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 .
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 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.
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Sept. 17, 2025 has been entered. All arguments and the Declaration under 37 CFR §1.132 submitted by M. Alexandre Lopez, Ph.D. have been fully considered.
Status of the Claims
Claims 1, 3, 6-7 and 10-23 are currently pending.
Claims 2, 4, 5, 8 and 9 are cancelled.
Claims 1, 3, 6-7 and 10-23 have been considered on the merits.
Claim Rejections - 35 USC § 112
The claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ), are withdrawn due to amendment.
Claim Rejections - 35 USC § 102
The claim rejections under 35 USC § 102 are revised upon further consideration.
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 1, 3, 10-12, and 15-18 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Lopez et al. (US 2002/0068265 A1) (ref. of record).
With respect to claim 1, Lopez teaches a method of preserving and rinsing organs in an aqueous solution (0001-0002 and 0028). Lopez teaches the aqueous solution containing sodium ions at a concentration of 30-250 mmol, specifically at 125 mmol (0017-0019 and Table 2). Lopez teaches the aqueous solution containing potassium ions at a concentration of 10-40 mmol, specifically at 25 mmol (0024-0026 and Table 2). Lopez teaches the aqueous solution containing polyethylene glycol with a molecular weight of 35,000 g/mol (PEG35000) at a concentration of 0.01 to 5 mmol (0.35-175 g/L), specifically at 25 mmol (1.02 g/L) (0020-0021 and Table 2). Lopez teaches the organ or tissue are washed of residual blood (rinsed) and that typically organs are rinsed after being removed (0002-0003 and 0007). With respect to claim 1, Lopez teaches the method where the organ is perfused with the solution (preserving is dynamic) and teaches perfusing livers with the inventive solution of Table 2 (solution of Group C) (0035-0038 and 0055).
With respect to claim 3, Lopez teaches the method where the aqueous solution is maintained at a temperature between 2 to 10°C, and specifically at a temperature of 4°C (0029). With respect to claims 10 and 11, Lopez teaches the method where the organ intended to be transplanted or preserved is liver, kidney and heart (0074 and Example II). With respect to claim 12, Lopez teaches the method where the aqueous solution contains glutathione at a concentration of 1-6 mmol, specifically at 3 mmol (0026 and Table 2). With respect to claim 15, Lopez the method where the aqueous solution has a pH between 6.5 and 8, specifically a pH of 7.4 (0024-0025 and 0032). With respect to claim 16, Lopez teaches the method where the solution further comprises an impermeant anion, a sugar, a membrane-stabilizing agent, a buffer solution, an anti-free radical agent and an energy source (0022).
With respect to claim 17, Lopez teaches the method where the aqueous solution contains raffinose at a concentration of 20-40 mmol, specifically at 30 mmol (0026 and Table 2). Lopez teaches allopurinol at a concentration of 0.5-5 mmol, specifically at 1 mmol (0026 and Table 2).
With respect to claim 18, Lopez teaches the method where the aqueous solution contains lactobionic acid at a concentration of 70-140 mmol, specifically at 100 mmol (0026 and Table 2). Lopez teaches the solution with MgSO4 (sulphate ions) at a concentration of 1-10 mmol, specifically at 5 mmol (0026 and Table 2). Lopez the solution with teaches H2PO4 (phosphate ions) at a concentration of 10-40 mmol, specifically at 25 mmol (0026 and Table 2). Lopez teaches the solution with adenosine at a concentration of 1-10 mmol specifically at 5 mmol (0026 and Table 2).
Therefore, the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
New claim rejections under 35 USC § 103 have been added to address the claim amendments upon further consideration.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 10-12, and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez et al. (US 2002/0068265 A1) (ref. of record) in view of Jochmans et al. (American Journal of Transplantation, 2016).
