DEATILED 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 .
Priority
The instant application is a national stage entry of PCT application PCT/US2022/013349, filed 07/21/2023 under 35 USC 371. Acknowledgement is made of the applicant’s claim for benefit to prior-filed U.S. provisional patent applications 63/298,391 (filed 01/11/2022), as well as for foreign priority based on an application AU2021900147 (with a filing date of 01/22/2021) and an application AU2021900250 (with a filing date of 02/04/2021) both filed in Australia.
Abstract
The abstract of the disclosure is objected to because the abstract has less than 50 words and does not clearly summarize the invention including the use of mesenchymal lineage precursor or stem cells (MLPSCs) in the invention. See MPEP 1826. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Drawings
The drawings filed 07/21/2023 are objected to because the letters and numbers in figures 1-2, 4-8, 10 and 19-34 are very blurry and difficult to reproduce. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 21 and 22 are objected to because of the following informalities: when the abbreviations “EQ-5D” and “ODI” are first time introduced in the claim, they should be accompanied by their full descriptions. 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.
Claims 1-3, 7-8, 10-12, 14, 16-17, 20-22, 24, 26-27 and 42-43 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 1 recites the limitation " the subject" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 2, 3, 7-8, 10-12, 14, 16-17, 20-22, 24, 26-27 and 42-43 depend from, at least, claim 1, and thus inherit the deficiency and are rejected on the same basis.
Claim 10, which depends upon claim 7, recites the limitation "the lower back pain" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 21 contains the trademark/trade name EQ-5D. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a questionnaire/measurement which regarding 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and, accordingly, the identification/description is indefinite.
Claim Interpretation
Claim 1 recites a preamble “(a method of) reducing opioid use”, claim 4 recites a preamble “opioid sparing”, claim 42 recites a preamble “(a method of) reducing pain”, claim 43 recites a preamble “(a method of) reducing pain or reducing opioid use or increasing EQ-5D score”, each preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation to be given patentable weight and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See MPEP 2111.02.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 7-8, 10-12, 14, 17, 24, 26, 27, 42 and 43 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Riordan (US 2018/0036348 A1, published in 2018, cited in IDS), as evidenced by Kalso et al. (J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56).
Riordan discloses means of treating pain through administration of mesenchymal stem cells or derivatives thereof via an intrathecal manner at a concentration and frequency sufficient to reduce pain (Abstract).
Regarding claim 1, Riordan teaches the use of intrathecally administered mesenchymal stem cells (MSCs) to reduce pain, in particular discogenic pain in the back of a patient (parag 0002). This teaching reads on a method comprising administering to a subject a composition comprising MSCs, which belong to the mesenchymal lineage precursor or stem cells (MLPSCs), as recited in instant claim. Furthermore, Riordan teaches an example (parag 0107-parag 0110) administering MSCs for the treatment to a patient suffering from lower back pain. Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110). Oxycodone is an opioid, as evidenced by Kalso et al. (see i.e., p s48, left column). This teaching reads on “the subject is using an opioid” as recited in instant claim. Therefore the teaching of Riordan anticipates instant claim.
Regarding claim 3, as discussed above, Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110), wherein oxycodone is an opioid, as evidenced by Kalso et al. (see i.e., p s48, left column).
Regarding claims 7 and 8, following the discussion above, Riordan teaches an example (parag 0107-parag 0110) administering MSCs for the treatment to a patient suffering from lower back pain. Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110). This teaching reads on “the pain is chronic pain” and “the pain is lower back pain” as recited in instant claims.
Regarding claims 10 and 11, following the discussion above, Riordan teaches the invention teaches use of intrathecally administered mesenchymal stem cells in reduction and / or amelioration of back pain, or other types of pain (parag 0007). Degenerative Disc Disease is one of the diseases cause back pain. In some embodiments, the degenerative disc disease can include an intervertebral disc herniation. As used herein “intervertebral disc herniation” includes local displacement of disc material beyond the limits of the intervertebral disc space. The disc material may be nucleus pulposus, cartilage , fragmented apophysical bone, annular tissue or any combination thereof. Displacement of disc material may put pressure on the exiting spinal nerve and/or cause an inflammatory reaction leading to radiculopathy, weakness, numbness, and / or tingling in the arms or legs. This teaching reads on the lower back pain is associated with inflammation in an intervertebral disc (as recited in instant claim 10) and the nerve inflammation is in the i.e., nucleus pulposus (as recited in instant claim 11).
