Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
This action is in response to the papers filed October 16, 2025.
Amendments
Applicant's response and amendment, filed October 16, 2025, to the prior Office Action is acknowledged. Applicant has withdrawn Claims 15-17.
Claims 1-17 are pending.
Election/Restrictions
Applicant has elected the invention of Group I, Claims 1-14, drawn to a method of treatment for a disease or disorder characterized by a gene regulatory network, classified in C12Q1/6886.
Claims 1-17 are pending.
Claims 15-17 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-14 are under consideration.
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 63/138,240 filed on January 15, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
Applicant has filed Information Disclosure Statements on July 19, 2023 that have been considered.
The information disclosure statements filed July 19, 2023 fail to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
Bibliographic information provided must be at least enough to identify the publication. author, title and date. For books, minimal information includes the author, title, and date. For periodicals, at least the title of the periodical, the volume number, date, and pages should be given.
NPL citations have been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
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.
Claim Objections
1. Claims 3 and 11 are objected to because of the following informalities: the comma punctuations, e.g. “B cell differentiation,”, should be external to the quotation marks.
Appropriate correction is required.
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.
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.
2. Claims 3 and 11 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.
The claims recite the limitations “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and “Fanconi Anemia and Checkpoint Recovery”, whereby the use of quotation marks denotes some sort of definition, and thus each is a relative term which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term(s) is/are indefinite because the specification does not clearly redefine the term(s).
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A”, but not “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation”, but not “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “Human Gonadal Sex Determination”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Human Gonadal Sex Determination”.
The claims denote, for example, a first gene regulatory network that falls within “B cell differentiation”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “B cell differentiation”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia ”, but not “Checkpoint Recovery”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Checkpoint Recovery”, but not “Fanconi Anemia”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The recitation implies a genus of unrecited and undisclosed gene regulatory networks by which each gene regulatory network, and the undisclosed identities of the genes within each of the GRNs, respectively, are recited at a high level of generality, thereby rendering the claim indefinite.
See further discussion below in the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
3. Claims 3 and 11 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
There is a lack of adequate written description regarding the nexus of the enormously vast genus of structurally and functionally unrecited and undisclosed genes [structures], and their corresponding gene regulatory network (GRNs) [function(s)].
The claims fail to recite, and the specification fails to disclose, the identities of the genes for each of the gene regulatory networks recited at a high level of generality.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims recite the limitations “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and “Fanconi Anemia and Checkpoint Recovery”, whereby the use of quotation marks denotes some sort of definition. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A”, but not “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation”, but not “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “Human Gonadal Sex Determination”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Human Gonadal Sex Determination”.
The claims denote, for example, a first gene regulatory network that falls within “B cell differentiation”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “B cell differentiation”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia”, but not “Checkpoint Recovery”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Checkpoint Recovery”, but not “Fanconi Anemia”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
4. Claim 9 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.
The claim recites the limitation “triggers undesirable side effects”, which is a relative term which renders the claim indefinite. The limitation “undesirable side effects” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. That which does/does not constitute an “undesirable side effect(s)” is considered an arbitrary and subjective determination.
The claim also recites the limitations “without triggering side effects” and “reduces side effects”, which are relative terms which renders the claim indefinite. The limitations “without triggering side effects” and “reduces side effects” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. That which does/does not constitute a “side effect(s)” which is to be reduced or prohibited is/are considered an arbitrary and subjective determination.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
5. Claims 1-14 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.
Claims 1 and 7 recite a method of treating a disease or disorder in a subject, the method comprising the steps of:
i) administering to the subject a composition comprising a therapeutic agent and an inert agent, thereby achieving a corresponding therapeutic response; and
ii) repeating step (i) one or more times until the inert agent triggers a GRN response and a corresponding therapeutic response without the therapeutic agent, thereby treating the disease or disorder by administering the inert agent.
