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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments, see Pg 5-7, filed 8/3/2026, with respect to the rejection of claim 5 under 35 U.S.C. 112(b), have been fully considered and are persuasive. The rejection has been withdrawn.
Applicant’s arguments, see Pg 8-11, filed 8/3/2026, with respect to the rejection(s) of the claims under 35 U.S.C. 103, have been fully considered and are persuasive. Specifically, in view of the amended claim set, Applicant’s argument that Sanda teaches longer-lasting (>two weeks) gelatin microparticles that would not dissolve within the timeframe set forth in the current claims is found persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of further search and examination of the amended claims.
Claim Status
Claims 1-2 and 5-10 are pending under examination and currently amended. Claims 2 and 3 are cancelled. Claims 1 and 5-7 are currently amended.
Priority
The instant application is the 371 national stage entry of PCT/KR2021/013153, filed 9/27/2021, which claims priority to KR10-2021-0063534, filed 5/17/2021. The priority date of 5/17/2021 is acknowledged although it is noted that no translation has been made of record.
Claim Objections
Claim 5 is objected to because of the following informalities: amend line 2 such that it reads insert an “or” such that the claim reads “24 hours, or 98% at 48 hours after the dissolution starts in the normal saline” (emphasis added) for improved readability. Appropriate correction is required.
Claim Interpretation
Claim 1 recites that a subject is injected with an embolic material. The instant specification does not define a subject, so it is being interpreted as open to any organism or system in which an embolic material can be injected.
Claim 7 recites that the gelatin particles are injected into a blood vessel and embolized, thereby relieving or treating pain in the musculoskeletal system. This limitation describes a functional outcome that occurs as a result of practicing the instantly claimed method. As such, the claim is being interpreted based upon the structural limitation (injecting, to a subject, an embolic material comprising gelatin particles), where the functional limitation is endowed by the structure. Claim 1 has been amended to similarly recite “wherein the embolic material is embolized in the blood vessel” and is also being interpreted in this same manner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As described above in the Claim Interpretation section, claim 7 recites only a functional outcome that is already recited in amended claim 1. For this reason, claim 7 does not further limit from claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claim(s) 1, 2, 5, 6, 7, 9, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Yamagami et al. (Selective arterial embolization with gelatin particles for refractory knee hemarthrosis. Diagn Interv Radiol. 2013 Sep-Oct;19(5):423-6.). in view of Takasaka et al. (A New Soluble Gelatin Sponge for Transcatheter Hepatic Arterial Embolization. Cardiovasc Intervent Radiol 33, 1198–1204 (2010)).
Yamagami teaches arterial embolization as a method of treating refractory knee hemathrosis (Title, Abstract). Yamagami further teaches that the patients treated had pain and swelling of the knee (Pg 423, “Materials and methods”, first paragraph).
Yamagami teaches that transarterial embolization was performed under local anesthesia and a catheter was inserted from which gelatin particles (the embolic material) were infused (injected).
Yamagami does not teach that the gelatin particles have a solubility rate of 50% or more at 48 hours after dilution starts in normal saline nor that the gelatin particles are thermally crosslinked at a temperature of 130°C or above.
Takasaka teaches gelatin sponge particles (gelatin particles) as an embolic material. In the context of hepatocellular carcinoma, it is believed that embolization using gelatin sponge particles increases the long-term survival rate of patients. However, gelatin particles commonly cause occlusion of the hepatic artery. Gelatin particles available for transcatheter hepatic arterial embolization (THAE) are insoluble and are reported to be absorbed and/or embedded in the arterial wall, as is the biological response to a foreign body. This response results in occlusion or stenosis with a narrow diameter even if the hepatic artery is recanalized. The development of soluble gelatin particles with an appropriate duration of occlusion would enable tumor ischemia while avoiding the occlusion and/or stenosis of the hepatic artery that may occur with embolization, and would inhibit the development of collateral pathways (Pg 1198-1199, “Introduction”).
Takasaka teaches preparation of gelatin with heat cross-linkage (thermal crosslinking) using gelatin of different molecular weights. A gelatin sponge is generated and then dry-heat sterilized for 24 hours to cause heat-induced cross-linkage, wherein the dry-heat sterilization is performed at temperatures of 110°C, 120°C, 125°C, 130°C, 135°C, 138°C, and 150°C. After heat-induced cross-linkage, the gelatin sponges were sliced into 1-2mm particles. The solubility of the particles was examined by placing 100mg into 10ml of saline at 37°C (Pg 1199, “Preparation of the Gelatin with Heat Cross-linkage” and “Soluble Time of RM-GSP In Vitro”). Table 1 indicates that gelatin particles consisting of the 50kDa gelatin generated via heat-induced cross-linking at temperatures of 130°C and 135°C dissolve within 6 (+/-1.7hours) and 57.7 hours (+/-9.8hours), respectively, which would result in the solubility of 50% or more of the gelatin particles at 48 hours after dissolution begins. Moreover, Takasaka demonstrates that recanalization of embolized hepatic artery after transcatheter arterial embolization with gelatin particles thermally crosslinked at 135°C occurs within 48 hours in swine with no adverse effects (Table 2; Pg 1203, “Discussion,” second and third paragraphs).
