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 23 July 2025.
CLAIMS UNDER EXAMINATION
Claims 3, 6, 8, 13-19, 21, 23, 25-29, 33-34 and 55 are pending and have been examined on their merits.
PRIORITY
The earliest priority document filed by the Applicant is Provisional Application 62/892,917, filed on 28 August 2019. It does not provide support for a preservation fluid comprising a mineralocorticoid receptor antagonist, aldehyde dehydrogenase agonist, and/or histone deacetylase inhibitor. Provisional Application 62/976,719, filed on 14 February 2020, provides support for the limitations recited in Claim 26.
WITHDRAWN REJECTIONS
The rejection of claims 6, 25 and 34 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn due to claim amendment.
The rejections made under 35 U.S.C. 103 have been withdrawn due to claim amendment.
REJECTIONS
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 25 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 25 has been amended to recite “nicotinic acid derivatives”. The specification recites “NA derivatives”, but does not provide support for “nicotinic acid derivatives”.
An amendment to the claims or the addition of a new claim must be supported by the description of the invention in the application as filed. In re Wright, 866 F.2d 422, 9 USPQ2d 1649 (Fed. Cir. 1989). Applicant is required to cancel the new matter in the reply to this Office Action.
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 3, 6, 8, 13-19, 25-29, 33-34 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Dobson et al. (A method for organ arrest, protection and preservation and reducing tissue injury. US20160158280) in view of Feng et al. (Current status and perspective of liver preservation solutions. Hepatobilliary cited in IDS; Pancreat Dis Int Vol. 5 (4) 2006 pages 490-494).
Dobson teaches a composition for storing organs (Abstract; [0001]). A preferred composition includes (i) at least one of a potassium channel opener, a potassium channel agonist and an adenosine receptor agonist; (ii) an antiarrhythmic agent or a local anesthetic; (iii) a citrate and one or more of an anti-inflammatory agent, antioxidant, a source of magnesium and a pharmaceutically acceptable carrier such as a buffer. See [0370]-[0378].
The art teaches buffering compounds (hence, a buffer) ([0365]).
The art teaches a carrier solution comprising magnesium (a cation) ([0363] [0710])
and chloride and NaHCO3 (anions) ([0363] [0710]).
The composition comprises an anti-inflammatory agent. Valproic acid as an anti-inflammatory agent ([0282]). Valproic acid (VPA) is a histone deacetylase inhibitor that may decrease cellular metabolic needs following traumatic injury. Valproic acid (VPA) has proven to be beneficial after traumatic injury and has been shown to improve survival in lethal models of hemorrhagic shock ([0282]). It is noted the art explicitly teaches the use of VPA in a solution and teaches it confers multi-organ protection. Therefore the art teaches a histone deacetylase inhibitor.
The art teaches formulation as a liquid or solution ([0349]). The composition contains water ([0349]).
Dobson teaches a physiological ionic solution ([0270]). Therefore the cations and anions are interpreted to be a physiologically-relevant concentrations.
Dobson is silent regarding the osmolarity of the solution.
Feng discloses preservation solutions with a mOsm/L of 310 and 320 (see Table on page 491).
It would have been obvious to prepare a preservation solution with an osmolarity of 310-320 mOsm/L. Dobson teaches a preservation solution and Feng discloses preservation solutions have an osmolarity of 310-320 mOsm/L One would have been motivated to do so to preserve an organ in a physiological solution. One would have had a reasonable expectation of success since Feng teaches solutions with the claimed osmolarity can preserve an organ. One would have expected similar results since both references are directed to rogan preservation solutions. Therefore claim 26 is rendered obvious.
Dobson teaches a histone deacetylase inhibitor that is an anti-inflammatory agent (VPA; supra). The concentration of anti-inflammatory agent in the composition may be preferably 0.001 mM to 50 mM and most preferably 0.1 mM to 10 mM ([0289]). Therefore claim 3 is rendered obvious.
Dobson teaches magnesium and chloride ([0363]). Therefore claim 6 is rejected.
Dobson teaches dextran as a colloid ([0319). Therefore claim 8 is included in this rejection.
Dobson teaches the use of buffer solutions that contain NaCl (sodium and chloride), glucose, NaH2PO4 (phosphate buffer) and NaHCO3 (bicarbonate buffer) ([0363]). An osmolarity of 310-320 mOsm/L is rendered obvious on the ground set forth above. Therefore claim 13 is rejected.
Dobson teaches the use of buffer solutions that contain NaCl (sodium and chloride), magnesium, a phosphate buffer, KCl (potassium) ([0363]). The composition can contain lactobionate ([0415]), raffinose ([0318]), hydroxyethyl starch ([0318]), allopurinol ([0343]) and glutathione ([0343]). An osmolarity of 310-320 mOsm/L is rendered obvious on the ground set forth above. Therefore claim 14 is rejected.
Dobson teaches a composition comprising NaCl (sodium and chloride), KCl (potassium), CaCl2 (calcium), MgCl2 (magnesium), histidine, tryptophan, mannitol and alpha-ketoglutarate ([0728]). An osmolarity of 310-320 mOsm/L is rendered obvious on the ground set forth above. Therefore claim 15 is included in this rejection.
Dobson teaches a composition (HTK solution) comprising NaCl (sodium), KCl (potassium), histidine and mannitol ([0728]). Dobson teaches addition of lactobionate to HTK ([0842]). The art teaches glutathione can be used as an antioxidant ([0343]). An osmolarity of 310-320 mOsm/L is rendered obvious on the ground set forth above. Therefore claim 16 is included in this rejection.