There is insufficient antecedent basis for the limitation “until the inert agent triggers a GRN response and a corresponding therapeutic response without the therapeutic agent” in the claim because, by definition, step (i) requires the administration of both the therapeutic agent and the inert agent. Thus, the negative limitations “without the therapeutic agent” and “treating the disease or disorder by administering the inert agent” is/are not achieved by “repeating step (i)”. The claims are incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
6. Claims 1-14 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.
Claims 1 and 7 recite a method of treating a disease or disorder characterized by a gene regulatory network (GRN) in a subject, the method comprising the steps of:
i) administering to the subject a composition comprising a therapeutic agent (Claim 7, “standard dose”) and an inert agent, thereby achieving a corresponding therapeutic response; and
ii) repeating step (i) one or more times until the inert agent triggers a GRN response and a corresponding therapeutic response without the therapeutic agent, thereby treating the disease or disorder by administering the inert agent.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
A “therapeutic agent” relative to what organism? Relative to what disease/disorder condition? Relative to what phenotypic response?
A “standard dose” relative to what organism? Relative to what disease/disorder condition? Relative to what phenotypic response?
An “inert agent” relative to what organism? Relative to what disease/disorder condition? Relative to what phenotypic response?
The limitations “therapeutic agent”, “standard dose”, and “inert agent” is/are structures described using functional language, whereby the functional properties are dependent upon many different variable parameters, including, but not limited to:
the type of human or non-human animal subject to be treated [parameter 1];
the structure(s) of the therapeutic agent [parameter 2];
the administration route [parameter 3];
the dosage administered [parameter 4];
the disease/disorder/condition to be treated [parameter 5];
the gene regulatory network(s) to be triggered/not triggered [parameter 6]; and
the phenotypic response to be achieved [parameter 7].
The claim(s) also denote(s) that there is an amount of the pharmaceutical composition comprising the therapeutic agent that and/or inert agent that, upon administration to the subject, is not, in fact, “therapeutic” (syn. sub-therapeutic), “a standard dose”, or “inert”.
Parameter 1
The claims are broad for reasonably encompassing an enormous genus of prokaryotic and eukaryotic subjects (e.g. [0069], “These include GRNs at different strata of evolution (prokaryotes and eukaryotes)”, and thus encompasses essentially all extant lifeforms on the planet.
The claims are broad for encompassing about 0.8 to 1.6 million species of prokaryotes (Louca et al, A census-based estimate of Earth’s bacterial and archaeal diversity, PLoS Biology 17(2): e3000106, 30 pages, doi.org/10.1371/journal.pbio.3000106, 2019).
The claims are broad for encompassing about 8.7 million species of eukaryotic organisms, including about 250,000 species of eukaryotic protists, about 100,000 species of fungi, about 250,000 species of plants, and about 1,000,000 species of animals (The Five Kingdoms of Life; waynesword.palomar.edu/trfeb98.htm, last visited April 8, 2021).
Mongabay (How many plant species are there in the world? Scientists now have an answer, news.mongabay.com/2016/05/many-plants-world-scientists-may-now-answer/; May 12, 2016) is considered relevant prior art for having taught that there is an estimated 391,000 different vascular plant species currently known to science, according to a report by the Royal Botanic Gardens, Kew, in the United Kingdom.
The claims are broad for encompassing about 1,000,000 species of animals (Kingdoms of Life, waynesword.palomar.edu/trfeb98.htm, last visited April 8, 2021), wherein the mammalian sub-genus reasonably encompasses some 6,400 species (including humans), distributed in about 1,200 genera, about 152 families and about 29 orders (Mammal, en.wikipedia.org/wiki/Mammal, last visited August 31, 2022).
Parameter 2
The claims are broad for reasonably encompassing an enormous genus of structurally and functionally unrecited and undisclosed therapeutic and/or inert agents identified solely using functional language of “therapeutic agent”, whereby said agent may be a radiological agent, e.g. X-rays, a thermal agent, sound waves, a chemical, metal, fat, carbohydrate, nucleic acid, peptide, or a polypeptide agent.
The specification discloses the therapeutic agent may be a potent drug (e.g. [0005]), whereby “potent” is also relative terminology, arbitrary and subjective functional language.
