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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 30 December 2025.
CLAIMS UNDER EXAMINATION
Claims 10-14, 17, 19-20 are pending and have been examined on their merits.
PRIORITY
Provisional Application 62/162,739 filed on 16 May 2015 is acknowledged.
REJECTIONS
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 10-12, 17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Keirstead et al. (previously cited; Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord Injury. The Journal of Neuroscience, 2005; 25(19):4694–4705) in view of Keirstead et al. (previously cited; Oligodendrocytes derived from human embryonic stem cells for remyelination and treatment of spinal cord injury. Patent US7285415. 2007) as evidenced by Nistor et al. (Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia. 2005 Feb;49(3):385-96) and Priest et al. (Preclinical Safety of Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Supporting Clinical Trials in Spinal Cord Injury, Regenerative Medicine, 2015 10:8, 939-958).
Keirstead (2005) determines the efficacy of using human stem cell derivatives to promote remyelination and functional recovery in the injured adult rat spinal cord (Abstract). Keirstead teaches a spinal cord injury caused by a contusion injury induced by a compactor (see page 4695, left column; “Experimental groups”; see right column “Spinal cord injury”). This is interpreted to be an acute spinal cord injury.
Keirstead teaches human embryonic stem cells (hESCs) were induced to differentiate into high purity oligodendrocyte progenitor cells (OPCs). High-purity OPCs were then transplanted into spinal cord injury (SCI) sites (see 4694, right column, second paragraph). Cells are injected (see Abstract). Keirstead administers 1.5 million OPCs following spinal cord injury (see page 4695, left column, “Experimental groups”; see right column “Spinal cord injury”). This is interpreted to be an effective amount.
Regarding the OPCs:
Keirstead teaches hESC are differentiated using the protocol taught by Nistor et al., 2005 (see “Cell culture”; first paragraph of Materials and Methods; see page 4703, right column, first paragraph). Keirstead teaches Nistor 2005 is “Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396”.
As evidenced by Preist et al., the cells made using the protocol taught in Nistor et al. are known as “AST-OPC1” cells (see page 939, left column, second paragraph; Nistor is cited as reference 7 in “References section”). As evidenced by Preist et al., these cells were first developed by the Generon Corporation and acquired by Asterias (page 939, last paragraph of left column bridging first paragraph to right column). As evidenced by Priest et al., “AST-OCP1” cells produce MCP-1, TIMP1, TMP2 and ApoE (see page 943, right column, first paragraph of “Biological activities of AST-OPC-1). Because Keirstead teaches the same method as Nistor 2005, it would produce the same cells. The cells would inherently secrete the same factors. See MPEP 2112.02.
Because Keirstead teaches the claimed composition of OPCs, it is adapted for cryopreservation.
Keirstead teaches human pluripotent stem cell derived oligodendrocyte progenitor cells.
Keirstead injects the cells into the spinal cord of a subject.
As evidenced by Priest, the cells disclosed by Keirstead are inherently capable of producing MCP-1, TIMP1, TIMP2 and ApoE.
The deficiencies of Keirstead are:
Keirstead does not treat a human.
Keirstead (2007) discloses oligodendrocytes derived from human embryonic stem cells for remyelination and treatment of spinal cord injury (Title). A human embryonic stem cell is a human pluripotent stem cell. Therefore the cells taught by Keirstead read on human pluripotent stem cell-derived OPCs. While Keirstead restores spinal cord function in a rat (Example 2), Keirstead teaches the cells can be used to treat humans or non-humans (column 3, lines 35-39) for human or animal therapy (column 4, lines 13-14). Keirstead teaches the cells can be administered by way of a needle (hence, injected; column 21, lines 33-35).
Keirstead (2007) also teaches the following regarding OPCs:
Keirstead produces OPCs by differentiating H1 human embryonic stem cells (Example 1). Cells are cultured in feeder free and serum free conditions. The medium contains bFGF (column 22; see Example 1, line 40-42). Cells are then cultured in 50% glial precursor medium (GPM) and 4 ng/ml bFGF (see column 23, lines 20-21; Table 1). The art teaches culturing in 20 ng/ml EGF (see column 23 lines 45-55). The art teaches “full strength” GPM is used for culture after day 2 (Table 1). On day 28, cells are plated on Matrigel and cultured in media containing GPM and EGF (see Table 1). Cells are fixed with formaldehyde on day 42 (column 24, lines 22-24). Therefore cells are cultured for 41 days.
The specification discloses AST-OPC cells secrete MCP1, clusterin, APOE, TIMP1 and TIMP 2 ([0181]) Table 1. To produce said cells, H1 human embryonic stem cells are cultured using feeder free and serum free conditions ([0151]). The specification discloses the cells are cultured in 50% glial progenitor medium containing 4 ng/ml bFGF ([0151]). The art teaches culturing in 20 ng/ml EGF ([0151]). At day 2, “full strength” GPM is used for culture ([0151]). On day 28, cells are plated on Matrigel and cultured in GPM and EGF. Cells are cultured for 41 days ([0151])
Because Keirstead cultures the same H1 human embryonic stem cell line using the same method to produce OPCs, the cells would inherently be capable of secreting MCP-1, APOE, TIMP1 and TIMP 2 and forming a tissue matrix in a spinal cord injury site of a human within about 180 days or less after being injected.