Regarding claims 12, Riordan discloses an example that right after administering MSCs, the use of opioid (oxycodone) is discontinued, but do not specifically point out opioid use can be reduced reduced between 1 and 3 months after administration of the composition. However, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02. Moreover, this result can be evidenced by GlobeNewswire. GlobeNewswire discloses a positive 12-month outcome results from the 100-patient Phase 2 clinical trial of its proprietary allogeneic, or "off-the-shelf", Mesenchymal Precursor Cells (MPCs) in patients with chronic moderate to severe discogenic low back pain (p1, parag 1). Regarding instant claim, GlobeNewswire teaches the data of the reduction of pain, reduced opioids use at the 12-month time point. These teachings show that the effect of MSCs administration appears in a range of period from short time after MSCs administration (i.e., right after MSCs administration) to 12 months, which indicates that opioid use can be reduced around 1 month to 3 months after administration of the composition, as recited in instant claim.
Regarding claim 14, Riordan teach an example that right after administering MSCs, the use of opioid (oxycodone) is discontinued, indicates the effect of MSCs is fast (i.e., right after MSCs administration). GlobeNewswire teaches the clinical trial using MPCs reduced opioid use for pain relief: At 12 months, mean daily use of opioid medications for back pain was reduced by as much as 42% (that is, 0-42%) in the 18M MPC group compared with the saline control group (p2, parag 1). These teachings read on the opioid use is reduced for at least 12 months after administration of the composition, as recited in instant claim. Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 17, GlobeNewswire teaches Mesenchymal Precursor Cells (MPCs) reduced opioid use for pain relief: At 12 months, mean daily use of opioid medications for back pain was reduced by as much as 42% (that is, 0-42%) in the 18M MPC group compared with the saline control group (p equals 0.17) (p2, parag 1). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 24, GlobeNewswire teaches the clinic trial have improvement in chronic low back pain, such as reduction in mean pain score, some patients achieving greater than 50% reduction in pain score (p1, improvement (a), (b)), this teaching indicates that some population which has huge pain reduction can discontinues opioid use at 12 months after administration of the composition, as recited in instant claim. Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 26, following the discussion above, Riordan teaches the “MSC ” may include cells that are isolated from tissues using cell surface markers selected from the list comprised of NGF-R, PDGF-R, EGF-R, IGF-R, CD29, CD49a, CD56, CD63, CD73, CD105, CD106, CD140b, CD146, CD271, MSCA-1, SSEA4, STRO-1 and STRO-3 or any combination thereof, and satisfy the ISCT criteria either before or after expansion (parag 0029). This teaching indicates isolating the STRO-1+ from tissue and (culture in vitro) for expansion, reads on the MSCs are culture expanded from a population of stem cells which comprises STRO-1+ cells as recited in instant claim.
Regarding claim 27, as discussed above, Riordan teaches the use of intrathecally administered mesenchymal stem cells to reduce pain, in particular discogenic pain in the back of a patient (parag 0002), this teaching reads on that the MLPSCs are mesenchymal stem cells (MSCs).
Regarding claims 42 and 43, following the discussion of claim 1, Riordan teaches the use of intrathecally administered mesenchymal stem cells to reduce pain , in particular discogenic pain in the back of a patient (parag 0002). This teaching reads on a method comprising administering to a subject a composition comprising MSCs, which belong to the mesenchymal lineage precursor or stem cells (MLPSCs), as recited in instant claim. Furthermore, Riordan teaches an example (parag 0107-parag 0110) administering MSCs for the treatment to a patient suffering from lower back pain. Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110). Oxycodone is an opioid, as evidenced by Kalso et al. (see i.e., p s48, left column). This teaching reads on “the subject is using an opioid” as recited in instant claim. Therefore the teaching of Riordan anticipates instant claims.
Claim 4 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Amirdelfan et al. (Spine J. 2021 Feb;21(2):212-230., available online 9 October 2020, cited in IDS).
Amirdelfan et al. evaluate the safety and efficacy of a single intradiscal injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with moderate degenerative disc disease (DDD) through 36-month follow-up (p214, left column).
Regarding claim 4, Amirdelfan et al. teach in their study, subjects were randomized into one of four groups: (1) approximately 6 million allogeneic MPCs in 1% HA; (2) approximately 18.0 million allogeneic MPCs in 1% HA; (3) 1% HA (vehicle control); and (4) sterile saline (placebo control). Herein the groups (1) and (2) with MPCs in 1% HA reads on the composition comprising mesenchymal precursor cells (MPCs) and 1% hyaluronic acid (HA) as recited in instant claim.
