DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of selected species (ethyl-β-D-glucuronide and ethyl-β-D-galactopyranoside, and an inflammatory reaction in response to a lesion or infection of the organism) in the reply filed on June 25, 2026 is acknowledged.
Claims Summary
Claim 1 is directed to a composition, and claim 9 is directed to a kit comprising a composition, both compositions comprising at least:
Ethyl-β-D-glucuronide wherein the ethyl part comprises at least one non-radioactive isotope; the specification discloses that ethyl-β-D-glucuronide targets the enzyme β -glucuronidase (see paragraph [0025] of the published application US-2024/0361317-A1), and
Ethyl-β-D-galactopyranoside wherein the ethyl part comprises at least one non-radioactive isotope; the specification discloses that ethyl-β-D-galactopyranoside targets the enzyme β-galactosidase (see paragraph [0027] of the published application US-2024/0361317-A1)
The specification discloses ethyl-β-D-glucuronide as:
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The specification discloses, as an example, D5-ethyl-β-D-glucuronide, which has the non-radioactive isotope deuterium (2D) as:
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The specification discloses ethyl-β-D-galactopyranoside as:
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The specification discloses, as an example, D2-ethyl-β-D-galactopyranoside, which has the non-radioactive isotope deuterium (2D) as:
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The intended use of the composition of claim 1 is as a diagnostic and/or prognostic agent. The intended use of the kit of claim 9 is for the diagnosis of an inflammatory reaction in response to a lesion or infection of the organism. Paragraph [0075] of the published application US-2024/0361317-A1 provides a non-limiting definition: “‘pathological conditions involving an inflammatory reaction in response to a lesion or infection of the organism’ denotes in particular cancers, pulmonary ARDS and fibrosis, or Parkinson’s disease”.
Claim 4 is directed to a method for diagnosing, in a subject, an inflammatory reaction in response to a lesion or infection of the organism, comprising:
Adding, in a biological sample of the subject, a composition as outlined above; the sample is plasma, among other choices (claim 8);
Measuring the amount of labeled ethanol released in the gas phase;
Comparing the values obtained in step b) with a corresponding standard control value; and
Deducing therefrom whether the subject is affected by an inflammatory reaction in response to a lesion or infection of the organism
The specification teaches that ethyl-β-D-glucuronide and ethyl-β-D-galactopyranoside (both having non-radioactive isotopes) act as probes. In injured tissues, they are selectively hydrolyzed when acted upon by their respective enzymes, β-D-glucuronidase and β-galactosidase, releasing ethanol isotopes that are detected (see paragraphs [0040]-[0041], [0150] and [0152] of the published application US-2024/0361317-A1).
Claim 5 is directed to a method for tracking the efficacy of a curative or preventative treatment of an inflammatory reaction in response to a lesion or infection of the organism, comprising:
Adding, in a biological sample of the subject at an instant t during said treatment, a composition as outlined above;
Measuring the amount of labeled ethanol released in the gas phase;
Comparing the values obtained in step b) with a corresponding standard control value and/or with a corresponding value obtained before the start of the treatment or at an instant t’ during the treatment which is prior to the instant t;
Deducing therefrom whether the treatment is effective; and
Optionally, repeating steps a) to d)
Claim 6 is directed to a method for tracking the course of an inflammatory reaction in response to a lesion or infection of the organism, comprising:
Adding, in a biological sample of the subject at an instant t1, a composition as outlined above;
Measuring the amount of labeled ethanol released in the gas phase for the sample at instant t1;
Adding, in the biological sample, at instant t2 separated in time from instant t1, the composition of step a);
Measuring the amount of labeled ethanol released in the gas phase for the sample at instant t2;
Comparing the values obtained in step b) and d) at instants t1 and t2 respectively;
Deducing therefrom whether the inflammatory reaction in response to a lesion or infection of the organism treatment changes favorably; and
Optionally, repeating steps a) to f)
Claim 7 is directed to a method for categorizing a subject suffering from an inflammatory reaction in response to a lesion or infection of the organism in a category C-1 at a degree of severity, from a subject suffering from the same in a category C-2 at another degree of severity, comprising:
Adding, in a biological sample of the subject, a composition as outlined above;
Measuring the amount of labeled ethanol released in the gas phase;
Comparing the values obtained in step b) with a corresponding standard control value; and
Deducing therefrom whether the subject is in the category C-1 or C-2
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 2, 3 and 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claims are directed to “use” claims of a composition and kit, but do not claim a process, machine, manufacture or composition of matter.
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.
Claims 1-10 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 is directed to a composition with an intended use of as a diagnostic and/or prognostic agent. However, the claim does not state what is being diagnosed or for what is a prognosis being given. Without this information, the metes and bounds of the intended use are not clear.
Regarding claims 1-10, the use of parentheses renders the claim indefinite because it is unclear whether the limitation(s) are part of the claimed invention.
Claims 2, 3 and 10 are directed to “use” of a composition and kit, but there are not recited steps for the intended uses. The metes and bounds of the claims cannot be determined.
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.
Claims 1 and 4-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a composition or kit comprising a composition comprising both ethyl-β-D-glucuronide and ethyl-β-D-galactopyranoside, wherein each have a non-radioactive isotope, does not reasonably provide enablement for the intended uses of the kit, i.e., diagnosis of an inflammatory reaction in response to a lesion or infection of the organism. Paragraph [0075] of the published application US-2024/0361317-A1 provides a non-limiting definition: “‘pathological conditions involving an inflammatory reaction in response to a lesion or infection of the organism’ denotes in particular cancers, pulmonary ARDS and fibrosis, or Parkinson’s disease”. The specification is also not enabling for the methods of claims 4-8, encompassing diagnosis, tracking and categorizing subjects for an inflammatory reaction in response to a lesion or infection of the organism.
