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 .
Claims 1-20 are pending and have been considered on the merits.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-4 and 9-20 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims disclose a step of providing an intra-articular administration of an agent capable of decreasing debris found in the articular space.
The scope of “an agent capable of decreasing debris found in the articular space” is extensively broad. The “agent” capable of decreasing debris has the scope that is not limited and it is dependent on the type of “debris” in the articular space. As the “debris” found in the articular space is not clearly defined, the “agent” capable of decreasing the debris would be unlimited.
The instant specification does not particularly define what the debris is and thus, what the scope of the agent that can decrease the debris. While the specification discloses the agent being hyaluronidase or a protease, the debris would be limited to hyaluronic acid or protein, however, claim 1 and its dependent claims do not particularly limit the scope of the “debris” and thus the “agent”.
There is no disclosure with regard to the other “debris” considered to be present in the articular space. For example, the term “loose bodies” is known in the art that is referring to a fragment of bone or cartilage within a joint’s articular space (see Melrose, 2016, Eur. J. Histochem.). Thus, the “debris” could be any materials accumulated in the articular space not only cartilage but also bone fragment. Maletis et al. (2002, Arthroscopy) teach that the debris can be intra-articular metal debris seen in the patients after completion of an endoscopic anterior cruciate ligament reconstruction (see Abstract).
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
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.
Claims 11, 13 and 16-19 are 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 11 discloses the term “bone marrow aspirate/mononuclear cells”. It is not clear what the scope of this term points out. It is vague whether the term is referring to “bone marrow aspirate” or “mononuclear cells”, or mononuclear cells derived from bone marrow aspirate. Clarification is required.
Claim 13 discloses the term “inducible pluripotent stem cells” in line 1. It is not clear what the term “inducible” intends to point out. Is it supposed to be “induced” instead or if not, it is vague what would be inducible in the pluripotent stem cells. Metes and bounds of the term is unclear. Clarification is required.
Claim 16 discloses that the interferon gamma is administered at a concentration of 5 ng/ml for a period of 1 hour to 24 hours, and claim 16 is dependent on claim 15. It is not clear if this limitation is an active step for the claimed method or an optional limitation. Furthermore, it is not clear if the IFN-g is administered to the MSCs prior to the step (c) of claim 1, or it is administered to the patient after the step (c) or even before the step (c). Clarification is required.
Claim 17 and its dependent claims recites the limitation "said agents" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 17 is dependent on claim 1 and claim 1 discloses only “an agent” and thus, there is no support for the term “agents”.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 5-7, 9-10, 12 and 14-17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Naughton et al. (US 5,842,477) as evidenced by Docheva et al. (2008, Current Rheumatology Reviews) and Vincenti et al. (2002, Arthritis Research & Therapy).
Regarding claims 1-2, 5-6 and 12, Naughton et al. teach a method of treating or repairing cartilage in vivo comprising administration of a preparation of stromal cells including chondrocyte progenitor cells including mesenchymal stem cell (col. 5, line 66- col. 6, line 13). Thus, this teaching would meet the step (c) of claim 1.
Regarding step (a) of claim 1, as the method of Naughton et al. requires patients suffering from degenerative connective tissue diseases such as rheumatoid and/or osteoarthritis (col. 1, lines 31-35), the administering the MSCs into the patients would necessarily meet the step of identifying a patient in need of therapy.
Regarding step (b) of claim 1, Naughton et al. teach that the defect site is treated, preferably prior to implantation, to degrade the cartilage at the site of the defect, and this treatment is carried out using enzymes including trypsin (protease; RE: claim 6), collagenase, elastase, and/or hyaluronidase (col. 10, lines 1-9). This teaching would meet the step (b) of administering an agent capable of decreasing debris found in the articular space. Regarding the intra-articular administration of the agent, Naughton et al. is silent where the enzyme being treated, however, as the enzyme degrades the cartilage at the site of the defect, a person skilled in the art would have at once envisaged to administer the enzyme via an intra-articular administration.
