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 .
Status of the claims
The preliminary amendment filed 06/15/23 is acknowledged and has been entered. Claims 1 and 3-13 have been amended. Claim 2 has been canceled. New claims 14-18 have been added. Accordingly, claims 1 and 3-18 are pending and under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825). A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system.
In the instant specification there is no section entitled Brief Description of the Drawings.
Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 10 and 12-13 are objected to because of the following informalities: Claim 10 is objected to because of the use of an acronym: i.e. PNF. Although the term may have art-recognized meaning, the term should be defined in their first instance.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-13 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and/or to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
The is directed to a naturally occurring correlation between the levels of alamin in a subject after solid organ transplantation and performing retransplantation.
Step 2A, Prong 2
The additional elements of determining the level of at least one alarmin does not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Also, with respect to the recitation “determining the level of at least one alarmin in a sample..”. The “determining” statement at best articulates the judicial exception, amounting only to a general instruction to apply or use the judicial exception. This could read on mental activity being performed solely in a practitioner’ head, e.g. A mental appreciation of the level of the alarmin in a subject having undergone a solid organ transplantation. No active method steps are invoked or clearly required; the “determining” statements do not include any activity that would constitute a practical application, i.e. steps that apply, rely on or use the natural principle in a manner such that the claims amount to significantly more that the natural principal itself.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims are recited with a high level of generality and do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. (the active method steps/limitations recited in addition to the judicial exceptions themselves) and do not add significantly more to the judicial exception(s).
As shown by the art below it is well known routine and conventional in the art to obtain a sample from a subject that has undergone a solid organ transplant and to detect at least one alarmin.
With respect to the “performing a retransplantation in a subject identified as having a high level of the at least one alarmin, compared to a predetermined reference value” as recited in claim 1. Although the claim invokes administering a retransplant to the subject the claim as currently recited allows for a scenario wherein low levels are determined. As clearly indicated in claim 10 which recited “conversely low levels….”. This shows that claim 1 is open to both the determination of higher and lower levels and thus provides an embodiment wherein no retransplant would be performed.
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
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.
Written Description
Claims 1, 3-13 and 18 are 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 claim(s) contains 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.
The claims are directed to methods of determining assessing I/R injury severity and/or a risk of early allograft dysfunction of determining levels of any and all alarmins after any and all solid organ transplants and using the levels of the any and all alarmins from any and all samples from any and all subjects and correlating the results I/R severity and/or risk of early allograft dysfunction or determining levels after transplantation. The limitation 'patient’ represents a genus and encompasses human and non-human including mouse, monkey, dog, rat, pig, insects, kangaroo, horse, canine and snake to name a few. The limitation ‘sample’ represents a genus and encompasses tears, semen, urine, brain tissue, liver tissue, synovial fluid, peritoneal fluid, sputum, diarrhea or vomit. The limitation ‘solid organ transplant” represents a genus and encompasses heart, lung, pancreas, skin, uterus, bone, cartilage, stomach, testes, thymus, thyroid, trachea and urethra to name a few. The limitation ‘alarmin’ represents a genus and encompasses alpha-defensins, uric acid crystals, beta-defensins, cathelicin, granulysin, heat shock proteins, S200A8, S100A9 and adenosine triphosphate to name a few. However, there is inadequate written description in the instant specification for a method of such broad scope as claimed currently.
In order to fulfill the written description requirements set forth under 35 U.S.C § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, each member correlated with the requisite function, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicants have possession the claimed invention. Applicants have not described and established structure-function correlation for a representative number of species within the broad genus of at least the recited ‘patient’, ‘sample’, ‘solid organ transplant’ and “alarmin” such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the full scope of the claimed invention at the time the application was filed.