The specification discloses the inert agent may be a harmless drug (e.g. [0005]), whereby “harmless” is also relative terminology, arbitrary and subjective functional language.
The specification fails to disclose a working example of administering a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder.
The specification fails to disclose a working example of administering a “standard dose” of a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claims 1 and 7).
The specification fails to disclose a working example of administering an inert agent [structure] to a subject, in the absence of a therapeutic agent, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claim 7).
The specification fails to disclose a working example of administering a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claims 1 and 7).
The specification fails to disclose a working example of repeated administration of an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves the negative limitation of ceasing to trigger a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claims 2 and 8).
The specification fails to disclose a working example of administering lowered dose(s) of a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property] without triggering side effects or reduces side effects [functional properties], thereby treating the disease/disorder (Claim 9).
The specification fails to disclose a working example of administering lowered dose(s) of a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves ceasing to trigger a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claim 10).
Parameter 3
The claimed methods are recited at a high level of generality for the route by which the therapeutic agent is to be administered to the subject, including, but not limited to, electroporation, biolistic delivery, direct cellular injection, systemically, regionally or locally, or by any route, for example, by injection, infusion, orally, alimentary, ingestion, inhalation, mucosal, respiration, intranasal, intubation, intrapulmonary, intrapulmonary instillation, buccal, sublingual, otopically, transdermally, dermal, intradermal, subcutaneously, parenterally, transmucosally, rectally, intracavity, intraglandular, intra-pleurally, intraperitoneally, intravenously, intrarterial, intravascular, intramuscularly, intracranially, intra-spinal, intrathecal, iontophoretic, intraocular, ophthalmic, optical, intraorgan, or intralymphatic (e.g. High et al (U.S. 2015/0111955, [0077]).
The specification fails to disclose a working example of administering a therapeutic agent to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet.
Parameter 4
The claimed methods are recited at a high level of generality for therapeutic agent dosage and inert agent dosage to be administered.
The claim(s) denotes that there is a first amount of the therapeutic agent that is not a “standard dose”, as opposed to a second amount that is a “standard dose”.
The claim(s) denotes that there is a first amount of the therapeutic agent [structure] that is not able to trigger a GRN response [functional property] and/or therapeutic response [functional property], as opposed to a second amount that is necessarily and predictably able to achieve triggering a GRN response [functional property] and/or therapeutic response [functional property],
See also discussion above per Parameter 2.
Parameter 5
The claimed methods are recited at a high level of generality for enormously vast genus of etiologically and pathologically distinct diseases and/or disorders to be treated.
Clark et al (Genes, Genomes, and DNA, in Molecular Biology (Third Edition), doi.org/10.1016/C2015-0-06229-3; Elsevier, 2019; excerpted portions only) is considered relevant prior art for having taught that bacterial genomes may comprise as few as 140 to as many as 9,000 different genes, protist genomes may comprise as many as 60,000 different genes, animal genomes may comprise as many as 25,000 different genes, and plant genomes may comprise as many as 95,000 different genes (e.g. Table 4.01, Genome Sizes).
The claims would appear to encompass essentially all disorders or conditions caused by mutation of essentially all genes.
Parameter 6
As discussed above, the claims would appear to encompass an enormously vast genus of structurally and functionally undisclosed gene regulatory networks comprising as few as 140 to as many as 95,000 different genes.
The claims would appear to encompass essentially all genes and their functional biological relationships, however directly or indirectly that might be.
Claims 3 and 11 recite the gene regulatory network limitations “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and “Fanconi Anemia and Checkpoint Recovery”, whereby the use of quotation marks denotes some sort of definition. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A”, but not “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation”, but not “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “Human Gonadal Sex Determination”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Human Gonadal Sex Determination”.
The claims denote, for example, a first gene regulatory network that falls within “B cell differentiation”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “B cell differentiation”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia ”, but not “Checkpoint Recovery”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Checkpoint Recovery”, but not “Fanconi Anemia”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims fail to recite, and the specification fails to disclose, the identities of the genes [structures] present in each of the “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and “Fanconi Anemia and Checkpoint Recovery” gene regulatory networks [function], thereby defining each of the GRNs, respectively.