Regarding claim 7 directed to the protease being metalloprotease, while Naughton et al. do not particularly disclose metalloprotease, however, they teach collagenase (col. 10, lines 1-10), and collagenase is a matrix metalloprotease according to Vincenti et al. (see Abstract).
Regarding claims 9-10 directed to the cell population being autologous or allogeneic, Naughton et al. teach that the stromal cells can be obtained from the patient or a histocompatible donor (col. 10, lines 43-44), and this teaching would meet autologous (claim 9) and allogeneic (claim 10).
Regarding claim 14 directed the MSCs expressing IL-1 receptor, it is submitted that it is the inherent characteristics of MSCs to express IL-1 receptor according to Docheva et al. (see p.2, Cytokine Receptors).
Regarding claim 15 directed to the MSCs express IL-1 receptor antagonist when treated with interferon gamma, this wherein clause does not require any active step to be performed for the claimed method, and thus, it does not provide patentable weight in determining the patentability of the claimed method.
Regarding claim 16, the wherein claim discloses a step of administering IFNg at 5 ng/ml for 1-24 hours. This wherein clause is dependent on claim 15 which has been considered not limiting because it does not require any active step to be carried out. Thus, even though the wherein clause of claim 16 discloses a step, however, it is interpreted an optional that is not required to be performed (see MPEP2111.04(I)).
Regarding claim 17, Naughton et al. teach that bioactive agents such as growth factors are included at the implantation site along with the stem cells (col. 4, lines 44-58; col. 13, lines 1-5).
Thus, the reference anticipates the claimed invention.
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) 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-7, 9-10, 12 and 14-17 above, and further in view of Rodrigues et al. (2010, Rev. Bras. Ortop.).
Regarding claims 1-2, 5-7, 9, 12 and 14-17, Naughton et al. anticipate the subject matter and thus render them obvious.
Regarding claims 3-4 directed to the identification of a patient by assessing cartilage erosion, and the assessing is performed by MRI, Naughton et al. do not teach the limitation.
However, it would have been obvious to a person skilled in the art to identify the patients having cartilage degeneration by determining cartilage erosion detected by MRI because it is well known procedure to diagnose cartilage defect according to Rodrigues et al. Rodrigues et al. teach that the MRI is the best noninvasive method for assessing the joint cartilage and detects chondral erosion (see Fig. 5).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-7, 9-10, 12 and 14-17 above, and further in view of Vincenti et al. (supra)
Regarding the protease being a matrix metalloprotease and the metalloprotease being MMP13, Naughton et al. do not teach the limitation. However, Naughton et al. teach the use of collagenase (col. 10, lines 1-9), and it is known in the art that collagenase is a matrix metalloprotease according to Vincenti et al. Vincenti et al. teach that MMP-1, MMP-8 and MMP-13 are interstitial collagenases that degrade type II collagen in cartilage (abstract).
It would have been obvious to a person skilled in the art to use MMP13 for the collagenase as taught by Vincenti et al. utilized by the method of Naughton et al. with a reasonable expectation of success as one skilled in the art would recognize that MMP-13 which is one of known collagenases can be utilized for the method of Naughton et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-7, 9-10, 12 and 14-17 above, and further in view of Cotter et al. (2018, Cartilage)
Regarding claim 11 directed to the cell population being bone marrow aspirate, Naughton et al. do not particularly teach the limitation.
It would have been obvious to a person skilled in the art to use bone marrow aspirate for the method of Naughton et al. as a composition comprising chondrocyte progenitor cells because Naughton et al. teach that the stromal cells including MSCs are derived from bone marrow (col. 10, lines 53-55; col. 19, lines 33-46), and Cotter et al. teach the use of bone marrow aspirate concentrate (BMAC) that contains MSCs as well as growth factors for cartilage defects of the knee (Abstract).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-7, 9, 12 and 14-17 above, and further in view of D’Lima et al. (US 2015/0283303)
Regarding claim 13 directed to the cell population being induced pluripotent stem cells, Naughton et al. do not particularly teach the limitation. It is noted that “inducible pluripotent stem cell” is interpreted as “induced pluripotent stem cell”.