Claims 1, 3, 7, 20, 42 and 43 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Qu et al. (US 2015/0246074 A1, published in 2018, cited in IDS).
Qu et al. teach methods of reducing pain and/or preventing or reducing opioid tolerance in a subject by administering to the subject mesenchymal stem cells (Abstract).
Regarding claim 1, Qu et al. teach a method of attenuating opioid tolerance in a subject comprising administering a number of mesenchymal stem cells effective to attenuate opioid tolerance into the subject before or during the course of opioid treatment (parag 0008). This teaching anticipates the method comprising administering to the subject a composition comprising mesenchymal stem cells (which is one type of mesenchymal lineage precursor or stem cells (MLPSCs)), wherein the subject is using an opioid, as recited in instant claim.
Regarding claim 3, following the discussion above, Qu et al. teach opioids can be efficacious in the treatment of pain, however, the development of opioid tolerance over time can limit opioid effectiveness, compromise safety, and lead to detrimental consequences, including drug overdose, abuse, and addiction (parag 0005). Qu et al. also teach methods of reducing pain and/or preventing or reducing opioid tolerance in a subject by administering to the subject mesenchymal stem cells. This teaching reads on the subject is using an opioid for pain.
Regarding claim 7, following the discussion above, Qu et al. teach transplantation of MSCs, particularly autologous MSCs obtained from the bone marrow of the patient, to treat chronic pain and opioid tolerance is an innovative and practical approach (parag 0025). This teaching reads on the pain is chronic pain.
Regarding claim 20, Qu et al. teach a method of attenuating opioid tolerance in a subject comprising administering a number of mesenchymal stem cells effective to attenuate opioid tolerance into the subject before or during the course of opioid treatment (parag 0010), in an embodiment, the opioid is morphine (parag 0015).
Regarding claims 42 and 43, following the discussion above, Qu et al. teach a method of attenuating opioid tolerance in a subject comprising administering a number of mesenchymal stem cells effective to attenuate opioid tolerance into the subject before or during the course of opioid treatment (parag 0008). This teaching anticipates the method comprising administering to the subject a composition comprising mesenchymal stem cells (which is one type of mesenchymal lineage precursor or stem cells (MLPSCs)), wherein the subject is using an opioid, as recited in instant claims.
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 (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 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, 7-8, 10-12, 14, 17, 21, 22, 24, 26, 27, 42 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Riordan (US 2018/0036348 A1, published in 2018, cited in IDS), as evidenced by Kalso et al. (J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56), in view of Amirdelfan et al. (Spine J. 2021 Feb;21(2):212-230., available online 9 October 2020, cited in IDS), as evidenced by Whynes et al. (Health Qual Life Outcomes. 2008 Nov 7;6:94).
Riordan discloses means of treating pain through administration of mesenchymal stem cells or derivatives thereof via an intrathecal manner at a concentration and frequency sufficient to reduce pain (Abstract).
Regarding claim 1, Riordan teaches the use of intrathecally administered mesenchymal stem cells (MSCs) to reduce pain, in particular discogenic pain in the back of a patient (parag 0002). This teaching reads on a method comprising administering to a subject a composition comprising MSCs, which belong to the mesenchymal lineage precursor or stem cells (MLPSCs), as recited in instant claim. Furthermore, Riordan teaches an example (parag 0107-parag 0110) administering MSCs for the treatment to a patient suffering from lower back pain. Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110). Oxycodone is an opioid, as evidenced by Kalso et al. (see i.e., p s48, left column). This teaching reads on “the subject is using an opioid” as recited in instant claim.
Regarding claim 3, as discussed above, Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110), wherein oxycodone is an opioid, as evidenced by Kalso et al. (see i.e., p s48, left column).
Regarding claims 7 and 8, following the discussion above, Riordan teaches an example (parag 0107-parag 0110) administering MSCs for the treatment to a patient suffering from lower back pain. Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110). This teaching reads on “the pain is chronic pain” and “the pain is lower back pain” as recited in instant claims.
Regarding claims 10 and 11, following the discussion above, Riordan teaches the invention teaches use of intrathecally administered mesenchymal stem cells in reduction and / or amelioration of back pain, or other types of pain (parag 0007). Degenerative Disc Disease is one of the diseases cause back pain. In some embodiments, the degenerative disc disease can include an intervertebral disc herniation. As used herein “intervertebral disc herniation” includes local displacement of disc material beyond the limits of the intervertebral disc space. The disc material may be nucleus pulposus, cartilage , fragmented apophysical bone, annular tissue or any combination thereof. Displacement of disc material may put pressure on the exiting spinal nerve and/or cause an inflammatory reaction leading to radiculopathy, weakness, numbness, and / or tingling in the arms or legs. This teaching reads on the lower back pain is associated with inflammation in an intervertebral disc (as recited in instant claim 10) and the nerve inflammation is in the i.e., nucleus pulposus (as recited in instant claim 11).