The breadth of claim 1 encompasses the diagnosis and prognosis of anything. The breadth of claims 4-9 encompasses methods that diagnose, track efficacy of a curative or preventative treatment for, track the course of, and categorize a subject based on severity of an inflammatory reaction in response to a lesion or infection of the organism. As set forth above, such reactions and infections include but are not limited to cancers, pulmonary ARDS and fibrosis, and Parkinson’s disease.
The nature of the invention is induced volatolomics, wherein samples from patients are exposed to ethyl-β-D-glucuronide and ethyl-β-D-galactopyranoside, wherein each have a non-radioactive isotope, and measuring labeled ethanol to diagnose, track efficacy of a curative or preventative treatment for, track the course of, and categorize a subject based on severity of an inflammatory reaction in response to a lesion or infection of the organism.
The specification has provided a combination of D5-ethyl-β-D-glucuronide and D2-ethyl-β-D-galactopyranoside. Example 3 describes an experiment wherein four VOC-based probes (four different isotopes) are used to detect labeled ethanol in plasma from four patients having breast cancer and three patients having lung cancer, and compared with labeled ethanol from healthy plasma samples. Applicant found that three probes (including D5-ethyl-β-D-glucuronide) were able to distinguish between plasma from cancer patients (breast and lung) (see paragraphs [0332]-[0334] of the published application US-2024/0361317-A1). The other probe, D2-ethyl-β-D-galactopyranoside was not able to make a distinction between plasma from cancer patients and plasma from healthy subjects, but was activated in an in vivo method where mice with nasopharyngeal tumors were injected with D2-ethyl-β-D-galactopyranoside. Applicant concludes that D2-ethyl-β-D-galactopyranoside is able to discern tumors by location (see paragraphs [0335] and [0344] of the published application US-2024/0361317-A1)).
The specification has also provided a study of the enzymatic activities on cancer biopsies in Example 5. Four probes were used in a cocktail, including D5-ethyl-β-D-glucuronide and D2-ethyl-β-D-galactopyranoside. Cancerous tissues (whole or cut) were exposed to the probes and labeled ethanol was detected in the environment of mammary tumors (see paragraphs [0357] and [0362] of the published application US-2024/0361317-A1).
Also provided in the specification is Example 6, an ex vivo study to determine whether the probes are relevant in SARS-CoV-2 infection. D5-ethyl-β-D-glucuronide was shown to distinguish between three sets of patients with different age ranges and different symptoms based on severity of disease, while D2-ethyl-β-D-galactopyranoside does not (see paragraphs [0371]-[0372] and [0376] of the published application US-2024/0361317-A1).
Djago et al. (Nature Reviews, March 2021, 5(3):183-196, cited in the IDS filed 12/22/2023, “Djago”) discloses the use of in vivo volatolomics that makes use of D5-ethyl-β-D-glucuronide to distinguish between healthy mice and tumor-bearing mice, allowing the monitoring of tumors during chemotherapy (see page 187). Djago also discloses the use of D5-ethyl-β-D-glucuronide to detect pathogens, such as bacteria (see Table 1).
As seen in the examples in the specification, the use of the claimed probes to function as diagnostics, prognostics, trackers of an inflammatory reaction in response to a lesion or infection of the organism, categorizing severity of disease, etc., is still in its discovery phase given all of the factors that play into determining whether detectable labeled ethanol is indicative of, for example, cancer, not to mention some of the other diseases such as Parkinson’s disease and ARDS. The type of cancer, the stage of cancer, the probe and the amount of probe are not disclosed or understood at a level that one would be able to use the probes as claimed, or practice the methods as claimed with any degree of certainty. Applicant has only experimented with a few types of cancer and a viral pathogen, yet no standards have been established such that one would be able to make the comparisons referenced in the claims and arrive at the conclusions recited in the claims. The use of the probes in even one type of cancer or one viral infection appears finicky and has to be experimentally determined.
Djago opines that induced volatolomics “is still in its infancy”, noting that the selection of an enzyme target is dependent on the molecular pathophysiological mechanisms for each type of organ, tissue and cell (see pages 193-194, “Conclusion”). The work of comprehending the complexities of the molecular pathophysiological mechanisms for each type of organ, tissue and cell, and the selection of a probe, as well as factors that impact VOCs such as interindividual variability, individual daily variation, the impact of diet, healthy, medication, exercise, etc., all speak to a low level of predictability that the combination of ethyl-β-D-glucuronide and ethyl-β-D-galactopyranoside, wherein each have a non-radioactive isotope, would able to yield a diagnosis or prognosis for an inflammatory reaction in response to a lesion or infection of the organism.
Therefore, in view of breadth of the claims, the nature of the invention, the limited guidance in the specification, the limited working examples, the state of the art and low level of predictability, it would require undue experimentation to make or use the claimed invention.
This rejection may be overcome by the following:
Amend claims 1 and 9 to remove intended uses
Amend the method claims, for example, to methods of detecting labeled ethanol released in a gas phase from a subject having an inflammatory reaction in response to a lesion or infection of the organism, or equivalent language that does not recite limitations about comparisons with standard control values, deducing diagnosis, deducing efficacy of treatment, tracking efficacy of a treatment, deducing whether pathological condition changes are favorable, tracking the course of a condition, and deducing and categorizing a condition
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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