The purpose of the written description requirement is ‘to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.’ In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. When there is substantial structural variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
A review of the instant specification indicates the following. The specification on page 6 discloses that the term IL-44 has its general meaning in the art and refers to the human IL-33. The specification on pages 12-13 and the figures of the specification discloses the detection of IL-33 and HMGB1 in serum samples from humans patients immediately after liver transplantation and the comparison of the levels to that of healthy controls and a correlation with I/R. The examples in the specification appear to be directed the patients being a human and the sample as blood or serum for the detection of IL-33 and HMGB1 levels and a specific correlation with I/R. The specification does not provide data, testing or examples with a showing that any all and all samples from any and all patients provide for any and all alarmin biomarkers and that all the biomarkers are produced, provided or correlated with any and all organ transplants. The only data in the specification is limited to the detection of IL-33 and HMGB1 levels in human patients that have undergone a liver transplant. The specification does not provide any data, results or evidence that these two very specific biomarkers found in the blood of human patients that have undergone a liver transplant are expected to be or are at levels in all sample from all patients that have undergone any type of solid organ transplant. Also, Torzewski et al, (Hindawl Publishing Corporation, Mediators of Inflammation, Vol 2014, Articles ID 683598, pages 1-7) teaches for example that CRP (biomarker) is an acute phase reactant in humans but not an acute phase reactant in a mouse (e.g. page 1). Van Der Vekens et al., (Cardiovascular Endocrinology, 2013, Vol 2, No. 4,pages 67-76) teaches that markers between human and equine show important species differences, which can be explained by variations in physiology or pathophysiology and also teaches pathological differences in the species (e.g. abstract).
The only examples utilized in the specification appears to be limited to blood or serum from a human patient and the measurement of IL-33 and HMGB1 wherein the human patient has undergone a liver transplant and can be correlated with I/R injury severity and/or a risk of early allograft dysfunction EAD after liver transplantation. The specification does not disclose any and all samples comprise the any and all alarmin biomarkers in any and all patients having undergone any type of solid organ transplantation. Further, the specification does not disclose that IL-33 and HMGB1 which appear in blood or serum also appear in samples such as tears, diarrhea, sputum, plural fluid etc. or that such biomarkers would be expected to be shed, excreted into or found in these samples and at levels after any and all solid organ transplants which are correlated I/R injury severity. As stated supra the specification appears to be limited to blood or serum from a human patient for the detection and measurement of IL-33 and HMGB1 wherein the human patient has undergone a liver transplantation.
The specification also fails to provide for a correlation of the recited biomarkers in all subjects such as dogs, cats, cows, monkey, horse, rabbit squirrel and mice (as shown supra by Torzewski and Van Der Vekens different species of mammal have different expression of biomarkers and do not correlate to the same condition/disease) The specification also fails to provide that the recited biomarkers exist in samples such as saliva, tears, sputum, CSF or diarrhea or that a correlation of these biomarkers exist in such subjects at levels which are correlated with any and all endoscopically active gastrointestinal diseases. Further, it is not well known in the art that these samples provide for the recited biomarkers and that a correlation exists between such biomarkers in the samples to any and all solid organ transplantations. The examples in the specification appear to be limited to blood or serum from a human patient and the measurement of IL-33 and HMGB1 wherein the human patient has undergone a liver transplant and can be correlated with I/R injury severity and/or a risk of early allograft dysfunction EAD after liver transplantation or show a correlation with liver transplantation. The purpose of the ‘written description; requirement is broader than to merely explain how to ‘make and use’, Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.
It must be noted that "[t]he applicant must . . . convey to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention." Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir.1991). The invention, is for purposes of the ‘written description’ inquiry, whatever is now claimed.” See page 1117. The specification does not describe the claimed embodiments in sufficient detail to convey to a person skilled in the art that Applicants were in possession of the full scope of the claimed invention at the time of filing. The Written Description Guidelines state: There is an inverse correlation between the level of predictability in the art and the amount of disclosure necessary to satisfy the written description requirement. For example, if there is a well-established correlation between the structure and function in the art, one skilled in the art will be able to reasonably predict the complete structure of the claimed invention from its function. Furthermore, the written description provision of 35 U.S.C § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, ‘Written Description’ Requirement (66 FIR 1099-1111, January 5,2001) state, ‘[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention’ (Id. at 1104). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. Factual evidence of an actual reduction to practice has not been disclosed in the instant specification, nor has Applicant shown the invention was ‘ready for patenting’. The Guidelines further state, ‘[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus' (Id. at 1106). For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. Instant claims are viewed as not meeting the written description provision of 35 U.S.C § 112, first paragraph. The specification fails to disclose the detection of any and all alarmin biomarkers in any and all biological samples from any and all patients and correlated with I/R injury severity and/or a risk of early allograft dysfunction EAD after liver transplantation or show a correlation with all solid organ transplantations.