With respect to claim 1, Lopez teaches a method of preserving and rinsing organs in an aqueous solution (0001-0002 and 0028). Lopez teaches the aqueous solution containing sodium ions at a concentration of 30-250 mmol, specifically at 125 mmol (0017-0019 and Table 2). Lopez teaches the aqueous solution containing potassium ions at a concentration of 10-40 mmol, specifically at 25 mmol (0024-0026 and Table 2). Lopez teaches the aqueous solution containing polyethylene glycol with a molecular weight of 35,000 g/mol (PEG35000) at a concentration of 0.01 to 5 mmol (0.35-175 g/L), specifically at 25 mmol (1.02 g/L) (0020-0021 and Table 2). Lopez teaches the organ or tissue are washed of residual blood (rinsed) and that typically organs are rinsed after being removed (0002-0003 and 0007).
With respect to claim 1, Lopez teaches the method where the organ is perfused with the solution (preserving is dynamic) and teaches perfusing livers with the inventive solution of Table 2 (solution of Group C) (0035-0038 and 0055). It appears from these teachings that claim 1 is anticipated by Lopez as explained in the rejections under 35 U.S.C. § 102, however, if the limitation of dynamic preservation is shown not to be taught by Lopez, it would have been obvious to one of ordinary skill in the art to modify the method of Lopez to use the aqueous solution for dynamic preservation.
In support, Jochmans teaches in the beginning of transplantation technology that dynamic preservation was the only way to preserve deceased organs and currently dynamic preservation strategies are being used to optimize organ preservation, to allow for real-time graft viability assessment, and as mode for delivering condition agents to repair damaged organs (abstract and pg. 2546 Col. 1 para. 1). Jochmans teaches dynamic preservation strategies allow for improved organ quality and utilization (pg. 2546 Col. 1 para. 1). In further support, Lopez teaches the desire for one solution for preserving organs (0006-0015).
Accordingly at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Lopez so that the exposing of the organ includes dynamic preservation for the benefit of improving the organ quality as taught by Jochmans. It would have been obvious to one of ordinary skill in the art to modify the method of Lopez so that the exposing of the organ includes dynamic preservation, since dynamic preservation was well-known in the art at the time and was known for the benefits of optimizing organ preservation, allowing for real-time graft viability assessment, and as a mode for delivering condition agents to repair damaged organs as taught by Jochmans. It would have been obvious to one of ordinary skill in art to use the preservation solution taught by Lopez in dynamic preservation, since Lopez teaches the desire for one solution and Jochmans teaches the benefits of dynamic preservation. One of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Lopez, since dynamic preservation was known in the art in methods of exposing organs intended for transplantation to an aqueous solution to preserve the organ as taught by Jochmans.
With respect to claim 3, Lopez teaches the method where the aqueous solution is maintained at a temperature between 2 to 10°C, and specifically at a temperature of 4°C (0029). With respect to claims 10 and 11, Lopez teaches the method where the organ intended to be transplanted or preserved is liver, kidney and heart (0074 and Example II). With respect to claim 12, Lopez teaches the method where the aqueous solution contains glutathione at a concentration of 1-6 mmol, specifically at 3 mmol (0026 and Table 2). With respect to claim 15, Lopez the method where the aqueous solution has a pH between 6.5 and 8, specifically a pH of 7.4 (0024-0025 and 0032). With respect to claim 16, Lopez teaches the method where the solution further comprises an impermeant anion, a sugar, a membrane-stabilizing agent, a buffer solution, an anti-free radical agent and an energy source (0022).
With respect to claim 17, Lopez teaches the method where the aqueous solution contains raffinose at a concentration of 20-40 mmol, specifically at 30 mmol (0026 and Table 2). Lopez teaches allopurinol at a concentration of 0.5-5 mmol, specifically at 1 mmol (0026 and Table 2).
With respect to claim 18, Lopez teaches the method where the aqueous solution contains lactobionic acid at a concentration of 70-140 mmol, specifically at 100 mmol (0026 and Table 2). Lopez teaches the solution with MgSO4 (sulphate ions) at a concentration of 1-10 mmol, specifically at 5 mmol (0026 and Table 2). Lopez the solution with teaches H2PO4 (phosphate ions) at a concentration of 10-40 mmol, specifically at 25 mmol (0026 and Table 2). Lopez teaches the solution with adenosine at a concentration of 1-10 mmol specifically at 5 mmol (0026 and Table 2).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 6 and 7 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lopez in view of Jochmans (as applied to claims 1, 3, 10-12, and 15-18 above), and in further view of Fontes et al. (US 2015/0230453 A1) (ref. of record).