D’Lima et al. teach that the combination of chondrocytes, chondroprogenitor cells, mesenchymal stem cells, induced pluripotent stem cells (iPSCs) or any combinations thereof is utilized for a method treating cartilage defects or cartilage related disorder (para. 13, Example 4). D’Lima et al. teach that the cartilage related disorder includes osteoarthritis (para. 17).
It would have been obvious to a person skilled in the art to use iPSCs along with MSCs in the method of Naughton et al. with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because D’Lima et al. teach that MSCs can be mixed in combination along with iPSCs and chondrocytes in the method of treating osteoarthritis. Thus, one skilled in the art would try the combination of MSCs and iPSCs for the method of Naughton et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 15-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-7, 9, 12, 14 and 17 above, and further in view of Montesinos et al. (2020, J. Immunol. Res.) and Zhao et al. (2020, Front. Bioeng. Biotechnol.)
Regarding claim 16, while the limitation of claims 15-16 have been addressed as non-limiting because no active step required to be performed.
However, if it is considered that claims 15-16 are considered as an active step of administering interferon gamma being administered at the concentration of 5 ng/ml for 1-24 hours, and the MSCs would result in expressing IL-1 receptor antagonist, Naughton et al. do not teach the limitations.
However, Montesinos et al. teach that bone marrow MSCs exposed to IFN-g at 5 ng/ml for 24 hours resulted in the increase of ICAM-1 and HLA-1 expression (Fig. 3). Montesinos et al. also teach that the BM-MSCs exposed to IFN-g release microvesicles (MVs) enriched in ICAM-1 (p.10, 1st col., 3.6.). Montesinos et al. teach that ICAM-1 is a fundamental molecule in the immunoregulatory function of MSCs because it mediates cell-cell interaction (p.12, 2nd col., 2nd last para.).
It would have been obvious to a person skilled in the art to treat the MSCs of Naughton et al. with 5 ng/ml of IFN-g to enhance the immunomodulatory properties of the MSCs. A person of ordinary skilled in the art would have been motivated to do so because the increased immunomodulatory properties of MSCs are beneficial in treating osteoarthritis according to Zhao et al. (see entire document).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-7, 9, 12 and 14-17 above, and further in view of Hua (WO2015085957; English translation attached)
Regarding claims 18-19 directed to the growth factor of claim 17 being HGF or EGF, Naughton et al. do not teach the limitation.
Hua teaches a composition for treating osteoarthritis (OA), and the composition includes the mesenchymal stem cell culture supernatant comprising EGF and HGF (p.2, claim 7; p.3).
It would have been obvious to a person skilled in the art to use the MSC culture supernatant comprising HGF and/or HGF along with the MSCs as the growth factors present in the MSC culture supernatant are useful for treating OA and thus, one skilled in the art would combine the MSCs and MSC culture supernatant (i.e. conditioned medium) together and administer for treating OA with a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naughton et al. (supra) as applied to claims 1-2, 5-6, 9, 12 and 14-17 above, and further in view of Prodromos et al. (2019, Medicines)
Regarding claim 20 directed to the cell population being administered before or after intraarticular laser treatment, this limitation does not require an active step of treating the patient using intraarticular laser therapy. Rather the limitation is considered as optional.
Even if it is considered that the laser treatment is required by the claimed method, intra-articular laser treatment is known in the art according to Prodromos et al. for treating osteoarthrosis (see Abstract).
It would have been obvious to a person skilled in the art to combine the laser treatment taught by Prodromos et al. with the method of Naughton et al. for the same purpose with a reasonable expectation of success. By combining the teachings one skilled in the art would recognize that the laser treatment can be either before or after the method of Naughton et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631