Regarding claims 12, Riordan teaches an example that right after administering MSCs, the use of opioid (oxycodone) is discontinued, but do not specifically point out opioid use is reduced between 1 and 3 months after administration of the composition. However, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02. Moreover, this result can be evidenced by GlobeNewswire. GlobeNewswire discloses a positive 12-month outcome results from the 100-patient Phase 2 clinical trial of its proprietary allogeneic, or "off-the-shelf", Mesenchymal Precursor Cells (MPCs) in patients with chronic moderate to severe discogenic low back pain (p1, parag 1). Regarding instant claim, GlobeNewswire teaches the data of the reduction of pain, reduced opioids use at the 12-month time point. These teachings show that the effect of MSCs administration appears in a range of period from short time after MSCs administration (i.e., right after MSCs administration) to 12 months, which indicates that opioid use can be reduced around 1 month to 3 months after administration of the composition, as recited in instant claim.
Regarding claim 14, Riordan teach an example that right after administering MSCs, the use of opioid (oxycodone) is discontinued, indicates the effect of MSCs is fast (i.e., right after MSCs administration). GlobeNewswire teaches the clinical trial using MPCs reduced opioid use for pain relief: At 12 months, mean daily use of opioid medications for back pain was reduced by as much as 42% (that is, 0-42%) in the 18M MPC group compared with the saline control group (p2, parag 1). These teachings read on the opioid use is reduced for at least 12 months after administration of the composition, as recited in instant claim. Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 17, GlobeNewswire teaches Mesenchymal Precursor Cells (MPCs) reduced opioid use for pain relief: At 12 months, mean daily use of opioid medications for back pain was reduced by as much as 42% (that is, 0-42%) in the 18M MPC group compared with the saline control group (p equals 0.17) (p2, parag 1). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 24, GlobeNewswire teaches the clinic trial have improvement in chronic low back pain, such as reduction in mean pain score, some patients achieving greater than 50% reduction in pain score (p1, improvement (a), (b)), this teaching indicates that some population which has huge pain reduction can discontinues opioid use at 12 months after administration of the composition, as recited in instant claim. Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 26, following the discussion above, Riordan teaches the “MSC ” may include cells that are isolated from tissues using cell surface markers selected from the list comprised of NGF-R, PDGF-R, EGF-R, IGF-R, CD29, CD49a, CD56, CD63, CD73, CD105, CD106, CD140b, CD146, CD271, MSCA-1, SSEA4, STRO-1 and STRO-3 or any combination thereof, and satisfy the ISCT criteria either before or after expansion (parag 0029). This teaching indicates isolating the STRO-1+ from tissue and (culture in vitro) for expansion, reads on the MSCs are culture expanded from a population of stem cells which comprises STRO-1+ cells as recited in instant claim.
Regarding claim 27, as discussed above, Riordan teaches the use of intrathecally administered mesenchymal stem cells to reduce pain, in particular discogenic pain in the back of a patient (parag 0002), this teaching reads on that the MLPSCs are mesenchymal stem cells (MSCs).
Regarding claims 42 and 43, following the discussion of claim 1, Riordan teaches the use of intrathecally administered mesenchymal stem cells to reduce pain , in particular discogenic pain in the back of a patient (parag 0002). This teaching reads on a method comprising administering to a subject a composition comprising MSCs, which belong to the mesenchymal lineage precursor or stem cells (MLPSCs), as recited in instant claim. Furthermore, Riordan teaches an example (parag 0107-parag 0110) administering MSCs for the treatment to a patient suffering from lower back pain. Riordan teaches before treatment the patient used to take Lyrica, oxycodone at all times due to extreme chronic pain (parag 0110). Oxycodone is an opioid, as evidenced by Kalso et al. (see i.e., p s48, left column). This teaching reads on “the subject is using an opioid” as recited in instant claim.
Regarding claim 2, Riordan does not teach the composition comprises hyaluronic acid (HA). However, this was disclosed by Amirdelfan et al. at the time of instant invention.
Amirdelfan et al. evaluate the safety and efficacy of a single intradiscal injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with moderate degenerative disc disease (DDD) through 36-month follow-up (p214, left column).