The teachings of Lopez and Jochmans can be found in the previous rejection above.
Lopez is silent as where the perfusing is continuous or pulsatile as recited in claims 6 and 7, respectively. However, Fontes teaches a similar method of exposing an organ to be transplanted to an aqueous solution (0002 and 0008). Fontes teaches the method where the exposing of the organ to the aqueous solution is by perfusing (0007-0008). Fontes further teaches the perfusion can be pulsatile or continuous to mimic either arterial blood flow or venous blood flow (0052). Accordingly at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Lopez so that the perfusion of the organ was either continuous or pulsatile for the benefit of mimicking the appropriate blood flow conditions for the organ as taught by Fontes. It would have been obvious to one of ordinary skill in the art to modify the method of Lopez to use known perfusion techniques in the art as demonstrated by Fontes. One of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Lopez, since continuous and pulsatile perfusion was known in the art in methods of exposing organs intended for transplantation to an aqueous solution to preserve the organ as taught by Fontes.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 13 and 17 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lopez in view of Jochmans (as applied to claims 1, 3, 10-12, and 15-18 above), and in further view of Ostróżka-Cieślik et al. (Acta Biochimica Polonica, 2018) (ref. of record) as evidenced by Nydegger et al. (Transplant Immunology, 2002) (ref. of record).
The teachings of Lopez and Jochmans can be found in the previous rejection above.
Lopez does not teach the method where the aqueous solution contains zinc ions at a concentration between 0.08-0.210 mmol.L-1 as recited in claim 13. However, Ostróżka-Cieślik teaches organ preservation solutions which are modified to include micronutrients to help improve the function of the organs when stored and where the micronutrient is zinc. Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include zinc in the aqueous composition for the benefit of improving the function of the organ as taught by Ostróżka-Cieślik. It would have been obvious to one of ordinary skill in the art to include zinc in the aqueous solution for preserving and rinsing an organ of Lopez, since it was known in the art to be included in such solutions for the same purpose as taught by Ostróżka-Cieślik. For this reason as well, one of ordinary skill in the art would have had a reasonable expectation of success in including zinc in the aqueous solution of Lopez.
Although Ostróżka-Cieślik is silent with respect to the concentration of zinc in the aqueous solution, one of ordinary skill in the art would recognize that the concentration of zinc is a result effective variable and that the amount of zinc would be matter of routine optimization depending on such factors as the organ being preserved. Furthermore, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
Lopez does not teach the method where the aqueous solution contains mannitol at a concentration between 40-80 mmol.L-1 as recited in claim 17, or where the aqueous solution contains mannitol at a concentration between 40-80 mmol.L-1 and histidine at a concentration between 25-35 mmol.L-1 as recited in claim 17. However, Ostróżka-Cieślik teaches organ preservation solution, Celsior, intended for the storage of thoracic organs such as hearts, lungs and organs of the abdominal cavity such as kidneys, livers and pancreas under hypothermic conditions and which contains mannitol as an antiedematous substance and histidine as a free radical scavenger (pg. 10 Col. 2 last para.). Celsior contains 60 mmol mannitol and 30 mM histidine as evidenced by Nydegger (Table 2). Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include mannitol and histidine in the aqueous composition for the benefit of acting as an antiedematous substance and as a free radical scavenger, respectively, as taught by Ostróżka-Cieślik. It would have been obvious to one of ordinary skill in the art to include mannitol and histidine in the aqueous solution for preserving and rinsing an organ of Lopez, since these were known in the art to be included in such solutions for the same purpose as taught by Ostróżka-Cieślik. For this reason as well, one of ordinary skill in the art would have had a reasonable expectation of success in including mannitol and histidine in the aqueous solution of Lopez.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 14 is rejected under 35 U.S.C. 103(a) as being unpatentable over Lopez in view of Jochmans (as applied to claims 1, 3, 10-12, and 15-18 above), and in further view of Li et al. (Journal of Transplantation, 2012) (ref. of record).
The teachings of Lopez and Jochmans can be found in the previous rejection above.
