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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 18, 2025, has been entered.
DETAILED ACTION
The claims filed on December 18, 2025, have been acknowledged. Claims 1-32 were cancelled. Claim 33 has been amended. Claims 33-38 are pending and examined on the merits.
Priority
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d).The applicant claims foreign priority from JP2020-001657 filed on January 8, 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, received July 1, 2022. While a certified copy of the foreign patent application JP2020-001657 is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Information Disclosure Statement
The information disclosure statement (IDS) filed on November 17, 2025, has been considered.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 33-34 and 37-38 under 35 U.S.C. 102(a)(1) as being anticipated by Bhasin et al. (Cerebrovasc Dis Extra 6:107–119. 2016; identified in IDS) is withdrawn in light of Applicant’s amendments to claim 33 to recite that the physical exercise is performed using an assistive movement.
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 33-34 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sasaki et al. (Physical Therapy 96: 1791–1798. 2016), as evidenced by United States Patent Application No. 20170253930 (Hatchwell). This is a new rejection made in response to Applicant’s amendments to claim 33.
As an initial matter, the term “bone marrow mononuclear cells” is broadly interpreted to encompass any cells that are considered bone marrow mononuclear cells, such as mesenchymal stem cells.
Sasaki teaches they generated a rat stroke model by inducing permanent middle cerebral artery occlusion (MCAO) through intraluminal vascular occlusion with a microfilament. Sasaki examined the effects of MSC intravenous infusion and exercise. Rat MSCs derived from adult bone marrow (i.e. bone marrow mononuclear cells) were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Treadmill running exercise was performed for 20 minutes every day after MCAO. Exercise started 1 day after MCAO (i.e. after MCAO and MSC infusion) at a speed of 3 m/min with a slope of 0 degrees for 1 week, and speed was increased by 3 m/min every week until histological evaluation. The present study demonstrated that combined therapy of daily rehabilitation and intravenous infusion of MSCs 6 hours after permanent MCAO in the rat resulted greater reduction in infarction volume, improvement in behavioral performance, and facilitation of synaptogenesis compared with either MSC or rehabilitation alone (whole document).
Regarding the limitation, “wherein the physical exercise promotes bidirectional feedback between central and peripheral nerves”, it is recognized the exercises (such as running on a treadmill) used in the study would involve communication between central and peripheral nerves, promoting communication between the two. Furthermore, as can be seen in Figure 4, the limb placement test showed improvements at day 14 and 35, suggesting improved communication between central and peripheral nerves.
Regarding the limitation, “the physical exercise is performed using an assistive movement”, Hatchwell evidences that treadmills are considered assistive equipment (paragraph 0225). Therefore, running the rats on a treadmill is considered to fall within the limitation “using an assistive movement”.
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.
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 33-35 and 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Bhasin et al. (Cerebrovasc Dis Extra 6:107–119. 2016), and further in view of Takeuchi et al. (Front. Hum. Neurosci. 9: 1-15. 2015) and Kawase et al (J. Neural Eng. 14: 1-12. 2017). This is a new rejection made in response to Applicant’s amendments to claim 33 that is substantially similar to a previous rejection of record. Any aspect of Applicant’s traversal that is relevant to the rejection as newly written is addressed below.
