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 .
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 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.
DETAILED ACTION
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/19/2026 was filed after the mailing date of the non-final rejection on 04/01/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of claims
The amendment filed on 06/19/2026 is acknowledged. Claims 1-55 have been canceled and claims 82-87 have been withdrawn. Claims 56-81 are under examination in the instant office action.
Rejections withdrawn
Applicant’s amendments and arguments filed on 06/19/2026 are acknowledged and have been fully considered. Any rejection and/or objection not specifically addressed below is herein withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Rejections maintained
The following rejections of the claims are remained for reasons of record and the following.
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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 56-81 are rejected under 35 U.S.C. 103(a) as being unpatentable over Hunter et al. (US 2002/0119202 A1) in view of Hunter et al. (US 2002/0192280 A1).
Hunter et al. (‘202) teach a method of treating rheumatoid inflammatory arthritis (the patient population includes patient population with acute and/or patient population with chronic and includes crystal-associated patient population or non- crystal-associated patient population in the instant claims 56, 61, and 62 and includes patient population with renal and/or hepatic impairment and patient population being simultaneously, separately or sequentially treated by atazanavir, etc., in the instant claim 81) with painful joints (the instant claim 56) (paragraph 166) comprising
intra-articular injection to an involved joint (including any joint, the instant claim 64) (paragraph 163-165) of composition in form of suspension (the instant claim 56) (paragraph 194) comprising
copolymer of lactic acid and glycolic acid or poly(caprolactone) sustained release microspheres (the instant claims 56, 59, 60, 76, and 78) (paragraph 129, 147, 217, and 429) comprising colchicine (the instant claim 56) or paclitaxel (paragraph 15 and 114 and claims 1, 2, and 6-11) with size of 10-30 µm (the instant claims 56, 71, and 72) (paragraph 120 and 263); and
exemplified intra-articular injection of 0.2 mL (0.5 mg microspheres) of a composition comprising paclitaxel-containing microspheres (obvious to be replaced by colchicine) in example 19 (the instant claim 56);
wherein a drug is released 80% at 1-10 days and about 40% at 12 hours (figure 12) and copolymers of lactic acid and glycolic acids have faster degradation rates than PLA and drug loaded microspheres prepared using these copolymers, the degradation lifetime of PLA is increased as the proportion of EVA in the blend is increased (paragraph 340), i.e., the release relate of a drug is related to the choice of microsphere polymer blend (the instant claims 56 and 65-68);
wherein microspheres have 5% by weight of paclitaxel loaded (obvious to be replaced by colchicine) (the instant claims 56, 78, and 79) (paragraph 323) and
the composition comprising microspheres of both quick and slow or prolonged release of paclitaxel (obvious to be replaced by colchicine) (the instant claim 75) (paragraph 119, 219, and 521).
With 0.2 mL composition comprising 0.5 mg microspheres and paclitaxel (obvious to be replaced by colchicine) is loaded at 5% by weight of the microspheres, the concentration of paclitaxel (obvious to be replaced by colchicine) is calculated to be 125 µg/mL (0.5 mg x 5%) / 0.2 mL → 0.025 mg / 0.2 mL → 25 µg / 0.2 mL → 125 µg/mL (the instant claims 56-58).
The limitation I the instant claim 63 is further limitation of an alternative limitation.
Hunter et al. are silent about the systemic concentration and synovial concentration of colchicine after intra-articular injection of colchicine (the instant claims 69 and 70), the method (the composition and route of administration) taught by Hunter et al. are the same as the claimed, the method taught by Hunter et al. would result in the same systemic concentration and synovial concentration of colchicine after intra-articular injection of colchicine. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant’s own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise.
The limitation in the instant claim 73 is a product-by-process limitation of a product used in the claimed method. The determination of patentability of a product-by-process claim is based on the product itself, not its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process. The burden is shifted to the applicant to provide evidence to demonstrate that the structure of composition used in the claimed method resulted from the said process is different from that of composition disclosed in the prior art. See MPEP 2113.
Hunter et al. are silent about the viscosity of the composition (the instant claim 74). Since the composition in the method taught by Hunter et al. is suitable for intra-articular injection, as the composition used in the claimed method, it is reasonable to assume the composition in the method taught by Hunter et al. would have the similar viscosity as the claimed composition.