Lopez does not teach the method where the aqueous solution contains nitrite ions at a concentration between 5-100 nmol.L-1 as recited in claim 14. However, Li teaches a method of preserving organs for transplantation where the aqueous solution is supplemented with nitrite (abstract and pg. 2 Col. 1 para. 1). Li further teaches that the nitrite supplementation protected liver hepatocytes from apoptosis post-transplantation (abstract and pg. 2 Col. 1 para. 1). Li teaches the method where 0.25-1000 µM is used, and specifically teaches embodiments of the method using concentrations of 25 µM and 250 µM (25,000-250,000 nmol). Li notes that the protective effects of nitrite were dose dependent (pg. 4 Col. 1 para. 3).
Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include nitrite in the aqueous composition for the benefit of protecting the cells from apoptosis as taught by Li. It would have been obvious to one of ordinary skill in the art to include nitrite in the aqueous solution for preserving and rinsing an organ of Lopez, since it was known in the art to be included in such solutions for the same purpose as taught by Li. For this reason as well, one of ordinary skill in the art would have had a reasonable expectation of success in including nitrite in the aqueous solution of Lopez.
Although Li does not teach the claimed range of nitrite as recited in claim 14, one of ordinary skill in the art would recognize that the concentration of nitrite is a result effective variable as evidenced by Li and that the amount of nitrite would be matter of routine optimization depending on such factors as the organ being preserved and environmental conditions of the organ. Furthermore, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 13, 14, 17, and 19-21 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lopez in view of Jochmans (as applied to claims 1, 3, 10-12, and 15-18 above), and in further view of Ostróżka-Cieślik et al. (Acta Biochimica Polonica, 2018) (ref. of record) as evidenced by Nydegger et al. (Transplant Immunology, 2002) (ref. of record) and Li et al. (Journal of Transplantation, 2012) (ref. of record).
The teachings of Lopez and Jochmans can be found in the previous rejection above.
Lopez does not teach the method where the aqueous solution contains zinc ions at a concentration between 0.08-0.210 mmol.L-1 as recited in claim 13, or zinc ions at a concentration of 0.191 mmol.L-1 as recited in claims 19-21. However, Ostróżka-Cieślik teaches organ preservation solutions which are modified to include micronutrients to help improve the function of the organs when stored and where the micronutrient is zinc. Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include zinc in the aqueous composition for the benefit of improving the function of the organ as taught by Ostróżka-Cieślik. It would have been obvious to one of ordinary skill in the art to include zinc in the aqueous solution for preserving and rinsing an organ of Lopez, since it was known in the art to be included in such solutions for the same purpose as taught by Ostróżka-Cieślik. For this reason as well, one of ordinary skill in the art would have had a reasonable expectation of success in including zinc in the aqueous solution of Lopez.
Although Ostróżka-Cieślik is silent with respect to the concentration of zinc in the aqueous solution, one of ordinary skill in the art would recognize that the concentration of zinc is a result effective variable and that the amount of zinc would be matter of routine optimization depending on such factors as the organ being preserved. Furthermore, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
Lopez does not teach the method where the aqueous solution contains mannitol at a concentration between 40-80 mmol.L-1 as recited in claim 17, where the aqueous solution contains mannitol at a concentration between 40-80 mmol.L-1 and histidine at a concentration between 25-35 mmol.L-1 as recited in claim 17, where the aqueous solution contains mannitol at a concentration of 60 mmol.L-1 as recited in claim 20, or where the aqueous solution contains mannitol at a concentration of 60 mmol.L-1 and histidine at a concentration of 30 mmol.L-1 as recited in claim 21. However, Ostróżka-Cieślik teaches organ preservation solution, Celsior, intended for the storage of thoracic organs such as hearts, lungs and organs of the abdominal cavity such as kidneys, livers and pancreas under hypothermic conditions and which contains mannitol as an antiedematous substance and histidine as a free radical scavenger (pg. 10 Col. 2 last para.). Celsior contains 60 mmol mannitol and 30 mM histidine as evidenced by Nydegger (Table 2). Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include mannitol and histidine in the aqueous composition for the benefit of acting as an antiedematous substance and as a free radical scavenger, respectively, as taught by Ostróżka-Cieślik. It would have been obvious to one of ordinary skill in the art to include mannitol and histidine in the aqueous solution for preserving and rinsing an organ of Lopez, since these were known in the art to be included in such solutions for the same purpose as taught by Ostróżka-Cieślik. For this reason as well, one of ordinary skill in the art would have had a reasonable expectation of success in including mannitol and histidine in the aqueous solution of Lopez.