Scope of Enablement
Claims 1, 3-13 and 18 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for methods of transplanting a liver into a human transplant patient and detecting the levels of IL-33 and HMGB1 in a blood or serum sample from the patient and performing a liver retransplant. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Enablement requires that the specification teach those in the art to make and use the invention without undue experimentation. The factors that must be considered in determining undue experimentation are set forth in In re Wands USPTQ2d 14000. Factors to be considered in determining whether a disclosure would require undue experimentation include (1) the nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the quantity of experimentation necessary, (7) the relative skill of those in the art, and (8) the breadth of the claims.
The claims are directed to methods of determining assessing I/R injury severity and/or a risk of early allograft dysfunction of determining levels of any and all alarmins after any and all solid organ transplants and using the levels of the any and all alarmins from any and all samples from any and all subjects and correlating the results I/R severity and/or risk of early allograft dysfunction or determining levels after transplantation.
A review of the instant specification indicates the following. The specification on page 6 discloses that the term IL-44 has its general meaning in the art and refers to the human IL-33. The specification on pages 12-13 and the figures of the specification discloses the detection of IL-33 and HMGB1 in serum samples from humans patients immediately after liver transplantation and the comparison of the levels to that of healthy controls and a correlation with I/R. The examples in the specification appear to be directed the patients being a human and the sample as blood or serum for the detection of IL-33 and HMGB1 levels and a specific correlation with I/R. The specification does not provide data, testing or examples with a showing that any all and all samples from any and all patients provide for any and all alarmin biomarkers and that all the biomarkers are produced, provided or correlated with any and all organ transplants. The only data in the specification is limited to the detection of IL-33 and HMGB1 levels in human patients that have undergone a liver transplant. The specification does not provide any data, results or evidence that these two very specific biomarkers found in the blood of human patients that have undergone a liver transplant are expected to be or are at levels in all sample from all patients that have undergone any type of solid organ transplant. Also, Torzewski et al, (Hindawl Publishing Corporation, Mediators of Inflammation, Vol 2014, Articles ID 683598, pages 1-7) teaches for example that CRP (biomarker) is an acute phase reactant in humans but not an acute phase reactant in a mouse (e.g. page 1). Van Der Vekens et al., (Cardiovascular Endocrinology, 2013, Vol 2, No. 4,pages 67-76) teaches that markers between human and equine show important species differences, which can be explained by variations in physiology or pathophysiology and also teaches pathological differences in the species (e.g. abstract).
The only examples utilized in the specification appears to be limited to blood or serum from a human patient and the measurement of IL-33 and HMGB1 wherein the human patient has undergone a liver transplant and can be correlated with I/R injury severity and/or a risk of early allograft dysfunction EAD after liver transplantation. The specification does not disclose any and all samples comprise the any and all alarmin biomarkers in any and all patients having undergone any type of solid organ transplantation. Further, the specification does not disclose that IL-33 and HMGB1 which appear in blood or serum also appear in samples such as tears, diarrhea, sputum, plural fluid etc. or that such biomarkers would be expected to be shed, excreted into or found in these samples and at levels after any and all solid organ transplants which are correlated I/R injury severity. As stated supra the specification appears to be limited to blood or serum from a human patient for the detection and measurement of IL-33 and HMGB1 wherein the human patient has undergone a liver transplantation.