The art teaches sodium, potassium, calcium, magnesium, chloride, phosphate buffer, dextran (supra) and sulfate (MgSO4). An osmolarity of 310-320 mOsm/L is rendered obvious on the ground set forth above. Therefore claim 17 is rejected.
Dobson teaches a heparinised buffer ([0733]). The buffer contains heparin, NaCl (sodium), KCl (potassium) ([0734]. Dobson teaches the use of mannitol to minimize cellular water uptake ([0318]), albumin as a colloid ([0320]) and blood as a carrier ([0327]). The skilled artisan would optimize the ionic concentration to obtain the desired osmolarity. Therefore claim 18 is included in this rejection.
Th art teaches sodium, potassium, calcium, magnesium, chloride and bicarbonate (supra). An osmolarity of 310-320 mOsm/L is rendered obvious on the ground set forth above. Therefore claim 19 is rejected.
Dobson teaches valproic acid (supra). Therefore claim 25 is included in this rejection.
Dobson teaches perfusion of an organ ([0187] [0390] [0395]). Therefore claim 27 is included in this rejection.
Dobson teaches the composition is highly beneficial at about 10° C or at arrange of about 0° C. to about 5° C ([0411]). Therefore claim 28 is rendered obvious.
Dobson teaches the organ can be heart, lung, liver and pancreas ([0218]).Therefore claim 29 is rejected.
Dobson teaches the organ can be a heart ([0218]). Therefore claim 33 is rejected.
Dobson teaches a cardioplegic solution is a solution that temporarily and reversibly stops or arrests the heart from beating ([0147]). It contains high potassium as the arresting agent for the heart and other organs ([0149]). The solution is used as a method for arrest and protection to undertake an operation ([0149]). Therefore claim 34 is rendered obvious.
Dobson teaches valproic acid (supra). Therefore claim 55 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Dobson in view of Feng as applied to claim 26 above, and further in view of Delgado et al. (cited in IDS; Compositions And Methods For Preserving Red Blood Cells. WO2008/089337).
Claim 26 is rejected on the grounds set forth above. The teachings of Dobson and Feng are reiterated.
Dobson teaches a preservation solution. The art teaches the composition may be administered with blood or a blood product ([0401]).
Dobson does not teach the use of a mineralocorticoid antagonists recited in claim 21.
Delgado teaches a composition and method for preserving red blood cells and preventing red blood cell storage lesions (Abstract). The composition comprises at least one potassium sparing agent. The potassium agent is selected from spironolactone, eplerone, amiloride and triamterene (page 2, lines 4-10; claim 15 of Delgado). The art teaches potassium sparing drugs prevent storage related potassium leakage (see first paragraph of page 7).
It would have been obvious to include eplerone in the solution taught by Dobson. One would have been motivated to do so since Dobson teaches a composition comprising blood (which inherently contains red blood cells) and Delgado teaches adding potassium sparing agent, including eplerone, to a solution comprising red blood cells. One would do so to stabilize red blood cells, as taught by Delgado. KSR Rationale E indicates that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and commonsense” (MPEP 2143 “Rationale E. Obvious to Try” section). One would have had a reasonable expectation of success since Delgado teaches eplerone can be used with red blood cells. One would have expected similar results since both references are directed to compositions for preserving a tissue. Claim 21 is rendered obvious.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Dobson in view of Feng as applied to claim 26 above, and further in view of Zhang et al. (previously cited; Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress, Free Radical Research, 2018 52:6, 629-638).
Claim 26 is rejected on the grounds stated above. The teachings of the prior art are reiterated.
Dobson does not teach the use of Alda-1
Zhang teaches liver ischemia/reperfusion (I/R) injury is a life-threatening condition resulting from liver transplantation, hepatectomy, shock, or trauma (first paragraph of Introduction on page 629). Oxidative stress is one of the key factors in the pathogenesis of hepatic I/R injury (second paragraph of Introduction on page 629).
Zhang we investigated the effects of the ALDH2 activator Alda-1 on hepatic I/R injury. Partial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of reperfusion. Rats received either Alda-1 or vehicle by intravenous injection 30 min before ischemia (Abstract). Pretreatment with Alda-1 significantly alleviated I/R-induced elevations of alanine aminotransferase and aspartate amino transferase, and significantly blunted the pathological injury of the liver (see Abstract; see Results section on page 633 above Figure 2) . Moreover, Alda-1 significantly inhibited ROS and proinflammatory cytokines production, 4-HNE and MDA accumulation, and apoptosis (Abstract).
It would have been obvious to combine the teachings of the prior art by using Alda-1 in the composition taught by Dobson. One would have been motivated to do so since Dobson teaches a composition for protecting an organ from ischemic damage, and Zhang teaches Alda-1 can protect an organ from ischemic injury. The skilled artisan one would combine agents known to protect against ischemia to achieve an enhanced affect. In re Kerkoven (205 USPQ 1069) in which it was shown to be prima facia obvious to combine compositions, each of which is taught by the prior art to be used for that very same purpose. One would have had a reasonable expectation of agent protects organs from ischemic injury. One would have expected similar results since each reference is directed to organ preservation. Therefore claim 23 is rendered obvious.
Therefore Applicants Invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 23 July 2025. The Applicant argues the rejections rely on Delgado, which teaches spironolactone. The amended claims exclude spironolactone. The Applicant argues the previous rejections do not meet the claim limitations.
EXAMINER’S RESPONSE
The arguments are not persuasive. New grounds of rejection have been set forth above. Dobson does not require spironolactone or hydroxamic acid, which are not excluded in claim 26. Examiner notes Delgado does require spironolactone. The art teaches eplerone (an alternative mineralocorticoid receptor antagonist).
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 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