Lopez does not teach the method where the aqueous solution contains nitrite ions at a concentration between 5-100 nmol.L-1 as recited in claim 14, or at a concentration of 50 nmol.L-1 as recited in claims 19-21. However, Li teaches a method of preserving organs for transplantation where the aqueous solution is supplemented with nitrite (abstract and pg. 2 Col. 1 para. 1). Li further teaches that the nitrite supplementation protected liver hepatocytes from apoptosis post-transplantation (abstract and pg. 2 Col. 1 para. 1). Li teaches the method where 0.25-1000 µM is used, and specifically teaches embodiments of the method using concentrations of 25 µM and 250 µM (25,000-250,000 nmol). Li notes that the protective effects of nitrite were dose dependent (pg. 4 Col. 1 para. 3).
Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include nitrite in the aqueous composition for the benefit of protecting the cells from apoptosis as taught by Li. It would have been obvious to one of ordinary skill in the art to include nitrite in the aqueous solution for preserving and rinsing an organ of Lopez, since it was known in the art to be included in such solutions for the same purpose as taught by Li. For this reason as well, one of ordinary skill in the art would have had a reasonable expectation of success in including nitrite in the aqueous solution of Lopez.
Although Li does not teach the claimed range and concentration of nitrite as recited in claims 14 and 19-21, one of ordinary skill in the art would recognize that the concentration of nitrite is a result effective variable as evidenced by Li and that the amount of nitrite would be matter of routine optimization depending on such factors as the organ being preserved and environmental conditions of the organ. Furthermore, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 22 and 23 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lopez in view of Jochmans (as applied to claims 1, 3, 10-12, and 15-18 above), and in further view of Olausson (US 2022/0183272 A1, priority to Apr. 12, 2019) and Heron (EP 1997374 A2) (EPO machine translation).
The teachings of Lopez and Jochmans can be found in the previous rejection above.
Lopez does not explicitly teach the step of exposing further comprising a reconditioning of the organ in the aqueous solution as recited in claim 22 and where the aqueous solution is at a temperature between 2 to 10°C as recited in claim 23. However, Olausson teaches reconditioning organs after harvesting so that there are more organs available for transplantations (0009, 0058 and 0073). Olausson teaches that during perfusion the chemistry of the kidney is restored and toxic products are removed (0117). In further support, Heron teaches a method preparing an organ for transplantation with conditioning the organ for transplantation (0008 and 0011). Heron teaches the conditioning is performed by the steps of rinsing and preserving the organ in the solution (0008).
Accordingly, at the effective time of filing one of ordinary skill in the art would have been motivated to modify the method of Lopez to include a step of reconditioning the organ for the benefit of obtaining more organs available for transplantation as taught by Olausson. It would have been obvious to one of ordinary skill in the art to include a step of reconditioning the organ at a temperature between 2 to 10°C in the method of Lopez, since reconditioning and conditioning organs in the preservation solution was known in the art and within the claimed temperature as taught by Olausson and Heron. For these reasons as well, one of ordinary skill in the art would have had a reasonable expectation of success a step of reconditioning the organ where the aqueous solution is at a temperature between 2 to 10°C in the method of Lopez. Additionally, it is noted the teachings of Heron and Olausson suggest that reconditioning might be inherent to practicing the method of Lopez, since the reconditioning steps involve perfusion of the organ with an aqueous solution and there is no clear definition of what reconditioning encompasses.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Sept. 17, 2025 have been fully considered but they are not persuasive.
Applicant notes that the Lopez reference is assigned to and owned by the Applicant and, therefore, they have a thorough knowledge of the concepts and procedures described (Remarks pg. 6-7 bridging para.). This is acknowledged.