Regarding claim 2, Amirdelfan et al. teach in their study, subjects were randomized into one of four groups: (1) approximately 6 million allogeneic MPCs in 1% HA; (2) approximately 18.0 million allogeneic MPCs in 1% HA; (3) 1% HA (vehicle control); and (4) sterile saline (placebo control). Herein the groups (1) and (2) with MPCs in 1% HA reads on the composition comprising mesenchymal precursor cells (MPCs) and 1% hyaluronic acid (HA).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Riordan’s method of administering mesenchymal stem cells to reduce pain, and use 1% hyaluronic acid (HA) as a carrier for the administration of MSCs, as taught by Amirdelfan et al.. The only difference between instant claim and Riordan’s method is instant claim using the composition comprising MSCs and 1% HA for the administration. Given that Amirdelfan et al. teach successfully using MPCs with 1% hyaluronic acid carrier for injection into the target disk, one of ordinary skill in the art would have substituted Riordan’s method of administering MSCs, and use 1% HA carrier with the MSCs for the administration depends on their research preference. This simple substitution of one known element (administering 1% HA carrier with the MSCs for the treatment of back pain) for another known element (administering MSCs for the treatment of back pain) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 21, Amirdelfan et al. teach Visual analog scale (VAS) pain score was used as the primary determination of pain reduction in the study (p220, left column). The VAS is part of EQ-5D as evidenced by Whynes et al. (see, i.e., Abstract). Amirdelfan et al. teach lower back pain VAS scores which increase in all groups including MPCs groups (p219, table 3), and conducted a minimal pain responder analysis to evaluate the VAS and found Six and 18 million MPC showed significant improvement compared with saline at 12 months (p221, right column, and figure 6). This teaching reads on the increased score of EQ-5D as recited in instant claim. Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Regarding claim 22, Amirdelfan et al. teach Oswestry Disability Index (ODI) scores in four groups: sterile saline (placebo control) group, 1% HA (vehicle control) group, the group having approximately 6 million allogeneic MPCs in 1% HA, and the group having approximately 18.0 million allogeneic MPCs in 1% HA. The MPCs groups having a ODI 10 point function response in 30 days, 3 months, 6 months, 12 months, 24 months and 36 months (table 5, figure 7), reads on the limitation “the subject achieves a ODI 10 point function response” as recited in instant claim. Moreover, it is inherent property that same method using same product would having same effect. [w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). MPEP 2112.02.
Claims 1, 3, 7-8, 10-12, 14, 16, 17, 24, 26, 27, 42 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Riordan (US 2018/0036348 A1, published in 2018, cited in IDS), as evidenced by Kalso et al. (J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56), in view of the GlobeNewswire (January 29, 2014).
The teaching of Riordan is set forth above.
Regarding claim 16, Riordan do not teach the subject has been using an opioid for at least 1 to 6 months prior to administering the composition. However, this was disclosed by GlobeNewswire.
GlobeNewswire discloses a positive 12-month outcome results from the 100-patient Phase 2 clinical trial of its proprietary allogeneic, or "off-the-shelf", Mesenchymal Precursor Cells (MPCs) in patients with chronic moderate to severe discogenic low back pain (p1, parag 1).
Regarding claim 16, GlobeNewswire teaches Mesoblast's Phase 2 clinical trial enrolled 100 patients with moderate to severe low back pain persisting for more than 6 months (p1, parag 1), and also teach the result/improvement including the reduced use of opioid (p1-2), indicates that the subjects including some patients who have been using an opioid for at least 1 to 6 months prior to administering the MPC composition.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Riordan’s method of administering mesenchymal stem cells to reduce pain, and have a subject has been using an opioid for at least 1 to 6 months prior to administering the composition, as taught by GlobeNewswire. The only difference between instant claim and Riordan’s method is instant claim has a subject has been using an opioid for at least 1 to 6 months prior to administering the composition. Given that GlobeNewswire teaches patients with moderate to severe low back pain persisting for more than 6 months (p1, parag 1), and also teaches the result/improvement including the reduced use of opioid (p1-2), one of ordinary skill in the art would have substituted Riordan’s method of administering MSCs, and enroll a subject has been using an opioid for at least 1 to 6 months prior to administering the composition depends on their research preference or interest (i.e., see the effect of MSCs administration on the subjects with long-term opioids use). This simple substitution of one known element (having a subject has been using an opioid for at least 1 to 6 months prior to administering the composition who has back pain) for another known element (having a subject using an opioid who has back pain) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699