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 .
Status of Claims
Cancelled: 1-20
New: 21-31
Examined Herein: 21-31
Note : Claim 21 must be amended to start with a capital letter.
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PRO 63/340,828 on 5/11/2022.
Withdrawn Rejections
All rejections of claims 1-20 are hereby withdrawn; their cancellation moots the rejections.
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.
Claims 21, 22, 24, 25, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Hao (US 2022/0062346 A1, Published 3/3/2022), in view of Niazi (US 2021/0024893 A1, Published 1/28/2021).
With respect to claim 21, Hao discloses a method of treating a patient diagnosed with osteoarthritis, comprising:
a) identifying a patient diagnosed with osteoarthritis;
b) obtaining a synovial tissue biological sample from the patient;
c) collecting exosomes from the biological sample;
d) detecting, in the collected exosomes, the presence or level of MiRNA-155; and
e) administering a therapeutic amount of mesenchymal stem cells to treat said osteoarthritis in the patient. [Hao, 0027-0030 & 0033-0041, 0047-0050]
The limitation “if the patient's level of MiRNA-155 is lower than a predetermined reference level” is a conditional limitation that does not distinguish the claimed invention from the prior art, as Hao discloses performing the administration step, thereby satisfying the condition precedent.
With respect to claim 22, Hao discloses the stem cells are derived from synovial mesenchymal stem cells. [Hao, 0028-0030, 0035]
With respect to claim 24, Hao discloses the exosomes are collected by ultracentrifugation (centrifugal force 100000 r/min). [Hao, 0034]
With respect to claim 29-30, Hao discloses detecting the level of miRNA-155 comprises
performing a nucleic acid amplification assay, quantitative PCR. [Hao, 0042, 0043]
Hao does not disclose a biological fluid sample is obtained.
However, with respect to claim 21, Niazi discloses a method of treating a patient diagnosed with osteoarthritis, comprising:
a) identifying a patient diagnosed with osteoarthritis;
b) obtaining a synovial fluid biological sample from the patient;
c) collecting exosomes from the biological fluid sample; and
e) administering a therapeutic amount of mesenchymal stem cells to treat said osteoarthritis in the patient. [Niazi, 0030, 0110, 0144-0147, 0164-0168, 0183-0185]
With respect to claim 22, Niazi discloses the stem cells are derived from adipose tissue. [Niazi, 0183-0184] However, Niazi further discloses mesenchymal stem cells may be derived from bone marrow. [Niazi, 0122]
With respect to claim 24, Niazi discloses the exosomes may be collected by ultracentrifugation (differential ultracentrifugation). [Niazi, 0135]
With respect to claim 25, Niazi discloses the exosomes may be collected by affinity capture using an immobilized antibody (immunoaffinity capture). [Niazi, 0136]
With respect to claim 31, Niazi discloses the biological fluid sample is synovial fluid, which is an ultrafiltrate of plasma. [Niazi, 0143-0147]
Modifying the method disclosed by Hao by obtaining a synovial fluid sample from the patient, rather than a synovial tissue sample, results in the method of claim 21 and 31.
Modifying the method disclosed by Hao by administering mesenchymal stem cells derived from bone marrow results in the method of claim 22.
