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 .
Claims 1-20, of record 6/13/2024, are pending and subject to prosecution.
Priority
The instant application is a national stage entry of PCT/NL2022/050751 (filed 12/22/2022). Acknowledgement is made of the applicant’s claim for foreign priority to EPO application 21217091.4 (filed 12/22/2021).
Specification
The use of the terms Liver Assist, iSTAT, Simcyp, Acquity UPLC, and Q Exactive Orbitrap, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claim 15 recites the limitation “further comprising packaging the one or more purified compounds of interest”. The term “packaging” is not defined by the instant specification. The broadest reasonable interpretation of “packaging” is therefore considered to encompass enclosure in a wrapper or container.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 12, the term “preferably” renders the claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP 2173.05(d).
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.
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Curtis et al. (US 20080286747 A1), of record in IDS dated 6/14/2024, in view of Chung et al. (Artificial Organs, 2013) and Lösel et al. (Archiv fur Tierzucht, 2013).
Regarding claims 1-5, 7, 10, 12-14, and 19-20: Curtis et al. teach ex vivo methods for substance testing using tissues and/or organs such as the liver or kidney (See Abstract and ¶0038). The tissues and/or organs can be perfused in order to assess metabolism of substances such as drug candidates and metabolites thereof (which read on “precursor or… one or more compounds of interest” and “precursor is a compound that is metabolized”) (See ¶0008, 0018, 0025-0026, and 0140). The perfusate can be analyzed by metabolite profiling via extraction (which reads on “extraction using an organic solvent”) and HPLC (which reads on “purification”, “chromatography”, and “column chromatography”) (See ¶0156 and 0163). Perfusion is preferably performed under physiological temperature (which reads on “normothermic”) and oxygenation (which reads on “continuously oxygenated”) (See ¶0013). Dosing of the liver preferably comprises adding about 50 mg of test compound to the perfusate over time (See ¶0151). Delivery of the test compounds can take place at physiological flow rates (which reads on “continuously perfused”) over about 240 min (which reads on “at least 4 hours”) (See ¶0140 and 0151-0152). Curtis et al. teach that perfusate flow occurs through the portal vein and hepatic artery as inlets (See ¶0141-0143).
Curtis et al. do not expressly teach the organs as being obtained from a slaughterhouse, liver weight, or the concurrent perfusion of a kidney.
Chung et al. teach a multiorgan ex vivo perfusion model comprising a porcine liver and kidney (See Abstract and fig. 1). Perfusion of the kidney occurred by cannulation of the renal artery (See page 458, col. 2, ¶1 and 3; page 459, col. 1, ¶1; and fig. 1). The organs were obtained from domestic pigs weighing 45-60 kg (See page 458, col. 1, full ¶2).
Lösel et al. teach that a domestic pig weighing approximately 47 kg has an average liver weight of approximately 1.1 kg (which reads on “at least about 250 gr.”) (See page 769, full ¶2 and table 1), which suggests that the pig livers of Chung et al. would weight similarly.
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Curtis et al. to comprise the use of a porcine liver and kidney. One would have been motivated to make this modification because Curtis et al. teach that liver perfusate can be used for kidney perfusion in order to resolve the renal handling or further metabolism of hepatic metabolites (See ¶0173), and because Chung et al. teach that the use of porcine organs has no ethical restrictions as the animals are destined for the food chain process and are already dead at the time of organ harvesting (which reads on “obtained from a slaughterhouse”) (See page 465, col, 1, ¶1). While Chung et al. do not teach the liver and kidney perfused in series, such a modification could be readily made in order to recapitulate physiological drug metabolism.
Regarding claim 6: Following the discussion of claims 1-5, 7, 10, 12-14, and 19-20: Curtis et al. do not expressly teach perfusion of at least 100 mg of a test compound. However, Curtis et al. teach that a compound can be tested in the liver using repeated pulse dosing (See ¶0166), which would read on “at least 100 mg” for a preferred 50 mg dose.
Regarding claims 8 and 17: Following the discussion of claims 1-5, 7, 10, 12-14, and 19-20, Curtis et al. teach that the perfusate preferably comprises erythrocytes (which reads on “an oxygen carrier” and “red blood cells”) in a physiologically-acceptable medical fluid (See ¶0048).
Regarding claims 9 and 18: Following the discussion of claims 1-5, 7, 10, 12-14, and 19-20, Curtis et al. teach that the perfusate can comprise bile acids such as glycocholate (which reads on “cholate”) (See ¶0048, 0111, and 0144).
Regarding claims 11 and 16: Following the discussion of claims 1-5, 7, 10, 12-14, and 19-20, Curtis et al. teach that the gall bladder can remain attached to the liver for perfusion (which reads on “an organ system further comprising a gall bladder”) (See ¶0156). Curtis et al. also teach that metabolic studies can be used to assess metabolite identification and quantification and the partitioning of metabolites between plasma and bile (which reads on “purified from bile”) (See ¶0166).
Regarding claim 15: Following the discussion of claims 1-5, 7, 10, 12-14, and 19-20, Curtis et al. do not expressly teach packaging of purified drug metabolites. However, Curtis et al. teach that specific metabolites from liver perfusion tests may be characterized in separate studies (See ¶0140), which implies a step wherein the metabolites are packaged for subsequent testing.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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