The specification fails to disclose a working example of a first amount of a therapeutic agent, let alone one that is a “standard dose”, nor a non-standard dose, alone and/or in combination with an inert agent, or inert agent alone, thereby necessarily and predictably treating the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders in the enormously vast genus of subjects, whereby said therapeutic agent and/or inert agent triggers or does not trigger a “Aurora Kinase A in Neuroblastoma” gene regulatory network (GRN), but does not trigger a “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and/or “Fanconi Anemia and Checkpoint Recovery” gene regulatory network (GRN), for example.
The specification fails to disclose a working example of a first amount of a therapeutic agent, let alone one that is a “standard dose”, nor a non-standard dose, alone and/or in combination with an inert agent, or inert agent alone, thereby necessarily and predictably treating the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders in the enormously vast genus of subjects, whereby said therapeutic agent and/or inert agent triggers or does not trigger a “CD4+ T Cell Differentiation and Plasticity” gene regulatory network (GRN), but does not trigger a “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and/or “Fanconi Anemia and Checkpoint Recovery” gene regulatory network (GRN), for example.
Parameter 7
The claimed methods are recited at a high level of generality for the phenotypic response(s) to be achieved upon administering the standard dose of the therapeutic agent to the subject, which evokes the question: A therapeutically effective amount to do what?
The common phrase “an effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. In reFredericksen, 213 F.2d 547, 102 USPQ 35 (CCPA 1954). MPEP 2173.05(c)
It is understood that in order to meaningfully treat the subject, and thereby satisfy the requirements of 35 U.S.C. 101 (See MPEP 2107.01 III, Therapeutic or Pharmacological Utility), a therapeutically effective amount or dose of the therapeutic agent must be administered to the subject, thereby achieving some real-world, clinically meaningful effect, and thereby being of “immediate benefit to the public”.
It is apparent that the amount must be therapeutic. Even so, the various endpoints and extents that define effective treatment are more of a conditional or qualitative nature. As such, it is not evident what effect is necessarily achieved. Rather, the expected or desired effect that is to be achieved in the practice of the claimed invention to treat the subject is considered highly subjective and would tend to vary substantially.
The claims would appear to encompass some arbitrary and subjective response that may or may not be therapeutic, e.g. amelioration, by however small amount, of some unrecited and undisclosed symptom of the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders to be treated.
The recitation implies a genus of unrecited and undisclosed phenotypes by which the therapeutically effective dose and/or standard dose is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The specification fails to disclose a working example of a first amount of a therapeutic agent that is a “standard dose”, nor a non-standard dose, thereby necessarily and predictably treating the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders in the enormously vast genus of subjects.
The recitation implies a genus of unrecited and undisclosed phenotypes by which the therapeutically effective dose is to be determined and/or identified, whereby the therapeutically effective amount of the therapeutic agent dosage administered is a result-effective variable dependent upon many different parameters, thereby rendering the claim indefinite.
See further discussion below in the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claims.
Appropriate correction is required.
7. Claims 1-14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
Claims 1 and 7 recite a method of treating a disease or disorder in a subject, the method comprising the steps of:
i) administering to the subject a composition comprising a therapeutic agent (Claim 7, “standard dose”) and an inert agent, thereby achieving a corresponding therapeutic response; and
ii) repeating step (i) one or more times until the inert agent triggers a GRN response and a corresponding therapeutic response without the therapeutic agent, thereby treating the disease or disorder by administering the inert agent.
Claims 1 and 7 also recite the step of administering to the subject an inert agent, wherein the inert agent does not trigger a response in the gene regulatory network (GRN).
The therapeutic agent is recited at a high level of generality using only functional language.
The inert agent is recited at a high level of generality using only functional language.
