DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim set filed 12/2/2024 with claims 1-13 is pending.
The instant application is a continuation of International Application No. PCT/KR2023/006062 filed on May 3, 2023, which claims priority to Korean Patent Application No. 10-2022-0072957 filed on June 15, 2022.
The priority document has been received but is not in English and therefore applicants cannot rely on the filing date of this document. The effective filing date of the claims is, therefore, May 3, 2023.
Information Disclosure Statement
An IDS filed 12/2/2024 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action.
Claim Objections
Claim 5 is objected to because of the following informalities: each limitation requires its own article and therefore “15% w/v%” should be preceded by the article “a”. Claim 9 is objected to as the abbreviation emu/g should be spelled out. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 is unclear as to the reference to autologous stem cells as (bone marrow stem cells, adipose derived stem cells). It is unclear if these are examples of autologous stem cells or a limiting definition. Similarly, it is not clear if TGF-beta is the only pain and inflammation relieving factor intended by the claim.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention is directed to methods of making a hydrogel microbead as well as the hydrogel microbead and pharmaceutical compositions thereof. Claim 1 is drawn generically to steps of production that include electrospinning sodium alginate, a biocompatible polymer and magnetic particles which are cured and freeze-dried. This disclosure teaches,
Specifically, hyaluronic acid and sodium alginate solutions were prepared separately, and then mixed with magnetic particles according to a mixing ratio. A mixed solution including hyaluronic acid, sodium alginate, and magnetic particles composed of iron oxide was placed in an electrospinning equipment to produce beads under the set spinning conditions (frequency (Hz), voltage (V), and temperature (°C)) (Table 1).
But proposes polyester based biocompatible polymers specifically citing hyaluronic acid and chitosan (see ¶ 0011). As to the step of curing, the method requires divalent metal ions at a concentration and time demonstrated to be 1 w/v% to 15 w/v% calcium salt solution for 30 minutes to 48 hours.
[0014] If the concentration of the calcium salt solution used and the treatment time are lower than the given conditions, insufficient time is allowed for ionic cross-linking and thus intact microbeads are not formed. On the other hand, if the conditions are higher than the given conditions, more ionic crosslinking will occur than necessary, resulting in the microbeads clumping together or deforming.
The claims as recited rely on generic language which is not supported by the specification. The number of embodiments disclosed in the specification must be commensurate with the magnitude of the claimed genus, particularly if the genus is to cover species that are not known in the prior art. Here, the specification describes a single species that mediates the effect. But, the claims recite the construct in generic terms. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is needed. Since the disclosure fails to describe common attributes or characteristics that identify members of the genera, and because the genera are highly variant.
Remaining dependent claims also lack adequate description., Claim 7 recites a structure property without details as to how it is achieved. This is true of claims 8 and 9. Claim 7 requires that the microbeads contains 30-70% wt% of magnetic particles.
The content of magnetic particles in microbeads plays the biggest role as a parameter in product functionality, such as a shape and a size of the beads, the carrying rate of therapeutic substances, and actuation performance of the beads.
Hence, the steps to claim 7 are limited compared to the claims but apparently necessary. As to claim 9 that requires the magnetic strength of 15 emu/g to 40 emu/g, neither the claims not the disclosure provide the means to accomplish this. Hence, this is a goal without a step to guide the practitioner. This is true of claim 8 which requires that the hydrogel swelling degree is 400-1,800%. This appears to be achieved by controlling factors of ration polymer:alginate as well as ion curing time.
0012] In addition, the shape, swelling degree, and mobility properties of the microbeads produced may be controlled according to the mixing ratio of sodium alginate and the biocompatible polymer in the mixed solution provided in the electrospinning process. For example, it is preferable that the mixed solution includes 4 to 100 parts by weight of a biocompatible polymer based on 100 parts by weight of sodium alginate.
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Claim 11 recites a potential use of the composition recited in claim 11 wherein by limiting the type of cartilage disease does not change the structure of the microbeads. It simply recites a desired function without a correlative structural change.
As set forth above, the specification does not provide adequate guidance of the structural requirements and hence the claims also lack Written Description such that a person of skill in the art would recognize that they were in possession of the genus of methods and resulting microbeads made according to the more specific embodiments in the disclosure. The MPEP teaches, “However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971). (see MPEP 2164.08(b)). Given the large size and diversity of biocompatible polymers, curing methods and means to produce the microbeads: and the inability to determine which will also have the essential properties, it is concluded that the invention must be empirically determined. In an unpredictable art, the disclosure of no species would not represent to the skilled artisan a representative number of species sufficient to show applicants were in possession of claimed genus.
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 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.
Claims 1, 3, 6 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Babaniamansour et al (BioMed Research International, 2022, pages 1-12) in view of Hasturk et al (US 2024/0368538) and Xie and Boda (US 20210212949).
Babaniamansour et al review the art of treating cartilage injuries and the use of magnetic hydrogels (see abstract). These hydrogels are based in polymers such as hyaluronic acid as well as therapeutic components i.e. mesenchymal stem cells (see page 6, col 2). Magnetic inclusion was found to provide a number of advantages in control and noncontact manipulative approaches (see page 8, col 1).
This review lacks details on how the microbeads are formed but such information is obtained from the art. Xie and Boda teach microspheres that are used for treating arthritis and cartilage issues (see e.g. ¶0041). The beads are formulated from polymers, alginate and subjected to electrospray with a spray nozzle (see e.g. ¶0090). The method further entailed crosslinking and freeze-drying (see figure 1). The method does not include magnetic particles nor ionic crosslinking.
Hasturk et al teach similarly, microbeads to treat arthritis or provide cartilage repairs (see e.g. ¶0004). The microbeads are composed of alginate that encapsulate mammalian cells. To increase survival under elevated pressure, the beads are cured by ionic cross-linking (see cross-linking).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the dynamics of ionic cross linking as well as freeze drying as taught by Xie and Boda and Hasturk et al to the method of Babaniamansour et al. As noted above: 1) Babaniamansour et al, Xie and Boda and Hasturk at al provide methods for forming and using hydrogel microbeads wherein Babaniamansour et al teaches that magnetic formulations are improved for therapeutic use; 2) Xie and Boda teach benefits of crosslinking and freeze drying while 3) Hasturk et al each ionic crosslinking for improved survival under pressure. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the adjustments would provide stable, stable products.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Babaniamansour et al (BioMed Research International, 2022, pages 1-12) in view of Hasturk et al (US 2024/0368538) and Xie and Boda(US 20210212949)as applied to claims 1, 3, 6 and 10-13 above, and further in view of Giron-Hernandez et al (Carbohydrates Polymers, 2021, pages 1-8).
Giron-Hernandez teaches the conditions under which calcium crosslinking occurs wherein 2.5% calcium salt is incubated for 24 hours thus meeting the conditions of claim 5. Importing the conditions of Giron-Hernandez would have provided “Improved barrier properties were also observed in more homogeneously and extensively crosslinked calcium alginate beads, as indicated by the enhanced chemical stability of β-carotene in 0.5% alginate samples”. Thus a person of skill in the art would have consulted and incorporated the method of Giron into the method of Babaniamansour et al in view of Hasturk and Xie and Boda.
Conclusion
Claims 2 and 7-9 appear to be free of the art.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634
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