Modifying the method disclose by Hao collecting the exosomes by immunoaffinity capture using an immobilized antibody results in the method of claim 25.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Hao by obtaining a synovial fluid sample from the patient, rather than a synovial tissue sample, and have a reasonable expectation of success. Hao discloses a method comprising collecting exosomes from a synovial tissue sample obtained from a patient diagnosed with osteoarthritis (OA). Niazi discloses a method comprising collecting exosomes from a synovial fluid sample obtained from a patient diagnosed with OA. Thus, Niazi establishes that synovial fluid is an acceptable biological sample for exosome collection in patients diagnosed with osteoarthritis. Accordingly, the combined teachings of Hao and Niazi suggest that in the method disclosed by Hao, the exosomes may be collected from a synovial fluid sample obtained from the patient. Therefore, it is reasonable to expect the method disclosed by Hao may be modified by obtaining a synovial fluid sample from the patient. One would have been motivated to do so because substituting equivalent exosome sources known for the same purpose when the equivalency must be recognized in the prior art, is prima facie obvious. MPEP 2144.06(II). In the present case, Niazi discloses exosomes are found in blood and other bodily fluids, including synovial fluid. [Niazi, 0013] Therefore, substituting one known exosome source (synovial tissue) in the method disclosed by Hao, for another (synovial fluid), is prima facie obvious.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Hao by administering mesenchymal stem cells derived from bone marrow to the patient and have a reasonable expectation of success. Hao discloses a method of treating a patient diagnosed with osteoarthritis (OA) comprising administering a therapeutic amount of mesenchymal stem cells (MSCs) derived from synovial tissue to the patient. Niazi discloses a method of treating a patient diagnosed with OA comprising administering a therapeutic amount of MSCs derived from adipose tissue or bone marrow to the patient. Thus, Niazi establishes that MSCs derived from bone marrow may be used to treat OA in a patient in need thereof. Accordingly, the combined teachings of Hao and Niazi suggest that in the method disclosed by Hao, MSCs from bone marrow may be used to treat OA in the patient. Therefore, it is reasonable to expect the method disclosed by Hao may be modified by administering mesenchymal stem cells derived from bone marrow to the patient. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Niazi discloses adult stem cells derived from bone marrow administered to a subject diagnosed with an inflammatory disease or disorder, including osteoarthritis, will inhibit or downregulate inflammation in the treated subject. [Niazi, 0110, 0113, 0138] Therefore, one would have been motivated by the expectation that administering MSCs derived from bone marrow to the patient of the method disclosed by Hao will inhibit or downregulate inflammation in the patient.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Hao collecting the exosomes via immunoaffinity capture using an immobilized antibody and have a reasonable expectation of success. Hao discloses a method comprising collecting exosomes from a biological sample obtained from a patient diagnosed with osteoarthritis (OA) via ultracentrifugation. Niazi discloses a method comprising collecting exosomes from a biological sample obtained from a patient diagnosed with OA using methods known in the art, including differential ultracentrifugation or immunoaffinity capture using an immobilized antibody. Thus, Niazi establishes that exosomes may be collected via art-known methods including differential ultracentrifugation or immunoaffinity capture are well-established techniques in the art. Accordingly, the combined teachings of Hao and Niazi suggest that in the method disclosed by Hao, the exosomes may be collected via immunoaffinity capture. Therefore, it is reasonable to expect the method disclose by Hao may be modified by collecting the exosomes via immunoaffinity capture using an immobilized antibody. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Niazi discloses immunoaffinity capture overcomes the problem of immune-complex contaminants and other possible contamination and the eluted captured exosomes are intact and bioactive. [Niazi, 0136, 0178-0180] Therefore, one would have been motivated by the expectation that collecting the exosomes via differential ultracentrifugation or immunoaffinity capture in the method disclosed by Niazi could minimize contamination and elute captured exosomes that are intact and bioactive.
Claims 21-25 and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Hao and Niazi, as applied to claim 21, 22, 24, 25, and 29-31 above, and further in view of Pettine (US 2018/0104280 A1, Published 4/19/2018).
With respect to claim 21 and 22, Hao and Niazi disclose the teachings above.
Hao and Niazi do not disclose the bone marrow derived mesenchymal stem cells comprise bone marrow mononuclear cells.