There is a lack of adequate written description regarding the nexus of the enormously vast genus of structurally and functionally unrecited and undisclosed therapeutic agents [structures], and their corresponding dosages, that necessarily and predictably achieve a therapeutic response(s) [function(s)], alone and/or in combination with the enormously vast genus of structurally and functionally unrecited and undisclosed inert agents [structures], and their corresponding dosages, that necessarily and predictably achieves a triggering or non-triggering response(s) [function(s)] in the enormously vast genus of structurally unrecited and undisclosed gene regulatory networks (GRNs).
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
A “therapeutic agent” relative to what organism? Relative to what disease/disorder condition? Relative to what phenotypic response?
A “standard dose” relative to what organism? Relative to what disease/disorder condition? Relative to what phenotypic response?
An “inert agent” relative to what organism? Relative to what disease/disorder condition? Relative to what phenotypic response?
The limitations “therapeutic agent”, “standard dose”, and “inert agent” is/are structures described using functional language, whereby the functional properties are dependent upon many different variable parameters, including, but not limited to:
the type of human or non-human animal subject to be treated [parameter 1];
the structure(s) of the therapeutic agent [parameter 2];
the administration route [parameter 3];
the dosage administered [parameter 4];
the disease/disorder/condition to be treated [parameter 5];
the gene regulatory network(s) to be triggered/not triggered [parameter 6]; and
the phenotypic response to be achieved [parameter 7].
The claim(s) also denote(s) that there is an amount of the pharmaceutical composition comprising the therapeutic agent that and/or inert agent that, upon administration to the subject, is not, in fact, “therapeutic” (syn. sub-therapeutic), “a standard dose”, or “inert”.
Parameter 1
As discussed above, the claims are broad for reasonably encompassing an enormous genus of prokaryotic and eukaryotic subjects (e.g. [0069], “These include GRNs at different strata of evolution (prokaryotes and eukaryotes)”, and thus encompasses essentially all extant lifeforms on the planet, including about 1.6x10^6 species of prokaryotes and about 8.7 x10^6 species of eukaryotic organisms, such as protists, fungi, plants, and animals.
Parameter 2
The claims are broad for reasonably encompassing an enormous genus of structurally and functionally unrecited and undisclosed agents identified solely using functional language of “therapeutic agent”, whereby said agent may be a radiological agent, e.g. X-rays, a thermal agent, sound waves, a chemical, metal, fat, carbohydrate, nucleic acid, peptide, or a polypeptide agent.
The claims are broad for reasonably encompassing an enormous genus of structurally and functionally unrecited and undisclosed agents identified solely using functional language of “inert agent”, whereby said agent may be a radiological agent, e.g. X-rays, a thermal agent, sound waves, a chemical, metal, fat, carbohydrate, nucleic acid, peptide, or a polypeptide agent.
The specification discloses the therapeutic agent may be a potent drug (e.g. [0005]), whereby “potent” is also relative terminology, arbitrary and subjective functional language.
The specification discloses the inert agent may be a harmless drug (e.g. [0005]), whereby “harmless” is also relative terminology, arbitrary and subjective functional language.
The claims encompass an infinite genus of structurally and functionally undisclosed “agents”, be they “therapeutic” or “inert”.
The claims encompass an infinite genus of structurally and functionally undisclosed nucleic acid sequences being up to 500 nucleotides in length (4^500 = infinite; calculator.net/exponent-calculator.html; last visited January 20, 2026), be they “therapeutic” or “inert”.
The claims encompass an infinite genus of structurally and functionally undisclosed polypeptide sequences being up to 250 amino acids in length (20^250 = infinite; calculator.net/exponent-calculator.html; last visited January 20, 2026), be they “therapeutic” or “inert”.
The specification fails to disclose a working example of administering a therapeutic agent and/or inert agent to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet.
Those of ordinary skill in the art immediately recognize that Applicant simply does not possess infinity!
The specification fails to disclose a working example of administering a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder.
The specification fails to disclose a working example of administering a “standard dose” of a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claims 1 and 7).
The specification fails to disclose a working example of administering an inert agent [structure] to a subject, in the absence of a therapeutic agent, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claim 7).
