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 .
Claim Status
Applicant’s submission filed 03/26/2026 has been received and entered. Claims 4 and 16 have been cancelled. Claims 1, 10, 21 and 22 have been amended. Claims 44 and 45 have been new added. Accordingly, claims 1-3, 7-8, 10-12, 14, 17, 20-22, 24, 26-27 and 42-45 are pending and under current examination.
Status of Prior Rejections/Response to Arguments
The objection to Abstract is withdrawn:
The objection to the abstract of the disclosure have been withdrawn due to applicant’s amendment to the abstract and submitted as a single paragraph on a separate sheet as required.
The objection to Drawing is withdrawn:
Applicant's submission of replacement sheets is effective to obviate the current objection on record. The objection is withdrawn.
The objection to claims 21 -22 is withdrawn:
Applicant’s amendment to claims 21-22 adds the full name of the abbreviation “EQ-5D” is effective to obviate the current objection on record. The objection is withdrawn.
The rejection to claims 1-3, 7-8, 10-12, 14, 16-17, 20-22, 24, 26-27 and 42-43 under 35 U.S.C. § 112(b) is withdrawn:
The cancellation of claim 16 renders the rejection thereto moot.
Applicant’s amendment to claim 1 replaces “the subject” in line 2 with “a subject”, to claim 10 changes it’s dependency to depend from claim 8, to claim 21 spells out the full name of “EQ-5D” as EuroQol-5 Dimension which is not a trademark/trade name, is effective to obviate the current rejection on record. The rejection is withdrawn.
The rejection to claims 1, 3, 7-8, 10-12, 14, 17, 24, 26, 27, 42 and 43 under 35 U.S.C. § 102(a)(1) and (a)(2) over Riordan, as evidenced by Kalso et al. is withdrawn in part:
Regarding claims 1, 3, 7-8, 10-12, 14, 17, 24, 26 and 27, Applicant’s amendment to claim 1 adds the limitation “ (the subject) has been using an opioid for at least 1 to 6 months prior to administering the composition”. Riordan do not teach this limitation. Therefore the amendment obviates the current rejection on record. The rejection is withdrawn.
Regarding claims 42 and 43, since there is no amendment to said claims, Riordan still anticipates the method in the claims. The rejection is maintained.
The rejection to claim 4 under 35 U.S.C. § 102(a)(1) over Amirdelfan is withdrawn:
The cancellation of claim 4 renders the rejection thereto moot. The rejection is withdrawn.
The rejection to claims 1, 3, 7, 20, 42 and 43 under 35 U.S.C. § 102(a)(1) and (a)(2) over Qu et al. is withdrawn in part:
Regarding claims 1, 3, 7 and 20, Applicant’s amendment to claim 1 adds the limitation “ (the subject) has been using an opioid for at least 1 to 6 months prior to administering the composition”. Qu et al. do not teach this limitation. Therefore the amendment obviates the current rejection on record. The rejection is withdrawn.
Regarding claims 42 and 43, since there is no amendment to said claims 42, Qu still anticipates the method in the claims. The rejection is maintained.
Regarding Applicant’s argument: Applicant has traversed the rejection, asserting the amended claims now clearly require that there is a reduction in actual opioid use, which is distinct to attenuated opioid tolerance as shown in Qu. Qu does not show a reduction in opioid use at all; only a reduction in opioid tolerance was observed (Remarks, p11). In response, the Examiner submits that the preambles “(a method of) reducing opioid use”(claim 42) and “(a method of) reducing pain or reducing opioid use or increasing EQ-5D score” (claim 43) only states 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. In instant case, Qu et al. teach the same method of administering mesenchymal stem cells into a subject before or during the course of opioid treatment (see parag 0008), therefore still anticipate instant claims 42 and 43.
The rejection to claims 1-3, 7-8, 10-12, 14, 17, 21, 22, 24, 26, 27, 42 and 43 under 35 U.S.C. § 103 over Riordan, evidenced by Kalso et al., in view of Amirdelfan et al., as evidenced by Whynes et al. is maintained:
The rejection to claims 1, 3, 7-8, 10-12, 14, 16, 17, 24, 26, 27, 42 and 43 under 35 U.S.C. § 103 over Riordan, evidenced by Kalso et al., in view of GlobeNewswire is maintained:
The cancellation of claim 4 renders the rejection thereto moot.