Hunter et al. do not specify the amount of composition for intra-articular injection into each specific joint in the instant claim 80.
It would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to determine the dosage for intra-articular injection into each specific joint. The person of ordinary skill in the art is a health care provider, pharmacist, or medicinal chemist. The claimed drug is already known in the art, the art also recognizes what conditions are treatable by the claimed drug, and the route of administration is known. The claimed dosage for intra-articular injection into each specific joint represents no more than a determination of the workable range or amount of drug for achieving the known effect. Determining optimum dosages is routine in the pharmaceutical arts. Thousands of different drugs are sold to the public by prescription or over the counter, and for each of them, the appropriate or optimal dosage has been determined.
Claims 56-81 are rejected under 35 U.S.C. 103(a) as being unpatentable over Hunter et al. (US 2002/0192280 A1) in view of Hunter et al. (US 2002/0119202 A1).
Hunter et al. (‘280) teach a method of (the patient population includes patient population with acute and/or patient population with chronic and includes crystal-associated patient population or non- crystal-associated patient population in the instant claims 56, 61, and 62 and includes patient population with renal and/or hepatic impairment and patient population being simultaneously, separately or sequentially treated by atazanavir, etc., in the instant claim 81) with painful joints (the instant claim 56) (paragraph 99) comprising
intra-articular injection to an involved joint (including any joint, the instant claim 64) (paragraph 99 and 103-106 and claim 104) of composition in form of suspension (the instant claim 56) (paragraph 25) comprising
anti-microtubule agent (colchicine)-containing polymeric microsphere carrier in form of dispersion (paragraph 53 and 75 and claim 105 and 112) with size of 10-30 µm (the instant claims 56, 71, and 72) (paragraph 75).
The limitation I the instant claim 63 is further limitation of an alternative limitation.
The limitation in the instant claim 73 is a product-by-process limitation of a product used in the claimed method. The determination of patentability of a product-by-process claim is based on the product itself, not its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process. The burden is shifted to the applicant to provide evidence to demonstrate that the structure of composition used in the claimed method resulted from the said process is different from that of composition disclosed in the prior art. See MPEP 2113.
Hunter et al. are silent about the viscosity of the composition (the instant claim 74). Since the composition in the method taught by Hunter et al. is suitable for intra-articular injection, as the composition used in the claimed method, it is reasonable to assume the composition in the method taught by Hunter et al. would have the similar viscosity as the claimed composition.
Hunter et al. (‘280) are silent about the viscosity of the composition (the instant claim 74). Since the composition in the method taught by Hunter et al. (‘280) is suitable for intra-articular injection, as the composition used in the claimed method, it is reasonable to assume the composition in the method taught by Hunter et al. (‘280) would have the similar viscosity as the claimed composition.
Hunter et al. (‘280) do not specify the amount of composition for intra-articular injection into each specific joint in the instant claim 80.
It would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to determine the dosage for intra-articular injection into each specific joint. The person of ordinary skill in the art is a health care provider, pharmacist, or medicinal chemist. The claimed drug is already known in the art, the art also recognizes what conditions are treatable by the claimed drug, and the route of administration is known. The claimed dosage for intra-articular injection into each specific joint represents no more than a determination of the workable range or amount of drug for achieving the known effect. Determining optimum dosages is routine in the pharmaceutical arts. Thousands of different drugs are sold to the public by prescription or over the counter, and for each of them, the appropriate or optimal dosage has been determined.
Hunter et al. (‘280) do not teach the same claimed polymer of the sustained release microspheres in the instant claims 56, 59, 60, 76, and 78, the volume of the injection in the instant claim 56, the concertation of colchicine in the instant claims 56-58, the release profile in the instant claims 56 and 65-68, the composition comprising microspheres of both quick and slow or prolonged release of colchicine in the instant claim 75, the systemic concentration and synovial concentration of colchicine after intra-articular injection of colchicine in the instant claims 69 and 70.
This deficiency is cured by Hunter et al. (‘202) whose teachings are discussed above and applied in the same manner.
