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 .
Response to Arguments
Applicant’s arguments, see pages 6-9, filed 18 May 2026, with respect to the rejection(s) of claim(s) 1-16 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection has been made with respect to claims 1-16.
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 1–16 is/are rejected under 35 U.S.C. §103 as being unpatentable over O’Neill et al. (US 10,968,167, hereafter “US’167”) in view of WO 2009/052116 (hereafter “WO’116”), further in view of Rabinovitch et al. (US 9,868,953, hereafter “US’953”), and further in view of EP 4,125,359 (hereafter “EP’359”).
US’167 discloses 2,2,2-trifluoroacetic acid 1-(2,4-dimethylphenyl)-2-[(3-methoxyphenyl)methylene]hydrazide, also known as J147. US’167 further discloses that J147 is a potent orally active neurotrophic agent and provides its structure as Formula I. See US’167, col. 1, ll. 23–34. US’167 further teaches that J147 is broadly neuroprotective and exhibited activity in assays indicating neurotoxicity pathways related to aging and neurodegenerative diseases. See US’167, col. 1, ll. 46–61. The J147 compound disclosed in US’167 is the same compound recited as Formula IV in the instant claims, including the trifluoroacetyl group, hydrazone linkage, 2,4-dimethylphenyl group, and 3-methoxyphenylmethylene group.
WO’116 teaches biological activity of J147 against oxidative stress and ischemia-related cell injury. WO’116 discloses oxidative-stress assays using HT22 cells exposed to glutamate, with cell viability determined by MTT assay. See WO’116, ¶¶[0109]–[0111]. WO’116 specifically teaches that J147 exhibited an EC50 of about 5 nM following 5 mM glutamate exposure. See WO’116, ¶[0111]. WO’116 further teaches chemical-ischemia testing and states that J147 protected nerve cells from chemical ischemia induced by iodoacetic acid. See WO’116, ¶[0014], ¶¶[0124]–[0126]. WO’116 also states that exemplary compounds, including J147, have excellent neuroprotective activity. See WO’116, ¶[0143].
US’953 teaches methods for preventing ischemia-reperfusion injury in organs, including transplanted donor organs. US’953 states that the invention relates to prevention of ischemia-reperfusion injury in organs, including native organs in vivo, reimplantations, and transplantations of donor organs, and that the methods entail contacting the organ in vivo or ex vivo. See US’953, col. 1, ll. 15–27. US’953 further teaches that ischemia-reperfusion injury is cellular damage caused when blood supply returns after ischemia and that restoration of circulation results in oxidative damage, cellular dysfunction, apoptosis, and necrosis. See US’953, col. 1, ll. 30–40. US’953 also teaches that cold storage prior to transplantation followed by oxidative stress after restoration of blood supply can initiate injury, and that renal tubular cell dysfunction and apoptotic cell death are hallmarks of this process. See US’953, col. 2, ll. 1–5.
US’953 further teaches administration by conventional routes, including intravenous and intraarterial administration. See US’953, col. 12, ll. 22–35. US’953 also teaches intravenous injection in transplant/reimplantation settings, including administration following autograft/reimplantation or allograft/transplantation reperfusion. See US’953, col. 6, ll. 13–29.
EP’359 teaches delivery of therapeutic agents to ex vivo organs for transplant using organ perfusion solution. EP’359 teaches that therapeutic agents can be added to organ perfusion solution. See EP’359, ¶[0102]. EP’359 further teaches delivery of a therapeutic agent to an ex vivo organ for transplant by introducing the organ into an organ perfusion device having a reservoir comprising organ perfusion solution, wherein the organ perfusion solution comprises the therapeutic agent, and circulating the organ perfusion solution comprising the therapeutic agent through the organ. See EP’359, ¶[0119]; claim 45. EP’359 also teaches that the treated organ may include liver, heart, kidney, pancreas, bowel, or lung. See EP’359, ¶¶[0209]–[0210]; claims 46–47.
It would have been obvious to one of ordinary skill in the art before the effective filing date to administer the known Formula IV/J147 compound disclosed by US’167 to transplanted or transplanting organs in view of the cytoprotective and anti-ischemic activity taught by WO’116 and the transplant-organ ischemia-reperfusion injury methods taught by US’953. The motivation would have been to reduce oxidative damage, apoptosis, necrosis, reperfusion injury, and cell death in transplanted or transplanting organs because WO’116 teaches that J147 protects cells from oxidative stress and chemical ischemia, while US’953 teaches that transplant-organ injury is driven by oxidative damage, apoptosis, necrosis, and ischemia-reperfusion injury. It further would have been obvious to administer the Formula IV compound ex vivo or in a perfusion fluid as taught by EP’359 because EP’359 teaches using organ perfusion solution as a vehicle to deliver therapeutic agents to ex vivo organs for transplant.
Claim 1 recites administering a compound of Formula I to inhibit, reduce, delay, or prevent rejection, injury, or cell death of a transplanted organ. US’167 discloses the Formula IV/J147 compound, which falls within the Formula I genus. See US’167, col. 1, ll. 23–34. WO’116 teaches that J147 protects against oxidative stress and chemical ischemia. See WO’116, ¶¶[0109]–[0111], ¶¶[0124]–[0126]. US’953 teaches that transplant-organ ischemia-reperfusion injury involves oxidative damage, apoptosis, necrosis, and cellular dysfunction. See US’953, col. 1, ll. 30–40; col. 2, ll. 1–5. Therefore, administration of the known Formula IV/J147 compound for reducing injury or cell death of a transplanted organ would have been obvious.