It would have been obvious to treat a human using the OPCs taught by Keirstead (2005). One would have been motivated to do so since Keirstead (2005) teaches human OPCs can induce remyelination in the spinal cord and Keirstead (2007) teaches human OPCs can be administered to remyelinate the spinal cord. One would administer human OPCs to treat an acute spinal cord injury in a human. One would have had a reasonable expectation of success since Keirstead (2007) teaches humans can be treated using human OPCs. One would have expected similar results since both references use OPCs derived from human embryonic stem cells to repair myelin in a spinal cord injury. Because the cells taught by Keirstead (2005) are capable of secreting the claimed factors, they would be capable of forming a tissue matrix at a spinal cord injury as recited in claim 10. Therefore claim 10 is rendered obvious.
Keirstead (2005) teaches cell suspensions were injected along the midline of the spinal cord at a depth of 1.2 mm into one site 4mm cranial to the lesion epicenter and one site 4mm caudal to the lesion epicenter ,in a total volume of either 2.5 µl (250,000 cells) or 15 µl (1,500,000 cells) (see page 4695, see right column “Cell transplantation”). Therefore claim 11 is included in this rejection.
Because Keirstead injects OPCs that are capable of secreting MCP-1, APOE, TIMP1 and TIMP 2, they would be expected to have the characteristics recited in claim 12 following administration.
Keirstead (2005) teaches OPC administration results in remyelination. Therefore the spinal cord injury taught by the reference is interpreted to be a traumatic injury results in a loss of myelination. Claim 17 is included in this rejection.
Keirstead (2005) does not teach a subject with cervical injury.
Keirstead (2007) treats a subject with spinal cord injury (SCI). Keirstead (2007) teaches a spinal cord injury can occur at various locations, including injuries to the cervical and thoracic spine (column 21, lines 25-30).
It would have been obvious to treat a cervical spinal cord injury. One would have been motivated to do so since Keirstead induces remyelination in a subject with spinal cord injury and the art teaches the injuries can be thoracic or cervical. The skilled artisan would administer a treatment known to induce remyelination to treat an SCI at either region. One would have expected similar results since Keirstead teaches these injuries can be treated. Therefore claim 19 is rendered obvious.
Keirstead (2005) teaches the contusion injury is at the thoracic level (see page 4695, left column, paragraph titled “Experimental groups”). Therefore claim 20 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 30 December 2015 are acknowledged.
Argument 1: The Applicant notes the claim 10 has been amended to exclude the previously recited dose. The Applicant states the amended claim now has priority to the 62/162739 filing fate of 16 May 2015. The Applicant argues Priest is no longer prior art in light of the claim amendment.
Response to Argument 1: Priest is not used as prior art. It is cited as a post-filing evidentiary reference. Keirstead (prior art; 2005) teaches hESC are differentiated using the same protocol taught by Nistor et al., 2005 (see “Cell culture”; first paragraph of Materials and Methods; see page 4703, right column, first paragraph). Keirstead teaches Nistor (2005; available as prior art) is “Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396”.
As evidenced by Preist et al. (post-filing evidentiary reference), the cells made using the protocol taught in Nistor et al. are known as “AST-OPC1” cells (see page 939, left column, second paragraph; Nistor is cited as reference 7 in “References section”). As evidenced by Preist et al., these cells were first developed by the Generon Corporation and acquired by Asterias (page 939, last paragraph of left column bridging first paragraph to right column). As evidenced by Priest et al., “AST-OCP1” cells produce MCP-1, TIMP1, TMP2 and ApoE (see page 943, right column, first paragraph of “Biological activities of AST-OPC-1).
Secretion of MCP-1, TIMP1, TMP2 and ApoE is an inherent property of the cells taught in Nistor (available as prior art). Because Keirstead uses the same method taught in Nistor, the cells would inherently secrete MCP-1, TIMP1, TMP2 and ApoE. See MPEP 2112.02. Therefore the argument is not persuasive.
Argument 2: The Applicant argues the prior art does not teach the claimed composition is “adapted for cryopreservation”.
Response to Argument 2: Examiner notes the claim does not require cryopreservation; the claims are injected into the human spine. The composition does not require a cryopreservative. The composition contains oligodendrocyte progenitor cells (OPCs). Keirstead teaches a composition containing OPCs. Therefore it is adapted for cryopreservation.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Keirstead (2005) in view of Keirstead (2007) as recited in the rejection of claim 10 above, and further in view of Goldman et al. (previously cited; Treating myelin diseases with optimized cell preparations. US 2011/0059055 A1) as evidenced by Vigil et al. (previously cited; Efficacy of tacrolimus in inhibiting inflammation caused by carrageenan in a murine model of air pouch. Transplant Immunology Volume 19, Issue 1, April 2008, Pages 25-29).