The specification also fails to provide for a correlation of the recited biomarkers in all subjects such as dogs, cats, cows, monkey, horse, rabbit squirrel and mice (as shown supra by Torzewski and Van Der Vekens different species of mammal have different expression of biomarkers and do not correlate to the same condition/disease) The specification also fails to provide that the recited biomarkers exist in samples such as saliva, tears, sputum, CSF or diarrhea or that a correlation of these biomarkers exist in such subjects at levels which are correlated with any and all endoscopically active gastrointestinal diseases. Further, it is not well known in the art that these samples provide for the recited biomarkers and that a correlation exists between such biomarkers in the samples to any and all solid organ transplantations. The examples in the specification appear to be limited to blood or serum from a human patient and the measurement of IL-33 and HMGB1 wherein the human patient has undergone a liver transplant and can be correlated with I/R injury severity and/or a risk of early allograft dysfunction EAD after liver transplantation or show a correlation with liver transplantation. Thus, for the reasons stated above one of skill in the art cannot practice the claimed invention without undue experimentation.
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.
Claims 1 and 3-18 are 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.
Claim 1, line 4 is indefinite in reciting “determining the level of at least one alarmin in a sample” because the term “determining” appears to intend a mental step; hence, it is unclear if applicant actually intends a positive active method step in the claim. It is suggested but not required to delete the term “determining” and replace it with --detecting--.
Claim 10 is vague and indefinite in reciting “and/or PNF” because claim 1 from which claim 10 depends does not require PNF” and thus by reciting “or PNF” causes confusion as to if the PNF is to replace the limitations of claim 10. Please clarify.
Claim 14, line 3 is indefinite in reciting “determining the level of at least one alarmin in a sample” because the term “determining” appears to intend a mental step; hence, it is unclear if applicant actually intends a positive active method step in the claim. It is suggested but not required to delete the term “determining” and replace it with --detecting--.
Claim 16, line 3 is indefinite in reciting “determining the level of at least one alarmin in a sample” because the term “determining” appears to intend a mental step; hence, it is unclear if applicant actually intends a positive active method step in the claim. It is suggested but not required to delete the term “determining” and replace it with --detecting--.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 10 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1 is directed to a method of assessing I/R injury severity and/or risk or EAD in a subject that has undergone a solid organ transplant and requires determining the level of at least one alarmin and performing a retransplantation. However, claim 10 provides for determining a lower level and when this occurs no retransplant occurs and thus claim 10 fails to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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.
Claims 14 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mehta et al (Journal of Surgical Research 70, 1997, pages 151-155).
Mehta et al discloses a method comprising transplanting a heart into a rat (e.g. abstract, pg 152). Mehta et al discloses detecting hsp70 (alarmin) in a sample from the rat (e.g. pgs 152, 154). Mehta et al discloses quantifying the hsp70 and determining a significantly greater value that that of a control (e.g. pg 154, Fig 4).
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.
NOTE: it is noted that the instant claims merely recite for assessing ischemia-reperfusion (I/R) injury severity and/or risk of early allograft dysfunction (EAD) in the preamble of the claim and that the body of the claim does not specifically correlate the levels with I/R or EAD.
Claims 1, 3, 5-11 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Thierry et al (PLOS ONE, Feb. 2014, vol 9, Issue 2, pages 1-10) (submitted in the IDS filed 06/15/23) in view of Zhao et al (EBioMedicine 28, 2018, pages 31-42) and Roozbeh et al (Experimental and Clinical Transplantation, November 2016, pages 1-6).
Thierry et al discloses a method comprising detecting the levels of HMGB1 and IL-33 in blood and urine samples from a human subject before (baseline predetermined) and after kidney transplant (e.g. abstract, pgs 2-5). Thierry et al discloses the measurement of the IL-33 and HMGB1 can be by enzyme linked immunosorbent assay (e.g. abstract, pg3). Thierry et al discloses that increased levels were positively correlated with cold ischemia time and that severity of tissue injury can be considered reliable indicator of cold ischemia and this data supports a close relationship between IL-33 release and kidney IRI (e.g. abstract, pgs 3 and 5). Thierry et al discloses that cold ischemia is associated with graft function and graft loss and thus the IL-33 could be used as a prognostic-indictor for such loss (e.g. page 8).
Thierry et al differs from the instant invention in failing to teach retransplant if the level is high compared to a predetermined reference.