Regarding claims 33-34, Bhasin teaches they administered autologous bone-marrow mononuclear stem cells to twenty stroke patients through intravenous infusion and administered a neuromotor rehabilitation regime for 8 weeks. Bhasin teaches that the rehabilitation exercises were motor imagery training using Xbox and mirror therapy were administered to the affected upper limb with bilateral hands focusing on principles of learning. Small hand muscle exercises like ball squeezing, lifting an object, rolling a cylindrical shape, and thrust release (mass finger extension) were included in the protocol. General aerobic exercise training was administered with 10 min of static cycling and brisk walk (the extent the patient can), partial squats (hold for 7 s), and step up and down. Patients diagnosed with ischemic stroke 3 months to 1.5 years after the index event with Medical Research Council (MRC) grade of power for wrist and hand muscles of at least 2, Brunnstrom stage of recovery of 2–5, National Institutes of Health Stroke Scale (NIHSS) score of between 4 and 15 (i.e. sequela of cerebral infarction) were recruited (abstract and page 109, paragraph 1-page 10, paragraph 2). Bhasin teaches that patients showed a statistically significant increase (baseline to 8 weeks) in BDNF (i.e. an effect of exercise). Serum BDNF levels rise during exercise. The activity-dependent secretion is crucial to the role of BDNF in promoting neuroplasticity in circuits activated in response to enrichened experience, i.e., stem cells along with exercise (page 115, paragraphs 3-4).
Regarding the limitation, “wherein the physical exercise promotes bidirectional feedback between central and peripheral nerves”, it is recognized the exercises (such as ball squeezing) used in the study would involve communication between central and peripheral nerves, promoting communication between the two.
Bhasin does not teach wherein exercise is performed using an assistive movement/an assistive movement device.
However, Takeuchi teaches that muscle activity-dependent stimulation is not applicable for the stroke patients with severe hemiparesis who have no voluntary muscle activation. Therefore, these patients require activity-dependent stimulation paradigms based on brain activity. It is postulated that the re-establishment of the disrupted sensorimotor loop by integrating movement intention and passive limb movement, assisted by a robot, will strengthen the associative connection (page 7, paragraph 2).
Kawase teaches a hybrid brain-machine interface exoskeleton for use in patients with paresis by combining EMG and EEG signals to control arm and hand movements, respectively
The hybrid BMI-based exoskeleton (BOTAS, as seen in figure 1; an assistive movement device) for paresis consists of an EEG-based controller (a voluntary control unit for neurotransmissions) for joints with no or little residual muscle activity, and an EMG-based controller (a voluntary control unit for muscle potential) for other joints with residual muscle activity. We used the BOTAS, which is an exoskeleton with six degrees of freedom to assist the whole arm and fingers (figure 1(a), bottom). In our previous study, sensorimotor rhythm, P300, and SSVEP (biological signals) were used to drive the exoskeleton for reaching and grasping movements (figure 1(a), left). The system allows users to trigger a registered motion of joints with no or little residual muscle activity by measuring EEG signals (uses sensors to measure EEG signal as seen in Figure 1a), processing them to identify the motion that will be performed (a processing unit), and using the EEG-based controller. They also implemented a new real-time control system based on estimation of joint angles using EMG signals measured by electrodes (a sensor) (figure 1(a), right). The new system enables users to control joints that utilize residual muscle activity. The EMG signal were processed (a processing unit) and used to estimate the flexion/extension angles of the elbow, wrist, and MP joint of the index finger (page 2, column 2, paragraph 3-page 6, column 1, paragraph 2 and Figure 1). Although Kawase does not specifically identify that their device comprises an actuator and a drive current generation unit, it is well understood that the device would include these components as Kawase does teach that the BOTAS device controls the forearm position by moving it towards the position of the estimated elbow angle at a constant velocity and controlled hand opening (page 5, column 1, paragraph 3-column 2, paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the method of administering bone marrow mononuclear cells to patients after a stroke and having them perform a weekly exercise routine of Bhasin with the BOTAS assistive movement device of Kawase to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Takeuchi teaches that muscle activity-dependent stimulation is not applicable for the stroke patients with severe hemiparesis who have no voluntary muscle activation. Therefore, these patients require activity-dependent stimulation paradigms based on brain activity. It is postulated that the re-establishment of the disrupted sensorimotor loop by integrating movement intention and passive limb movement, assisted by a robot, will strengthen the associative connection. As such, it would have been obvious to expand the method of Bhasin to include stroke patients with hand paresis by using the BOTAS device for the small hand muscle exercises as Takeuchi teaches that this activity-dependent stimulation may help with the re-establishment of the disrupted sensorimotor loop by integrating movement intention and passive limb movement and Bhasin teaches that their exercise routine caused increased BDNF levels in their patients. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 37, Bhasin teaches that the patients underwent 8 weeks of neuromotor rehabilitation and examined VEGF and BDNF levels two months after they administered the cell infusion of BM-MNCs (i.e. after the 8 weeks of rehabilitation) (page 109, paragraphs 1-2). As such, the cell infusion would had to have occurred within 4 weeks before the patients started the exercise routine
Regarding claim 38, Bhasin teaches that 5 patients between the two groups suffered a cardioembolic stroke (i.e. cardiogenic brain embolism syndrome) and one of the stroke patients that underwent the study suffered from a right lacunar infarction (table 1, CE stroke subtype and table 2, first subject of Group 2).