It would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to combine the teachings in Hunter et al. (‘280) and Hunter et al. (‘202) to specify the polymer of the sustained release microspheres being copolymer of lactic acid and glycolic acid or poly(caprolactone) sustained release microspheres, the injection volume being 0.2 mL with 0.5 mg microspheres → 125 µg/mL anti-microtubule agent (colchicine) concertation, release 80% at 1-10 days and about 40% at 12 hours and the release relate of a drug is related to the choice of microsphere polymer blend, the composition comprising microspheres of both quick and slow or prolonged release of colchicine, the systemic concentration and synovial concentration of colchicine after intra-articular injection of colchicine. Colchicine being formulated for intra-articular injection to an involved joint for treating acute rheumatoid inflammatory arthritis as taught by Hunter et al. (‘202) was well known to a person of ordinary skill in the art before the effective filing date of the claimed invention. The motivation for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose.
Response to Applicants’ arguments:
Applicants argue that colchicine is one of the options taught by Hunter et al. (‘202).
However, this argument is not deemed persuasive. Although colchicine is listed among seven compounds; Hunter et al. (‘202) do teach in claim 11 as colchicine as one of the compounds for treating inflammatory arthritis (paragraph 22-24).
Applicants argue that Hunter et al. (‘202) teach 80% release of sodium suramin within one day in figure 12, not the claimed 80% release colchicine in more than 1 day.
However, this argument is not deemed persuasive.
First, the days of 80% release of sodium suramin in figure 12 also include day 5. Hunter et al. (‘202) also teach >25% w/v release an anti-angiogenic factor (including colchicine (paragraph 15 and 22-24)) over 7-10 days (paragraph 119) which encompasses the claimed >1 day after administration releasing 80% by weight.
Second, Hunter et al. (‘202) teach compositions for delivering anti-angiogenic factor comprising an anti-angiogenic factor and a polymeric carrier with the anti-angiogenic factor including suramin (paragraph 14) and colchicine (paragraph 15 and 22-24). Thus, Hunter et al. (‘202) teach compositions for delivering suramin or colchicine comprising suramin or colchicine and a polymeric carrier while polymeric carrier determines the release profile (paragraph 214). Thus, it would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to assume replacing suramin in the formulation having the release profile of suramin in figure 12 with colchicine would result in the same release profile of colchicine as the release profile of suramin in figure 12.
Applicants argue that paragraph 194 recited in the rejection is for topical application, not intra-articular injection.
However, this argument is not deemed persuasive. Hunter et al. (‘202) teach an anti-angiogenic factor being formulated in topical ocular composition (paragraph 194); “the anti-angiogenic compositions described above may be injected directly into the corneal stroma” (paragraph 196); an anti-angiogenic factor being formulated in a surgical paste for joint injection (paragraph 165); and a surgical paste comprising microspheres in form of suspension (paragraph 281). Thus, a topical composition in form of microspheres suspension can be used for injection either to corneal stroma or joint.
Applicants argue that the claimed >10 µm particle size matters with regard to toxicity according to the instant specification paragraph 15 and 36 while Hunter et al. (‘202) teach particle size of 0.1-500 µm.
However, this argument is not deemed persuasive. The instant specification paragraph 15 discloses local toxicity in the muscle layers overlying and fed by arteries infused with the microparticles containing colchicine or colchicine analogue but not control microparticles in the discussed publications which have lower particle size relative to the instant invention while paragraph 36 discloses effective local dose, not toxicity as a result of lower than claimed particle size. Thus, there is neither clear disclosure of particle size <10 µm as the cause for toxicity nor factual support of particle size <10 µm as the cause for toxicity; while Hunter et al. (‘202) teach microspheres with size of 10-30 µm (paragraph 120 and 263).
Applicants argue that Hunter et al. (‘280) teach nanoparticles which would result in toxicity.
However, this argument is not deemed persuasive.
First, as discussed above, there is neither clear disclosure of particle size <10 µm as the cause for toxicity nor factual support of particle size <10 µm as the cause for toxicity.
Second, this is a 35 USC 103(a) rejection and not a 35 USC 102 rejection and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claims are allowed.
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 extension fee 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 HONG YU whose telephone number is (571)270-1328. The examiner can normally be reached on 9 am - 5:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached on 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HONG YU/
Primary Examiner, Art Unit 1614