Applicant has amended claim 1 and traversed the rejection, asserting that Riordan is not at all focused on opioids, and the only mention of the opioid oxycodone is within the Examples for providing background information of a single patient. The entire focus of Riordan is on the reduction of pain (Remarks, p14). Riordan does not provide any suggestion to arrive at the presently claimed methods. Riordan does not provide a reasonable expectation of success for a POSITA to practice a method of reducing opioid use comprising administration of compositions comprising MLPSCs in subjects that have been using an opioid for at least 1 to 6 months prior to administering the composition, as claimed (Remarks, p14).
Applicant’s arguments are fully considered but they are not persuasive. As stated in “claim interpretation” part of the office action mailed 11/26/2025, the preambles such as “(a method of) reducing opioid use” or “(a method of) reducing pain or reducing opioid use or increasing EQ-5D score” only states 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. Moreover, MPEP 2123.I states "[T]he use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). In instant case, 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), which reads on the active step “administering to a subject a composition comprising mesenchymal lineage precursor or stem cells (MLPSCs)” of the claimed method. Riordan also teaches in the Example that a subject which had been using an opioid for an undisclosed period of time stopped using opioid after the administration of MSCs. Therefore PHOSITA would have been taught or apprised by the teaching, and selected subjects who had been using an opioid prior to the administration of MSCs, and confirmed whether the administration of MSCs would discontinue or reduce the use of opioids, with a reasonable expectation that the subjects would have at least decreased the use of opioid.
Applicant has further traversed the rejection, asserting that GlobeNewswire is silent regarding the patients' opioid use prior to treatment, much less the specific period of at least 1 to 6 months (Remarks, p15). In response, the Examiner submits that GlobeNewswire teaches the “reduced use” of opioid by administering MPC in the result part (p2, parag 1), which indicates that the subjects are necessarily using opioid prior to the clinical trial for a period of time (which is long enough that the data of using the opioid can be collected and compared). GlobeNewswire also teaches the enrolled patients having moderate to severe low back pain persisting for more than 6 months, indicates the subjects in the clinical trial include patients who have used an opioid to reduce pain (including severe pain), for a period spanning 6 months prior to administering the MPC composition. It is Applicant’s burden to explain how it would be patentably distinct between instant invention and GlobeNewswire’s method of administering to the subjects mesenchymal precursor cells (MPCs). The rejection is maintained in modified form to address the new limitations.
New/Modified Rejections
Claim Interpretation
Claim 1 recites a preamble “(a method of) reducing opioid use”, 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 1 recites “whereby after administering the composition the subject's opioid use is reduced”, given that MPEP § 2111.04 states “[a] whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited", this limitation is not considered a limitation to be given patentable weight.
Maintained 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 42 and 43 stand 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 claims 42 and 43, 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 claims. 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.
Claims 42 and 43 stand 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 claims 42 and 43, 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.
Modified 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, 24, 26, 27 and 42-43 stand rejected and claims 44 and 45 are newly rejected under 35 U.S.C. 103 as being unpatentable over Riordan (US 2018/0036348 A1, published in 2018, cited in IDS) in view of GlobeNewswire (January 29, 2014), as evidenced by Kalso et al. (J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56). The rejection is necessitated by Applicant’s amendment.
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). Riordan does 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 1, GlobeNewswire teaches the “reduced use” of opioid by administering MPC (p2, parag 1), indicates that the subjects are inherently using opioid prior to the clinical trial for a period of time which is long enough that the data of using the opioid can be collected and compared). GlobeNewswire also teaches the enrolled patients having moderate to severe low back pain persisting for more than 6 months (p1, parag 1), indicates the subjects in the clinical trial most likely including patients who have used an opioid for at least 1 month (i.e., 1-6 months) or similar period of time 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 a period of time (i.e., 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 administering MPCs to patients with moderate to severe low back pain persisting for more than 6 months (p1, parag 1), and results in “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 that has been using an opioid for a period of time (i.e., 1 to 6 months or so prior to administering the composition) for the MSCs administration depends on their research preference or interest (i.e., to study the effect of MSCs administration on the subjects with opioids use). This simple substitution of one known element (administering MSCs to a subject who has been using an opioid for at least 1 to 6 months prior to administering the composition) for another known element (administering MSCs to a subject who has been using an opioid for a period of time) 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 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 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.