Response to Arguments
Applicant's arguments filed December 18, 2025, are acknowledged.
Applicant argues that the rehabilitation exercises of Bhasin are motor imagery training and mirror therapy and that imagery training is not the same as physical exercise. Applicant also argues that the general physical exercise training of Bhasin involving cycling, walking, squats and step-ups and step-downs do not fall within the physical exercise of the claimed invention. Furthermore, the physical exercises of Bhasin are for lower limbs and not the paralyzed upper limbs (page 8, paragraph 4-page 9, paragraph 2).
Applicant's arguments have been fully considered but they are not persuasive.
As an initial matter, the specification discloses that the physical exercise performed by the subject in order to restore a physical function is a physical activity that is performed in a planned and intentional way in order to improve physical strength and that can be continued (page 8, lines 19-22). The motor imagery training exercises (physical activity including small hand muscle exercises) and the general aerobic exercises of Bhasin would fall within this definition as these are planned exercises to improve motor function (which they did (page 112, paragraph 1)) and were continued for 8 weeks as part of the neurorehabilitation regime. As such, the exercises of Bhasin would fall within the Applicant’s own definition. As it relates to using assistive movement devices, as identified above, it would have been obvious to use the BOTAS device of Kawase for the small hand muscle exercises of Bhasin as Takeuchi teaches that this activity-dependent stimulation may help with the re-establishment of the disrupted sensorimotor loop by integrating movement intention and passive limb movement and Bhasin teaches that their exercise routine caused increased BDNF levels in their patients
Furthermore, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the physical exercise does not include mirror therapy and must be associated with the parlyzed limb) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claim 33 does not identify any features of the type of physical exercise, only that the physical exercise promotes bidirectional feedback between the central and peripheral nerves and is performed using an assistive movement. As such, the broadest reasonable interpretation of physical exercise is any physical exercise using an assistive movement that promotes bidirectional feedback between the central and peripheral nerves as there are no other distinguishing features that would further limit the type of physical exercise. As stated in the rejection above, regarding the limitation, “wherein the physical exercise promotes bidirectional feedback between central and peripheral nerves”, it is recognized the exercises (such as ball squeezing) used in the study would involve communication between central and peripheral nerves, promoting communication between the two. Therefore, the combined exercises of Bhasin, Kawase, and Takeuchi fall within the limitations of claim 33.
Applicant argues that Takeuchi and Kawase only describe general robot-assisted rehabilitation and a brain-machine interface technology, respectively, and does not suggest the claimed invention (page 9, paragraph 3-page 10, paragraph 3).
Applicant's arguments have been fully considered but they are not persuasive.
As best understood, Applicant is arguing that because Bhasin does not anticipate claim 33 and Takeuchi and Kawase do not teach the missing limitation of Bhasin of performing physical exercise with an assistive movement, the combination of Bhasin, Takeuchi, and Kawase do not make the claimed invention obvious. As stated supra, Applicant’s arguments against Bhasin regarding the differences between mirror therapy and physical exercise were considered unpersuasive. Applicant does not argue against the teachings of Takeuchi and Kawase regarding the additional limitations of claim 35. Therefore, Applicant’s arguments are considered unpersuasive.