The specification fails to disclose a working example of administering a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claims 1 and 7).
The specification fails to disclose a working example of repeated administration of an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves the negative limitation of ceasing to trigger a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claims 2 and 8).
The specification fails to disclose a working example of administering lowered dose(s) of a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves triggering a GRN response [functional property] and a therapeutic response [functional property] without triggering side effects or reduces side effects [functional properties], thereby treating the disease/disorder (Claim 9).
The specification fails to disclose a working example of administering lowered dose(s) of a therapeutic agent [structure] and an inert agent [structure] to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet, that necessarily and predictably achieves ceasing to trigger a GRN response [functional property] and a therapeutic response [functional property], thereby treating the disease/disorder (Claim 10).
Parameter 3
The claimed methods are recited at a high level of generality for the route by which the therapeutic agent is to be administered to the subject, including, but not limited to, electroporation, biolistic delivery, direct cellular injection, systemically, regionally or locally, or by any route, for example, by injection, infusion, orally, alimentary, ingestion, inhalation, mucosal, respiration, intranasal, intubation, intrapulmonary, intrapulmonary instillation, buccal, sublingual, otopically, transdermally, dermal, intradermal, subcutaneously, parenterally, transmucosally, rectally, intracavity, intraglandular, intra-pleurally, intraperitoneally, intravenously, intrarterial, intravascular, intramuscularly, intracranially, intra-spinal, intrathecal, iontophoretic, intraocular, ophthalmic, optical, intraorgan, or intralymphatic (e.g. High et al (U.S. 2015/0111955, [0077]).
The specification fails to disclose a working example of administering a therapeutic agent and/or inert agent to a subject, let alone the enormously vast genus of essentially all extant lifeforms on the planet.
Parameter 4
The claimed methods are recited at a high level of generality for therapeutic agent dosage and inert agent dosage to be administered.
The claim(s) denotes that there is a first amount of the therapeutic agent that is not a “standard dose”, as opposed to a second amount that is a “standard dose”.
The claim(s) denotes that there is a first amount of the therapeutic agent [structure] that is not able to trigger a GRN response [functional property] and/or therapeutic response [functional property], as opposed to a second amount that is necessarily and predictably able to achieve triggering a GRN response [functional property] and/or therapeutic response [functional property],
See also discussion above per Parameter 2.
Parameter 5
The claimed methods are recited at a high level of generality for enormously vast genus of etiologically and pathologically distinct diseases and/or disorders to be treated.
Clark et al (Genes, Genomes, and DNA, in Molecular Biology (Third Edition), doi.org/10.1016/C2015-0-06229-3; Elsevier, 2019; excerpted portions only) is considered relevant prior art for having taught that bacterial genomes may comprise as few as 140 to as many as 9,000 different genes, protist genomes may comprise as many as 60,000 different genes, animal genomes may comprise as many as 25,000 different genes, and plant genomes may comprise as many as 95,000 different genes (e.g. Table 4.01, Genome Sizes).
The claims would appear to encompass essentially all disorders or conditions caused by mutation of essentially all genes.
Parameter 6
As discussed above, the claims would appear to encompass an enormously vast genus of structurally and functionally undisclosed gene regulatory networks comprising as few as 140 to as many as 95,000 different genes.
The claims would appear to encompass essentially all genes and their functional biological relationships, however directly or indirectly that might be.
Claims 3 and 11 recite the gene regulatory network limitations “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and “Fanconi Anemia and Checkpoint Recovery”, whereby the use of quotation marks denotes some sort of definition. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “Aurora Kinase A”, but not “Aurora Kinase A in Neuroblastoma”, as opposed to a second gene regulatory network that falls within “Aurora Kinase A in Neuroblastoma”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “CD4+ T Cell Differentiation”, but not “CD4+ T Cell Differentiation and Plasticity”, as opposed to a second gene regulatory network that falls within “CD4+ T Cell Differentiation and Plasticity”.