However, with respect to claim 22, Pettine discloses a method of treating a patient diagnosed with osteoarthritis, comprising:
a) identifying a patient diagnosed with osteoarthritis; and
e) administering a therapeutic amount of mesenchymal stem cells to treat said osteoarthritis in the patient. [Pettine, 0024-0027, 0029, 0030]
Pettine discloses the mesenchymal stem cells (MSC’s) are isolated from bone marrow. [Pettine, 0067-0068]
With respect to claim 23, Pettine discloses the bone marrow derived mesenchymal stem cells comprise bone marrow mononuclear cells. [Pettine, 0067-0068]
Modifying the method disclosed by Hao and Niazi by administering bone marrow derived mesenchymal stem cells comprising bone marrow mononuclear cells results in the method of claim 22 and 23.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Hao and Niazi by administering mesenchymal stem cells (MSCs) derived from bone marrow comprising bone marrow mononuclear cells to the patient and have a reasonable expectation of success. Hao and Niazi disclose a method of treating a patient diagnosed with osteoarthritis (OA) comprising administering a therapeutic amount of MSCs derived from synovial, adipose tissue, or bone marrow to the patient. Pettine discloses a method of treating a patient diagnosed with OA comprising administering a therapeutic amount of MSCs derived from bone marrow comprising bone marrow mononuclear cells. Thus, Hao and Niazi establish that MSCs derived from various sources may be administered to treat OA and Pettine establishes that MSCs derived from bone marrow comprising bone marrow mononuclear cells may be administered to treat OA. Accordingly, the combined teachings of Hao/Niazi and Pettine suggest that in the method disclosed by Hao/Niazi, MSCs derived from bone marrow comprising bone marrow mononuclear may be used to treat OA in the patient. Therefore, it is reasonable to expect the method disclosed by Hao and Niazi may be modified by administering MSCs derived from bone marrow comprising bone marrow mononuclear to the patient. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Pettine discloses that MSCs derived from bone marrow comprising bone marrow mononuclear cells are preferred because they are an excellent source of MCSs, as the MSCs are stored in bone marrow. [Pettine, 0027] Moreover, Pettine discloses MSCs derived from bone marrow comprising bone marrow mononuclear cells are believed to reduce inflammation associated with OA of the knee joint by differentiating into osteoblasts, and restoring the damaged medial tibial metaphysis to a normal physiologic structure. [Pettine, 0030] Therefore, one would have been motivated by the expectation that administering MSCs derived from bone marrow comprising bone marrow mononuclear cells to the patient in the method disclosed by Hao and Niazi could restore the affected joint structure to a normal physiologic structure.
Claims 21 and 24-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hao, in view of Newman (US 2016/0320390 A1, Published 11/3/2016).
With respect to claim 21, Hao discloses a method of treating a patient diagnosed with osteoarthritis, comprising:
a) identifying a patient diagnosed with osteoarthritis;
b) obtaining a synovial tissue biological sample from the patient;
c) collecting exosomes from the biological sample;
d) detecting, in the collected exosomes, the presence or level of MiRNA-155; and
e) administering a therapeutic amount of mesenchymal stem cells to treat said osteoarthritis in the patient. [Hao, 0027-0030 & 0033-0041, 0047-0050]
The limitation “if the patient's level of MiRNA-155 is lower than a predetermined reference level” is a conditional limitation that does not distinguish the claimed invention from the prior art, as Hao discloses performing the administration step, thereby satisfying the condition precedent.
With respect to claim 24, Hao discloses the exosomes are collected by ultracentrifugation (centrifugal force 100000 r/min). [Hao, 0034]
With respect to claim 29-30, Hao discloses detecting the level of miRNA-155 comprises performing a nucleic acid amplification assay, quantitative PCR. [Hao, 0042, 0043]
Hao does not disclose a biological fluid sample is obtained.