Claims 33 and 35-36 are rejected under 35 U.S.C. 103 as being unpatentable over Bhasin et al. (Cerebrovasc Dis Extra 6:107–119. 2016), Takeuchi et al. (Front. Hum. Neurosci. 9: 1-15. 2015), and Kawase et al (J. Neural Eng. 14: 1-12. 2017) as applied to claims 33 and 35 above, and further in view of Perez-Rodriguez et al. (Expert Systems with Applications 41: 3922–3934. 2014).
The teachings of Bhasin, Takeuchi, and Kawase are as discussed above.
The combined teachings of Bhasin, Takeuchi, and Kawase do not teach wherein the assistive movement device performs feedback adjustment.
Perez-Rodriguez teaches that robotic devices are becoming a popular alternative to the traditional physical therapy as a mean to enhance functional recovery after stroke; they offer more intensive practice opportunities without increasing time spent on supervision by the treating therapist. An ideal behavior for these systems would consist in emulating real therapists by providing anticipated force feedback to the patients in order to encourage and modulate neural plasticity. Perez-Rodriguez developed an anticipatory assistance-as-needed control algorithm for a multijoint robotic orthosis to be used in physical acquired brain injury neurorehabilitation. This control algorithm, based on a dysfunctional-adapted biomechanical prediction subsystem, is able to avoid patient trajectory deviations by providing them with anticipatory force-feedback. The system has been validated by means of a robotic simulator. Obtained results demonstrate through simulations that the proposed assistance-as-needed control algorithm is able to provide anticipatory actuation to the patients, avoiding trajectory deviations and tending to minimize the degree of actuation. This new actuation paradigm avoids patient slacking and increases both participation and muscle activity in such a way that neural plasticity is encouraged and modulated to reinforce motor recovery (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined BOTAs device of the combined teachings of Bhasin, Takeuchi, and Kawase with the assistance-as-needed control algorithm of Perez-Rodriguez to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Perez-Rodriguez teaches that robotic devices are used to enhance functional recovery after stroke as they offer more intensive practice opportunities without increasing time spent on supervision by the treating therapist. Perez-Rodriguez developed an anticipatory assistance-as-needed control algorithm for a multijoint (such as the BOTAS device) robotic orthosis to be used in physical acquired brain injury neurorehabilitation. This control algorithm, based on a dysfunctional-adapted biomechanical prediction subsystem, is able to avoid patient trajectory deviations by providing them with anticipatory force-feedback. This new actuation paradigm avoids patient slacking and increases both participation and muscle activity in such a way that neural plasticity is encouraged and modulated to reinforce motor recovery. As such, it would have been obvious to combine the BOTAS device with the algorithm of Perez-Rodriguez to enhance functional recovery after stroke by offering more intensive practice opportunities without increasing time spent on supervision by the treating therapist. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed December 18, 2025, are acknowledged.
Applicant argues that Perez-Rodriguez only describes a control algorithm for a robotic device and does not suggest the claimed invention. As previously argued, Bhasin doesn’t teach the claimed invention and Takeuchi, Kawase, and Perez-Rodriguez do not cure the deficiency (page 10, paragraph 4-page 11, paragraph 3).
Applicant's arguments have been fully considered but they are not persuasive.
As best understood, Applicant is arguing that because Bhasin does not anticipate claim 33 and Takeuchi, Kawase, and Perez-Rodriguez do not teach the missing limitation of Bhasin of performing physical exercise with an assistive movement, the combination of Bhasin, Takeuchi, Kawase, and Perez-Rodriguez do not make the claimed invention obvious. As stated supra, Applicant’s arguments against Bhasin were considered unpersuasive. Applicant does not argue against the teachings of Rodriguez-Perez regarding the additional limitations of claim 36. Therefore, Applicant’s arguments are considered unpersuasive.
Conclusion
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/KEENAN A BATES/Examiner, Art Unit 1631