Claim 2 limits the compound to Formula IV. US’167 discloses the same J147 compound recited as Formula IV. See US’167, col. 1, ll. 23–34.
Claim 3 recites an ex vivo or in vitro method of preparing an organ for transplantation by contacting the organ with Formula IV. US’953 teaches contacting an organ in vivo or ex vivo to prevent ischemia-reperfusion injury in transplant/reimplantation contexts. See US’953, col. 1, ll. 15–27. EP’359 teaches delivery of a therapeutic agent to an ex vivo organ for transplant by circulating an organ perfusion solution comprising the therapeutic agent through the organ. See EP’359, ¶[0119]; claim 45. US’167 supplies the Formula IV/J147 compound, and WO’116 supplies its cytoprotective/anti-ischemic activity.
Claim 4 recites an in situ or in vivo method of preparing an organ for transplantation by contacting the organ prior to removal from a donor subject. US’953 teaches prevention of ischemia-reperfusion injury in native organs in vivo, reimplantations, and transplantations of donor organs, and teaches contacting organs in vivo or ex vivo. See US’953, col. 1, ll. 15–27. The use of the known J147 compound for in vivo donor-organ treatment would have been obvious in view of WO’116’s teaching that J147 protects cells from oxidative stress and chemical ischemia. See WO’116, ¶¶[0109]–[0111], ¶¶[0124]–[0126].
Claims 5 and 6 recite inhibition, reduction, delay, or prevention of reperfusion injury and cell death in the transplanted organ. US’953 teaches transplant-organ ischemia-reperfusion injury and identifies oxidative damage, apoptosis, necrosis, and cellular dysfunction as mechanisms of such injury. See US’953, col. 1, ll. 30–40; col. 2, ll. 1–5. WO’116 teaches that J147 protects cells from oxidative stress and chemical ischemia. See WO’116, ¶¶[0109]–[0111], ¶¶[0124]–[0126]. The claimed results would have been reasonably expected from the combined teachings.
Claims 7 and 8 recite reduction of cell death in ex vivo/in vitro and in situ organ-preparation methods. US’953 teaches in vivo and ex vivo contacting of organs to prevent ischemia-reperfusion injury in transplant contexts. See US’953, col. 1, ll. 15–27. WO’116 teaches the cytoprotective effect of J147 against oxidative stress and chemical ischemia. See WO’116, ¶¶[0109]–[0111], ¶¶[0124]–[0126].
Claims 9–11 recite administering Formula IV to the organ before transplantation, before removal from the donor, or after removal and before transplantation. US’953 teaches transplant-organ treatment in vivo and ex vivo to prevent ischemia-reperfusion injury. See US’953, col. 1, ll. 15–27. EP’359 teaches delivery of a therapeutic agent to an ex vivo organ for transplant by circulating organ perfusion solution comprising the therapeutic agent through the organ. See EP’359, ¶[0119]; claim 45. These references render obvious administration before removal, after removal, and before transplantation as routine timing options in transplant-organ treatment and preservation.
Claims 12 and 13 recite intravenous, intra-arterial, and oral administration to the subject. US’167 teaches that J147 is orally active. See US’167, col. 1, ll. 28–34. US’953 teaches administration by conventional routes including oral, intravenous, and intraarterial administration. See US’953, col. 12, ll. 22–35. US’953 further teaches intravenous injection in transplant/reimplantation settings. See US’953, col. 6, ll. 13–29. Selection of intravenous, intra-arterial, or oral administration would have been a routine choice for delivering a known therapeutic compound.
Claim 14 recites local administration or administration in a perfusion fluid in the ex vivo organ preparation method. EP’359 teaches that therapeutic agents can be added to organ perfusion solution. See EP’359, ¶[0102]. EP’359 further teaches circulating an organ perfusion solution comprising a therapeutic agent through an ex vivo organ for transplant. See EP’359, ¶[0119]; claim 45. Thus, administering the Formula IV compound in a perfusion fluid would have been obvious.
Claim 15 recites local or perfusion-fluid administration during the step of administering Formula IV to the organ prior to transplantation. EP’359 teaches the same perfusion-fluid delivery of a therapeutic agent to an ex vivo transplant organ. See EP’359, ¶[0119]; claim 45. US’167 supplies the Formula IV/J147 compound, and WO’116 supplies its cytoprotective and anti-ischemic rationale.
Claim 16 recites administration to the donor subject intravenously or intra-arterially. US’953 teaches in vivo organ treatment in transplant contexts. See US’953, col. 1, ll. 15–27. US’953 also teaches intravenous and intraarterial administration. See US’953, col. 12, ll. 22–35; col. 6, ll. 13–29. It would have been obvious to administer the known cytoprotective J147 compound by intravenous or intra-arterial route to a donor subject to deliver the compound to the organ before removal.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEBORAH D CARR whose telephone number is (571)272-0637. The examiner can normally be reached Monday-Friday (10:30 am -6:30 pm).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at 572-272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DEBORAH D CARR/Primary Examiner, Art Unit 1691
Prosecution Insights