With respect to the rejections under 35 U.S.C. § 102, Applicant argues that a person skilled in the art would recognize the distinction between static and dynamic preservation, where in static preservation there is little or no alteration of the physical and chemical surroundings and in dynamic preservation the preservation solution is continuously circulated through the organ’s vessels without renewal (Remarks pg. 7 para. 2). This argument is not being disputed and it is noted that the differences between static and dynamic preservation are well known in the art.
Applicant argues that Lopez teaches all organs were perfused with KREPS solution for evaluation and static preservation was performed before the dynamic preservation in KREPS-Henseleit bicarbonate solution (KREPS) only and not the inventive solution of Lopez as disclosed in Table 2 (Remarks pg. 7 para. 3-4). However, this argument was not found to be persuasive, since the Lopez does not clearly state in the document that all of the organs were perfused with KREPS after static preservation. For instance, in para. 0034, it is unclear from the text if the technique used in the Examples requires perfusion with KREPS-Henseleit bicarbonate solution or whether this is an exemplary artificial solution used in known techniques. This is especially unclear given the prior paragraph states that the performance of the inventive solution is being compared with the Belzer-Viaspan solution in para. 0033. Additionally, Lopez states perfusing liver with their inventive solution in para. 0055. Even if Lopez does not clearly teach perfusion of their inventive solution, it would have been obvious to one of ordinary skill in the art to perfuse with preservation solution of Lopez, since perfusion or dynamic preservation was well-known at the effect time of filing as taught by Jochmans and explained in the new rejections under 35 U.S.C. § 103.
Applicant argues there is no motivation or suggestion in Lopez to use the aqueous solution of Table 2 for dynamic perfusion (Remarks pg. 8 para. 1). However, this argument was not found to be persuasive as explained in the new rejections under 35 U.S.C. § 103. Jochmans provides motivation for the use of perfusion in Lopez, if Lopez does not anticipate perfusion. Jochmans teaches dynamic preservation allows for optimizing organ preservation, for real-time graft viability assessment, and for a mode of delivering condition agents to repair damaged organs, thus improving organ quality and utilization (pg. 2546 Col. 1 para. 1).
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that Lopez does not teach rinsing and dynamic preservation of the organ in the claimed aqueous solution and instead teaches the use for static preservation only (Remarks pg. 8 para. 4). This argument was address in response to the arguments in response to the rejections under 35 U.S.C. § 102.
Applicant argues there is no motivation or suggestion in Lopez to modify its static solution for dynamic preservation and these solutions are significantly different (Remarks pg. 8-9 bridging para.). However, this argument was not found to be persuasive, as stated in the new rejections, Jochmans teaches the benefits of dynamic preservation preserving organs for transplantation including improved organ quality and utilization (abstract and pg. 2546 Col. 1 para. 1). Additionally, Lopez teaches the desire for one solution for preserving organs (0006-0015). Therefore, it would have been obvious to one of ordinary skill in art to use the preservation solution taught by Lopez in dynamic preservation, since Lopez teaches the desire for one solution and Jochmans teaches the benefits of dynamic preservation.
Applicant argues that there is no connection between the solution in Lopez and the methods of Fontes, since Fontes describes dynamic preservation including pulsatile or continuous preservation and Lopez only teaches static preservation for the solution (Remarks pg. 9 para. 1). Applicant argues that even if Lopez and Fontes were combined, Lopez only teaches KREPS-Henseleit bicarbonate solution for a perfusion solution (Remarks pg. 10 para. 2). However, this argument was not found to be persuasive, since as explained in the current rejections Lopez teaches dynamic preservation and teaches perfusion of livers with the inventive solution (0055). Additionally, even if Lopez did not teach dynamic preservation with the inventive solution, it would have been obvious to modify Lopez to include dynamic preservation with the inventive solution in view of the benefits taught by Jochmans.
Applicant argues the combination of Lopez and Ostrozka-Cieslik is improper, since there is no motivation in Lopez to include additional components like zinc, mannitol or histidine for a static preservation solution designed for cold storage with minimal metabolic activity in the micronutrients listed in the review article, Ostrozka-Cieslik (Remarks pg. 9 para. 4-5). However, this argument was not found to be persuasive, since the motivation to combine is found in Ostróżka-Cieślik. Ostróżka-Cieślik teaches organ preservation solutions which are modified to include micronutrients to help improve the function of the organs when stored and where the micronutrient is zinc. It is maintained that one of ordinary skill in the art would have been motivated to modify the method of Lopez to include zinc in the aqueous composition for the benefit of improving the function of the organ as taught by Ostróżka-Cieślik.
