 65, polysorbate 80 (PS-80), polysorbate 81, polysorbate 85, poloxamer 181 ([0009]). As used herein, "therapeutic protein" includes any of proteins, recombinant proteins used in research or therapy, trap proteins and other chimeric receptor Fe-fusion proteins, chimeric proteins, antibodies, monoclonal antibodies, polyclonal antibodies, human antibodies, and bi specific antibodies. In another aspect, a protein can include antibody fragments, nanobodies, recombinant antibody chimeras, cytokines, chemokines, peptide hormones ([0066]). The formulation further includes buffering agents ([0076]).
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 paste having a solid concentration of greater than about 350 mg/mL. 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 6, solids concentration and a relative content of active pharmaceutical ingredient are discussed above.
Regrading claims 12-14, a peptide or protein therapeutic is discussed above.
Regarding claims 15-18 and 21, Donovan and Shen both disclose an injectable paste containing peptide or protein. One of ordinary skill in the art would immediately envisage experimenting with other pharmaceutically active agents such as different peptides and proteins.
Regarding claims 23-25, insulin is discussed above.
Regarding claims 28-29, as discussed above, one of ordinary skill in the art would experiment with different peptides or proteins via routine experimentation.
Regarding claims 31-32, monoclonal antibody is taught above.
Regarding claim 33, one of ordinary skill in the art would experiment with different peptides or proteins via routine experimentation.
Regarding claim 35, Chen teaches that the formulation is useful for the treatment and/or amelioration of a disease or disorder such as cancer ([0094]). One of ordinary skill in the art would immediately envisage experimenting with an anticancer agent.
Regarding claim 36, one of ordinary skill in the art would experiment with different peptides or proteins via routine experimentation.
Regarding claims 38-40, Chen discloses many therapeutic uses of the pharmaceutical formulations such as cancer, neurocognitive disorder, obesity, tuberculosis, and others ([0094]). One of ordinary skill in the art would routinely experiment with agents helpful for many different diseases and/or disorders.
Regarding claims 40-44, Chen discloses excipients as discussed above.
Regarding claims 47-48, Chen discloses excipients as discussed above.
Regarding claim 68, Chen discloses that spray drying is a technique that transforms a fluid state into a dried particulate form by spraying it into a hot drying medium. This micronized solid protein formulation can comprise a carbohydrate, an amino acid and a surfactant such as polysorbate ([0070]).
Regarding claim 69, Donovan discloses that a spray dried powder containing a monoclonal antibody was turned into a paste with Miglyol or capric triglyceride ([0095]).
Regarding claims 70-71, Donovan discloses that semi-solids such as gels in which the macromolecules are distributed are considered colloidal dispersion; the generally accepted size range for a substance “colloidal” is when particles fall between 1 nm and 0.5 micrometer ([0036]). One of ordinary skill in the art would recognize that semi-solids such as gels or paste could have ingredients with a mean particle size from 1 nm to 0.5 micrometer.
Regarding claim 72, Donovan discloses that the measured density of the paste was 1.12 g/mL ([0095]).
Response to Arguments
Applicant’s arguments filed 07/20/2026 have been fully considered but they are not persuasive.
On pages 13 of remarks, Applicant argues that there would have been no reason to modify the formulations in the cited art. Per MPEP 2145 (IV), One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Every cited art is in the field of high-concentration protein formulations, perfectly relevant to the instant application. Applicant argues that Chen reference includes a viscosity-reducing agent. Chen discloses that for subcutaneous administration, viscosity and protein stability can be primary limitations for viable high concentration protein formulations ([0046]). Chen simply teaches that viscosity is an important parameter to consider when formulating a high-protein concentration. Likewise, one of ordinary skill in the art would carefully consider and optimize viscosity for a high-concentration protein formulation that needs to be injected through a syringe. On page 14 of remarks, Applicant argues that Chen’s formulation is a suspension. However, Chen discloses that suspensions can be made into more viscous pate-like suspension ([0106]). One of ordinary skill in the art would recognize that a suspension can be turned into a semi-solid paste when mixed with different pharmaceutical vehicles.
On page 15 of remarks, Applicant argues that there would be no reasonable expectation of success in achieving a composition with the pharmacokinetic parameters recited in claim 1. In turn, the Examiner cannot determine how the instant application’s invention achieves the pharmacokinetic parameters as recited in claim 1. Claim 1 is a general claim of a paste having a certain solid concentration, one or more active pharmaceutical ingredients, one or more excipients, one or more non-solvent fluids, with pharmacokinetic parameters that are predictable to one of ordinary skill in the art. Claim 1 does not include any specific element that separates from teachings of prior art references. Is it a specific peptide? Is it a specific saccharide, surfactant or an amino acid within the formulation? Is it a certain combination of ingredients that impart these parameters? A high-protein concentration would be expected to have a therapeutic level of whatever is injected to be sustained over a longer period of time when compared to a lower-protein concentration product. The definition of “sustained-release” is already discussed above by Donovan.
The “dramatic expansion and improvement” of a paste formulation over Donovan cannot be determined by the Examiner as currently written in claim 1.
Conclusion
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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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