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 March 2026.
CLAIMS UNDER EXAMINATION
Claims 3, 6, 8, 13-19, 21, 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 and a 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WITHDRAWN REJECTIONS
The rejection of claim 25 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn due to claim amendment.
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 3, 6, 8, 13-19, 21, 25-29, 33-34 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Dobson et al. (previously cited; A method for organ arrest, protection and preservation and reducing tissue injury. US20160158280) in view of Feng et al. (previously cited; Current status and perspective of liver preservation solutions. Hepatobilliary cited in IDS; Pancreat Dis Int Vol. 5 (4) 2006 pages 490-494) and Rudolph et al. (previously cited; Aldosterone target organ protection by eplerenone. Molecular and Cellular Endocrinology 217 (2014) 229-238).
Dobson teaches a composition for protecting, preserving and storing organs (See Title; Abstract; [0001]). Dobson teaches formulation as a liquid or solution ([0349]). Dobson teaches the composition is diluted with a pharmaceutically acceptable carrier, including blood, saline or a physiological ionic solution ([0246]). Therefore blood is not required.
Dobson teaches an anti-inflammatory agent, a source of magnesium and a buffer as carrier (See [0370]-[0378]). The art teaches a carrier solution comprising magnesium (a cation) ([0363] [0710]) and chloride and NaHCO3 (anions) ([0363] [0710]). Dobson teaches a physiological ionic solution ([0270]). Therefore the cations and anions are interpreted to be a physiologically-relevant concentrations.
Regarding the anti-inflammatory agent: Dobson teaches valproic acid, a histone deacetylase inhibitor, as an anti-inflammatory agent ([0282]). Dobson teaches histone deacetylase inhibitors may be useful for protecting the brain and other organs of the body during delayed retrieval from the prehospital or military setting to definitive care ([0601]). VPA has cytoprotective which may confer multi-organ protection ([0601]).
It is noted the art explicitly teaches the use of VPA in a solution and teaches it confers multi-organ protection.
Dobson is silent regarding the osmolarity of the solution.
Dobson does not teach a mineralocorticoid receptor antagonist.
Feng discloses preservation solutions with a mOsm/L of 310 and 320 (see Table on page 491).
Rudolph teaches aldosterone is a mineralocorticoid linked to cardiac and renal damage (Abstract). Eplerenone is an aldosterone blocker which provides marked cardiac, cerebral and renal vascular protection (page 230, left column, first paragraph). Eplerenone reduces vascular inflammation (Abstract; see page 233 right column, second paragraph; Conclusion). Eplerenone has myocardial protective properties (page 231, left column, last paragraph; see page 232, right column, last paragraph).
Rudolph also teaches the following:
Mineralocorticoid receptors are found in the kidney, heart, vasculature and brain (page 229, right column, first paragraph). The art teaches the detrimental effects of aldosterone are mediated through MR activation in these issues (same cited section).
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 organ preservation solutions.
It would have been obvious to combine the teachings of the prior art by using eplerenone in Dobson’s composition. Dobson teaches an anti-inflammatory agent and Rudolph teaches eplerenone reduces inflammation in multiple organs. One would have used eplerenone to reduce attenuate inflammation. It would have been prima facia obvious to use VPA and eplerenone since each is taught by the prior art to be used for that very same purpose. See In re Kerkoven. Therefore, then, barring unexpected results, one would reasonably expect enhanced, additive, or synergistic activity to be observed by combining the compositions or materials. One would have expected similar results since both references are directed to compositions for protecting (hence, preserving) a tissue. 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.
Eplerenone (supra) reads on claim 21.
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.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 21 July 2026 are acknowledged.
Arguments: The Applicant argues it would not have been obvious combine the teachings of Dobson and Rudolph by administering eplerenone. The Applicant argues Rudolph is directed to in vivo systemic pharmacology in living animals, while the present claims are directed to ex vivo organ preservation. The arguments state VPA is taught in Dobson as an HDAC inhibitor with cytoprotective effects useful for protecting organs during delayed retrieval from prehospital or military settings to definitive care. Therefore, the Applicant argues the compositions taught by Dobson and Rudolph are not used for the same purpose. The Applicant argues an excised organ would not have circulating aldosterone, therefore its use would not have been obvious.
Response to Arguments: Dobson teaches a composition comprising an anti-inflammatory agent for protecting organs. Rudolph teaches aldosterone causes damage to organs. Rudolph teaches eplerenone blocks aldosterone’s receptor and inhibits its effects in organs and tissues, including inflammation. While Rudolph discloses in vivo experiments, Dobson is directed to protecting and preserving organs and vessels both in vivo and ex vivo. Dobson refers to the treated organs as having “viability” and “function” ([0817]). Therefore VPA (Dobson) and Eplerenone (Rudolph) are used for the same purpose: preservation of viable, functional organs.
The arguments directed to the absence of systemic aldosterone are not persuasive. The rejection does not rely upon systemic delivery of aldosterone to an excised organ as the reason to incorporate eplerenone. Rudolph attributes the protective effect of eplerenone to mineralocorticoid receptor (MR) mediated processes occurring in the tissues. Rudolph teaches the receptors are localized in tissues. Rudolph does not support Applicant’s arguments that aldosterone/MR activity is not present in an excised organ. Rudolph explicitly teaches eplerenone is an established cardiac (heart) and renal (kidney) protective agent, with a direct effect on cells and signaling events driving organ protection (supa; page 236, left column). The person of ordinary skill would include the antagonist taught by Rudolph to provide its organ protecting effects.
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the APIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
Prosecution Insights