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.
Regarding claim 44, , 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). MSC can be derived from any tissue including, but not limited to, bone marrow, adipose tissue, amniotic fluid, endometrium, trophoblast - derived tissues, cord blood, Wharton jelly, placenta, amniotic tissue, derived from pluripotent stem cells, and tooth (parag 0029). This teaching reads on the bone marrow-derived mesenchymal lineage precursor or stem cells (MLPSCs) as recited in instant claim.
Regarding claim 45, GlobeNewswire teaches 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).
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 (i.e., bone marrow-derived MSCs) to reduce pain, and use allogeneic mesenchymal precursor cells as taught by GlobeNewswire. The only difference between instant claim and Riordan’s method is instant claim use bone marrow-derived allogeneic mesenchymal precursor cells (MPCs). Given that GlobeNewswire teaches using allogeneic MPCs for administration, one of ordinary skill in the art would have substituted Riordan’s method of administering MSCs (i.e., bone marrow derived MSCs), and use bone marrow-derived allogeneic mesenchymal precursor cells (MPCs) for the administration depends on their research preference or interest. This simple substitution of one known element (use bone marrow-derived allogeneic MPCs for administration) for another known element (use bone marrow-derived MSCs for administration) 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.).
Claims 1-3, 7-8, 10-12, 14, 17, 21, 22, 24, 26, 27 and 42-43 stand rejected and claims 44-45 are newly rejected under 35 U.S.C. 103 as being unpatentable over Riordan (US 2018/0036348 A1, published in 2018, cited in IDS) in view of GlobeNewswire (January 29, 2014), as evidenced by Kalso et al. (J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56), as applied to 1, 3, 7-8, 10-12, 14, 17, 24, 26, 27 and 42-45 above, further 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). The rejection is necessitated by Applicant’s amendment.
The teaching of Riordan and GlobeNewswire is set forth above.
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, 17, 24, 26, 27 and 42-43 stand rejected and claims 20, 44 and 45 are newly rejected under 35 U.S.C. 103 as being unpatentable over Riordan (US 2018/0036348 A1, published in 2018, cited in IDS) in view of GlobeNewswire (January 29, 2014), as evidenced by Kalso et al. (J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56), as applied to 1, 3, 7-8, 10-12, 14, 17, 24, 26, 27 and 42-45 above, further in view of Deyo et al. (BMJ. 2015 Jan 5;350:g6380). The rejection is necessitated by Applicant’s amendment.
The teaching of Riordan and GlobeNewswire is set forth above.
Regarding claim 20, Riordan and GlobeNewswire do not teach the opioid is morphine. However, this was disclosed by Deyo et al. at the time of instant invention.
Deyo et al. examine trends and variations in the use of opioids for back pain; assess the evidence for opioid efficacy in acute and chronic back pain; summarize new data on the adverse effects of long term opioids; and make recommendations for judicious prescribing (p1, left column).
Regarding claim 20, Deyo et al. teach opioids are mostly prescribed for chronic pain (p2, right column). Morphine is one of six powerful opioids (which including fentanyl, hydromorphone, methadone, morphine, oxycodone, and pethidine (meperidine), see p2, figure 1).
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 in view of GlobeNewswire’s method of administering mesenchymal stem cells to a subject to reduce pain, wherein the subject was having morphine to reduce pain, as taught by Deyo et al.. The only difference between instant claim and Riordan in view of GlobeNewswire’s method of administering mesenchymal stem cells to a subject to reduce pain is instant claim has subject used morphine to reduce pain. Given that Deyo et al. teach morphine is one of six powerful opioids mostly prescribed for chronic pain, one of ordinary skill in the art would have substitute the subjects used morphine instead of oxycodone to test the effect of administering mesenchymal stem cells. This simple substitution of one known element (having subjects having morphine to reduce pain) for another known element (having subjects having oxycodone to reduce 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.
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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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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