The claims denote, for example, a first gene regulatory network that falls within “Human Gonadal Sex Determination”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Human Gonadal Sex Determination”.
The claims denote, for example, a first gene regulatory network that falls within “B cell differentiation”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “B cell differentiation”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”, as opposed to a second gene regulatory network that is outside of, does not touch upon, overlaps with, and/or falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Fanconi Anemia ”, but not “Checkpoint Recovery”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims denote, for example, a first gene regulatory network that falls within “Checkpoint Recovery”, but not “Fanconi Anemia”, as opposed to a second gene regulatory network that falls within “Fanconi Anemia and Checkpoint Recovery”.
The claims fail to recite, and the specification fails to disclose, the identities of the genes [structures] present in each of the “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and “Fanconi Anemia and Checkpoint Recovery” gene regulatory networks [function], thereby defining each of the GRNs, respectively.
The specification fails to disclose a working example of a first amount of a therapeutic agent, let alone one that is a “standard dose”, nor a non-standard dose, alone and/or in combination with an inert agent, or inert agent alone, thereby necessarily and predictably treating the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders in the enormously vast genus of subjects, whereby said therapeutic agent and/or inert agent triggers or does not trigger a “Aurora Kinase A in Neuroblastoma” gene regulatory network (GRN), but does not trigger a “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and/or “Fanconi Anemia and Checkpoint Recovery” gene regulatory network (GRN), for example.
The specification fails to disclose a working example of a first amount of a therapeutic agent, let alone one that is a “standard dose”, nor a non-standard dose, alone and/or in combination with an inert agent, or inert agent alone, thereby necessarily and predictably treating the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders in the enormously vast genus of subjects, whereby said therapeutic agent and/or inert agent triggers or does not trigger a “CD4+ T Cell Differentiation and Plasticity” gene regulatory network (GRN), but does not trigger a “Aurora Kinase A in Neuroblastoma”, “CD4+ T Cell Differentiation and Plasticity”, “Human Gonadal Sex Determination”, “B cell differentiation”, and/or “Fanconi Anemia and Checkpoint Recovery” gene regulatory network (GRN), for example.
Parameter 7
The claimed methods are recited at a high level of generality for the phenotypic response(s) to be achieved upon administering the standard dose of the therapeutic agent to the subject, which evokes the question: A therapeutically effective amount to do what?
The common phrase “an effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. In reFredericksen, 213 F.2d 547, 102 USPQ 35 (CCPA 1954). MPEP 2173.05(c)
It is understood that in order to meaningfully treat the subject, and thereby satisfy the requirements of 35 U.S.C. 101 (See MPEP 2107.01 III, Therapeutic or Pharmacological Utility), a therapeutically effective amount or dose of the therapeutic agent must be administered to the subject, thereby achieving some real-world, clinically meaningful effect, and thereby being of “immediate benefit to the public”.
It is apparent that the amount must be therapeutic. Even so, the various endpoints and extents that define effective treatment are more of a conditional or qualitative nature. As such, it is not evident what effect is necessarily achieved. Rather, the expected or desired effect that is to be achieved in the practice of the claimed invention to treat the subject is considered highly subjective and would tend to vary substantially.
The claims would appear to encompass some arbitrary and subjective response that may or may not be therapeutic, e.g. amelioration, by however small amount, of some unrecited and undisclosed symptom of the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders to be treated.
The recitation implies a genus of unrecited and undisclosed phenotypes by which the therapeutically effective dose and/or standard dose is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The specification fails to disclose a working example of a first amount of a therapeutic agent that is a “standard dose”, nor a non-standard dose, thereby necessarily and predictably treating the enormously vast genus of etiologically and pathologically distinct diseases and/or disorders in the enormously vast genus of subjects.
In Amgen, Inc., v. Sanofi (872 F.3d 1367 (2017)
At 1375, [T]he use of post-priority-date evidence to show that a patent does not disclose a representative number of species of a claimed genus is proper.