Zhao et al teaches that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury and chronic hypoxia as well as subsequent fibrosis, Zhao et al teaches that IRI is also known to induce allograft dysfunction and acute rejection (e.g. abstract).
Roozbeh et al teaches that patients with failed kidney grafts need transplant as renal replacement therapy (e.g. page 1).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the method of the detection of graft loss (rejection)(severe injury) in the method Thierry et al because Thierry et al specifically teaches that cold ischemia is associated with graft function and graft loss and thus the IL-33 could be used as a prognostic-indictor for such loss and Zhao et al shows that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury and chronic hypoxia as well as subsequent fibrosis, Zhao et al teaches that IRI is also known to induce allograft dysfunction and acute rejection. Thus, one of ordinary skill in the art would apply the detection of IL-33 in subjects suspected of kidney graft loss in the method of Thierry et al and one would also incorporate renal transplant replacement such as taught by Roozbeh et al into the modified method of Thierry et al because Roozbeh et al teaches that patients with failed kidney grafts need a retransplant. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating graft loss detection and retransplant into the method of Thierry et al.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Thierry et al in view of Zhao et al and Roozbeh et al as applied to claims 1, 3, 5-11 and 14-18 above, and further in view of Wadei et al (Transplantation Direct, March 2018; 4, pages 1-7).
See above for the teachings of Thierry et al., Zhao et al and Roozbeh et al.
Thierry et al., Zhao et al and Roozbeh et al. differ from the instant invention in failing to teach the subject has undergone a liver transplant.
Wadei et al teaches that it is known in the art that subject may undergo both kidney and liver transplant and teaches that there is significant interplay between EAS, post-liver transplant renal recovery, and post-liver transplant outcomes (e.g. abstract, page 3-patient population and page 6).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate liver transplant subjects such as taught by Wadei et al into the modified method of Thierry et al because Wadei et al teaches a correlation of kidney and liver transplant with renal recover. Thus, absent evidence to the contrary one of ordinary skill in the art would have a reasonable expectation of success incorporating liver transplant subjects such as taught by Wadei et al into the modified method of Thierry et al.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Thierry et al in view of Zhao et al and Roozbeh et al as applied to claims 1, 3, 5-11 and 14-18 above, and further in view of Williams et al (JPM Vol 37, No. 1, Feb. 1997, pages 1-7).
See above for the teachings of Thierry et al., Zhao et al and Roozbeh et al.
Thierry et al., Zhao et al and Roozbeh et al. differ from the instant invention in failing to teach calculating a score to represent an estimation of severity an/or risk of EAD and/or PNF.
Williams et al teaches the characterization of renal ischemia-reperfusion injury and the calculation of a severity score of the kidneys to reflect the extent of kidney damage (e.g. page 5, Table 2 and Fig. 4).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the use of a score such as taught by Williams et al into the modified method of Thierry et al because both Thierry et al and Williams are concerned with renal ischemia reperfusion and Williams shows that providing a calculated score provides for a reflection of the extent of kidney damage. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating the use of a score such as taught by Williams et al into the modified method of Thierry et al.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Thierry et al in view of Zhao et al and Roozbeh et al as applied to claims 1, 3, 5-11 and 14-18 above, and further in view of Higgins et al (US 8,126,690).
See above for the teachings of Thierry et al., Zhao et al and Roozbeh et al.
Thierry et al., Zhao et al and Roozbeh et al. differ from the instant invention in failing to teach implementing an algorithm on data to give an output.
Higgins et al shows that it is known and conventional in the art to utilize algorithms to give output on a clinical condition (e.g. abstract). Further, by way of Applicant’s own disclosure on pages 11-12 of the current specification the use of algorithms are well known and conventional in the art.
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the use of algorithms such as taught by Higgins et al into the modified method of Thierry et al to produce data concerning the I/R injury severity because Higgins et al teaches that the use of algorithms are known and conventional and by way of Applicant’s own disclosure the use of algorithms is known. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating the use of algorithms such as taught by Higgins et al into the modified method of Thierry et al.
Conclusion
No claims are allowed.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678