In summary, Yamagami teaches a method of relieving or treating musculoskeletal pain by injecting an embolic material comprising gelatin particles into blood vessels. Takasaka teaches that a common problem associated with embolic administration of gelatin particles is occlusion of the hepatic artery due to the insolubility of said particles. To overcome this problem, Takasaka teaches generating gelatin particles through thermal crosslinking at varying temperatures and identifies multiple candidate gelatin particles that can be administered as embolic material that dissolve within a few days.
Based upon these teachings, regarding claims 1 and 7, it would be obvious to incorporate the gelatin particles of Takasaka into the method taught by Yamagami. One skilled in the art would be motivated to do so in order to reduce the likelihood of artery occlusion due to particle insolubility. One would have a reasonable expectation of success as Takasaka teaches multiple gelatin particles for embolization that dissolve rapidly (are not insoluble for more than 2 weeks) with no adverse effects, such as those thermally crosslinked at 130°C or 135°C.
Regarding claim 2, Yamagami teaches that the gelatin particles were either 1-2mm; 1mm is equivalent to 1000µm (Pg 423, “Materials and methods”, first paragraph - Pg 424, left and middle columns). Further, Takasaka teaches the particles can range from 1-2mm (1000μm; Pg 1199, left column, “Preparation of the Gelatin with Heat Cross-linkage”).
Regarding claim 5, Takasaka teaches the gelatin particles thermally crosslinked at 130°C dissolve after 6 hours, +/-1.7hours (Table 1). This would necessarily mean that 89% or more of the gelatin particles are dissolved at 3 hours and/or 92% or more of the gelatin particles are dissolved at 24 hours.
Regarding claim 6, as stated above, Yamagami teaches that the patients treated had knee pain (Pg 423, “Materials and methods”, first paragraph).
Regarding claim 9, Yamagami teaches that the injection occurred through the femoral artery (Pg 423, “Materials and methods,” second paragraph).
Regarding claim 10, Yamagami teaches that the median duration of hemarthrosis was 9 months (range, 2-17 months), which reads on pain lasting for a median duration of 6 months or more (Pg 423, “Materials and methods,” first paragraph; Table 1).
Claim(s) 1, 2, and 5-10 rejected under 35 U.S.C. 103 as being unpatentable over Yamagami et al. (Selective arterial embolization with gelatin particles for refractory knee hemarthrosis. Diagn Interv Radiol. 2013 Sep-Oct;19(5):423-6.). and Takasaka et al. (A New Soluble Gelatin Sponge for Transcatheter Hepatic Arterial Embolization. Cardiovasc Intervent Radiol 33, 1198–1204 (2010), as applied to claims 1, 2, 5, 6, 7, 9, and 10 above, and further in view of Li et al. (KR20200066574A, published 6/10/2020, rejection based on English translation; cited on IDS filed 9/27/2023).
The teachings of Yamagami and Takasaka have been set forth above. Yamagami and Takasaka do not teach injecting a mean amount of 10-500mg of gelatin particles.
Li teaches microparticles comprised of gelatin loaded with anticancer drugs and methods of treatment thereof (Abstract; [0008]). Li teaches preparing 100-300mg of gelatin microspheres loaded with drugs that can then be injected into subjects in need thereof (Examples 4-9 and 13).
In summary, Yamagami and Takasaka teach a method of relieving or treating musculoskeletal pain by injecting an embolic material comprising thermally crosslinked gelatin particles into blood vessels. Li teaches preparing 100-300 mg of gelatin microspheres for injection into subjects in need thereof. Based upon these teachings, regarding claim 8, it would be obvious to administer 100-300mg of gelatin particles in the method taught by Yamagami and Takasaka. One skilled in the art would be motivated to do so because one would recognize that 100-300mg is a good starting point from which one could further optimize the dosage administered depending on the patient and treatment required. One would have a reasonable expectation of success as Li teaches administering gelatin particles as a means of treating disease through transcatheter arterial chemoembolization, similar to Yamagami and Takasaka.
Conclusion
No claim is 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 (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.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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