Claim 10 is rejected on the grounds rejected above. The teachings of the Keirstead references are reiterated.
The Keirstead references administer OPCs to a subject.
The Keirstead references are silent regarding treatment to reduce immune rejection of the OPCs (claim 13).
Goldman is directed to oligodendrocyte-biased glial progenitor cells and methods of making, isolating, and using such cells (Abstract). Delivery of the cells to the subject can include either a single step or a multiple step injection directly into the nervous system ([0055]).
Goldman teaches the following at [0053]:
Since the CNS is a immunologically privileged site, transplanted cells, including xenogeneic, can survive and, optionally, no immunosuppressant drugs or a typical regimen of immunosuppressant agents are used in the treatment methods. The methods of treatment, however, optionally further comprise administering an immunosuppressant agent to the subject Immunosuppressant agents and their dosing regimens are known to one of skill in the art and include such agents as Azathioprine, Azathioprine Sodium, Cyclosporine, Daltroban, Gusperimus Trihydrochloride, Sirolimus, and Tacrolimus. Dosages ranges and duration of the regimen can be varied with the disorder being treated; the extent of rejection; the activity of the specific immunosuppressant employed; the age, body weight, general health, sex and diet of the subject; the time of administration; the route of administration; the rate of excretion of the specific immunosuppressant employed; the duration and frequency of the treatment; and drugs used in combination. One of skill in the art can determine acceptable dosages for and duration of immunosuppression. The dosage regimen can be adjusted by the individual physician in the event of any contraindications or change in the subject's status.
It would have been obvious to provide an immunosuppressant to treat a spinal cord injury. One would have been motivated to do so since Keirstead (2005) administers OPCs to treat a spinal cord injury and Goldman teaches administering immunosuppressants to a subject receiving OPCs for injury to the central nervous system. One of skill would have expected success since Goldman teaches immunosuppressants can be administered for this purpose. One would have expected similar results since both references are directed to methods of transplanting OPCs to treat CNS injuries. Therefore claim 13 is rendered obvious.
As set forth above, Goldman teaches Tacrolimus. As evidenced by Vigil et al., Tacrolimus is an immunosuppressant drug (see Background section of Abstract) that has anti-inflammatory properties (see Conclusion section of Abstract). Therefore administration of an anti-inflammatory agent would have been obvious. Claim 14 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 10-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of US Patent 10286009 14 May 2019) in view of the Keirstead (2007 US7285415). Although the conflicting claims are not identical, they are not patentably distinct from each other because the method steps of the Instant Application encompass claim limitations of the patent.
Claims 1 and 9-10 of the ‘009 Patent encompass administration of OPC cells derived from human pluripotent stem cells to a human at a site of spinal cord injury. Claim 8 reads on the dose now recited in instant claim 10. Keirstead ‘415 teaches any acute abnormalities caused by trauma to the CNS may be considered for treatment (column 21, lines 20-21). It would have been obvious to treat an acute spinal cord injury using the cells taught by Keirstead ‘009. One would have been motivated to do so since Keirstead ‘415 teaches acute trauma to the CNS (spinal cord) can be treated with OPCs. One would have had a reasonable expectation of success since Keirstead ‘415 teaches OPCs can successfully treat acute injuries.
As evidenced by the ‘009 Patent, these cells are 1) capable of secreting the factors recited in instant claim 1 (see Figure 10) and 2) are capable of forming tissue as recited in instant claim 1 (column 4, lines 42-47). These are inherent properties of the cells. The ‘009 Patents teaches OPCs that read on the claimed composition. Therefore it is adapted for cryopreservation. Claim 6 of the ‘009 Patent recites the OPCs are capable for forming a tissue matrix within about 180 days or less. Regarding claim 12: Claim 4 of the ’009 Patent states the OPCs are capable of remaining within the spinal cord injury site of said subject for a period of about 2 years or longer following the injection of the composition to the spinal cord injury site. Claim 7 of the ‘009 Patent recites the subject has a thoracic or cervical spinal cord injury. These are traumatic injuries that encompass claims 17-20 of the instant claims.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 30 December 2015 are acknowledged.
Argument 1: The Applicant argues the prior art does not teach the claimed composition is “adapted for cryopreservation”.
Response to Argument 1: Examiner notes the claim does not require cryopreservation; the claims are injected into the human spine. The composition does not require a cryopreservative. The composition contains oligodendrocyte progenitor cells (OPCs). Keirstead teaches a composition containing OPCs. Therefore it is adapted for cryopreservation.
CONCLUSION
No Claims Are Allowed
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653