With respect to claim 21, Newman discloses a method comprising:
a) identifying a patient diagnosed with a disease;
b) obtaining a biological fluid sample from the patient; and
c) collecting exosomes from the biological fluid sample. [Newman, 0197-0204]
With respect to claim 25-26, Newman discloses the exosomes may be collected by affinity capture using an immobilized antibody that specifically binds ALG6. [Newman, 0059-0065, 0204-0206]
With respect to claim 27, Newman discloses the exosomes may be collected by affinity capture using a lectin immobilized on a solid substrate. [Newman, 0059-0060]
With respect to claim 28, Newman discloses the lectin is Galanthus nivalis lectin (GNA). [Newman, 0059-0060]
Modifying the method disclose by Hao by obtaining a biological fluid sample from the patient, rather than a tissue sample, results in the method of claim 21.
Modifying the method disclose by Hao by collecting the exosomes by immunoaffinity capture using an immobilized antibody that specifically binds ALG6 results in the method of claim 25 and 26.
Modifying the method disclose by Hao by collecting the exosomes by immunoaffinity capture using a lectin, GNA, immobilized on a solid substrate, results in the method of claim 27 and 28.
It would be obvious to one of ordinary skill in the art to modify the method disclose by Hao by obtaining a fluid sample from the patient, rather than a tissue sample, and have a reasonable expectation of success. Hao discloses a method comprising collecting exosomes from a tissue sample obtained from a patient diagnosed with a disease. Newman discloses a method comprising collecting exosomes from a fluid sample. Thus, Newman establishes that a fluid sample is an acceptable biological sample for exosome collection. Accordingly, the combined teachings of Hao and Newman suggest that in the method disclosed by Hao, the exosomes may be collected from a fluid sample obtained from the patient. Therefore, it is reasonable to expect the method disclosed by Hao may be modified by obtaining a fluid sample from the patient. One would have been motivated to do so because substituting equivalent exosome sources known for the same purpose when the equivalency must be recognized in the prior art, is prima facie obvious. MPEP 2144.06(II). In the present case, Newman discloses bodily fluids and tissues are exosome sources, from which exosomes may be collected via immunoaffinity capture. [Newman, 0206] Therefore, substituting one known exosome source (bodily tissues) in the method disclosed by Hao, for another (bodily fluid), is prima facie obvious.
It would be obvious to modify the method disclose by Hao by collecting the exosomes via immunoaffinity capture using an immobilized antibody that specifically binds ALG6 or using a lectin, GNA, immobilized on a solid substrate and have a reasonable expectation of success. Hao discloses a method comprising collecting exosomes from a biological sample obtained from a patient diagnosed with a disease. Newman discloses a method comprising collecting exosomes from a biological sample obtained from a patient diagnosed with a disease via immunoaffinity capture using an immobilized antibody that specifically binds ALG6 or using a lectin, such as GNA, immobilized on a solid substrate. Thus, Newman establishes that collecting exosomes via immunoaffinity capture using an immobilized antibody that specifically binds ALG6 or using GNA immobilized on a solid substrate are well-established techniques in the art. Accordingly, the combined teachings of Hao and Newman suggest that in the method disclosed by Hao, the exosomes may be collected via immunoaffinity capture using an immobilized antibody that specifically binds ALG6 or using GNA immobilized on a solid substrate. Therefore, it is reasonable to expect the method disclose by Hao may be modified by collecting the exosomes via immunoaffinity capture using an immobilized antibody that specifically binds ALG6 or using GNA immobilized on a solid substrate. One would have been motivated to do so because substituting equivalent methodologies known for the same purpose when the equivalency must be recognized in the prior art, is prima facie obvious. MPEP 2144.06(II). In the present case, Newman discloses exosomes may be collected by a variety of methodologies, including but not limited to affinity capture and ultracentrifugation. Therefore, substituting one known methodology for collecting exosomes (ultracentrifugation) in the method disclosed by Hao, for another (immunoaffinity capture) is prima facie obvious.
Response to Arguments
Applicant’s arguments, filed 2/16/2026, with respect to claims 1-20 have been considered but are moot because Applicant has cancelled claims 1-20 and the new ground of rejection over claims 21-31 does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
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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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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