Applicant argues that there is no reason for adding the nitrate taught by Li for reducing cold ischemia-reperfusion injury and protecting hepatocytes from apoptosis post-transplantation to the solution used in the method of Lopez (Remarks pg. 10 para. 1). Applicant further argues hindsight reconstruction was used in combining Lopez with Li to arrive at the claimed invention (Remarks pg. 10 para. 2). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, Li provides motivation to modify the method of Lopez. Li teaches that the nitrite supplementation protected liver hepatocytes from apoptosis post-transplantation (abstract and pg. 2 Col. 1 para. 1). Therefore, it is maintained that one of ordinary skill in the art would have been motivated to modify the method of Lopez to include nitrite in the aqueous composition or inventive solution for the benefit of protecting the cells from apoptosis as taught by Li.
Applicant argues that Olausson is different from Lopez and the claimed invention is directed to organ preservation which is different from organ regeneration (Remarks pg. 10 para. 4). However, this argument was not found to be persuasive, since both Lopez and Olausson are directed to preserving organs for transplantation. Olausson teaches their “invention relates to harvesting organs and preservation and evaluation of organs”. Even though, Olausson focuses on reconditioning organs after harvesting and a method preparing an organ for transplantation with conditioning the organ for transplantation (0008-0009, 0011, 0058 and 0073) these methods are relevant to the claimed preservation method and the preservation method of Lopez.
In summary, Applicant argues that Lopez does not teach or suggest dynamic preservation using the claimed solution and perfusion does not correspond to dynamic preservation (Remarks pg. 10 last para.). However, this argument was not found to be persuasive, since Lopez does teach rinsing and dynamic preservation of the organ in the aqueous solution as explained in the rejections (0001-0003, 0007, 0028 and 0055). Additionally, the teachings in Jochmans makes obvious dynamic preservation of organs and defines it as perfusion (pg. 2546 Col. 1 para. 2). Furthermore, the instant specification describes dynamic preservation of an organ as continuous infusion and states that it can be called dynamic perfusion, see 0001 and 0027 of published application, and Lopez teaches perfusing the organ (0035-0038 and 0045). The specification further describes dynamic preservation requiring a perfusion machine to control the circulation of a perfusion (0027-0028 of published application). Therefore, it is reasonable to assume that the perfusion of the organs described in Lopez is dynamic preservation.
Response to Evidentiary Declaration under 37 CFR §1.132
The declaration of M. Alexandre Lopez, Ph.D filed on Sept. 17, 2025 under 37 CFR §1.132 has been considered but is ineffective to overcome the rejections of the claims under 35 U.S.C. §102 and 35 U.S.C. §103 over Lopez.
Dr. Lopez states that he has thorough knowledge of the Lopez reference, as it is assigned to and owned by IGL (Declaration para. 9).
Dr. Lopez states that all of the dynamic perfusion performed in Lopez is performed using the KREPS perfusion buffer and not Lopez’s inventive solution as stated in 0033-0038, 0045 and shown in Table 3 of Lopez (Declaration para. 10-13). Dr. Lopez also states that there is nothing in Lopez to point one to use their inventive solution for dynamic perfusion (Declaration para. 14). However, these statements were not persuasive to overcome the rejections of record. The reference, Lopez, teaches comparing the perfusion of the different solutions in livers including the including the inventive solution of Group A in para. 0055. Additionally, even though the experiments may have been carried out where perfusion was only performed with the KREPS perfusion buffer in Lopez this is not readily apparent when reading the document. As stated previously, even if Lopez does not clearly teach perfusion of their inventive solution, it still would have been obvious to one of ordinary skill in the art to perfuse with preservation solution of Lopez, since perfusion or dynamic preservation was well-known at the effect time of filing as taught by Jochmans and explained in the new rejections under 35 U.S.C. § 103.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632