At 1377, [W]e questioned the propriety of the "newly characterized antigen" test and concluded that instead of "analogizing the antibody-antigen relationship to a `key in a lock,'" it was more apt to analogize it to a lock and "a ring with a million keys on it." Id. at 1352.
An adequate written description must contain enough information about the actual makeup of the claimed products — "a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials," which may be present in "functional" terminology "when the art has established a correlation between structure and function." Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5-
16) (Appellants' expert Dr. Eck testifying that knowing "that an antibody binds to a particular amino acid on PCSK9 ... does not tell you anything at all about the structure of the antibody"); J.A. 1314 (836:9-11) (Appellees' expert Dr. Petsko being informed of Dr. Eck's testimony and responding that "[m]y opinion is that [he's] right"); Centocor, 636 F.3d at 1352 (analogizing the antibody-antigen relationship as searching for a key "on a ring with a million keys on it") (internal citations and quotation marks omitted).
In the instant case, knowing that the initial agent is to have some therapeutic functional property does not tell you anything at all about the structure of the enormously vast genus of radiological or thermal therapeutic agents, the essentially infinite genus of chemical therapeutic agent compounds, the essentially infinite genus of nucleic acid therapeutic agent compounds, and/or the essentially infinite genus of amino acid therapeutic agent compounds.
Similarly, knowing that the initial agent is to be inert in some manner [functional property] does not tell you anything at all about the structure of the enormously vast genus of radiological or thermal inert agents, the essentially infinite genus of chemical inert agent compounds, the essentially infinite genus of nucleic acid inert agent compounds, and/or the essentially infinite genus of amino acid inert agent compounds.
In Amgen, Inc., v. Sanofi (U.S. Supreme Court, No. 21-757 (2023))
“Amgen seeks to monopolize an entire class of things defined by their function”.
“The record reflects that this class of antibodies does not include just the 26 that Amgen has described by their amino acid sequence, but a “vast” number of additional antibodies that it has not.”
“It freely admits that it seeks to claim for itself an entire universe of antibodies.”
In the instant case, the record reflects that the claims reasonably encompass:
i) an enormously vast genus of radiological or thermal therapeutic agents, an essentially infinite genus of chemical therapeutic agent compounds, an essentially infinite genus of nucleic acid therapeutic agent compounds, and/or an essentially infinite genus of amino acid therapeutic agent compounds;
ii) an enormously vast genus of radiological or thermal inert agents, an essentially infinite genus of chemical inert agent compounds, an essentially infinite genus of nucleic acid inert agent compounds, and/or an essentially infinite genus of amino acid inert agent compounds;
iii) an enormously vast genus of disorders or conditions caused by mutation of essentially all genes to be treated;
iv) an enormously vast genus of therapeutic responses to be achieved;
v) an enormously vast genus of structurally and functionally undisclosed gene regulatory networks comprising as few as 140 to as many as 95,000 different genes and their functional biological relationships, however directly or indirectly that might be, that are and/or are not to be triggered by the therapeutic agent and/or inert agent; and
vi) the enormously genus of prokaryotic and eukaryotic subjects, essentially all extant lifeforms on the planet, including about 1.6x10^6 species of prokaryotes and about 8.7 x10^6 species of eukaryotic organisms, such as protists, fungi, plants, and animals to be treated.
“They leave a scientist forced to engage in painstaking experimentation to see what works. 159 U.S., at 475.
This is not enablement. More nearly, it is “a hunting license”. Brenner v. Manson, 383 U.S. 519, 536 (1966).
“Amgen has failed to enable all that it has claimed, even allowing for a reasonable degree of experimentation”.
While the “roadmap” would produce functional combinations, it would not enable others to make and use the functional combinations; it would instead leave them to “random trial-and-error discovery”.
“Amgen offers persons skilled in the art little more than advice to engage in “trial and error”.
“The more a party claims for itself the more it must enable.”
“Section 112 of the Patent Act reflects Congress’s judg-ment that if an inventor claims a lot, but enables only a lit-tle, the public does not receive its benefit of the bargain. For more than 150 years, this Court has enforced the stat-utory enablement requirement according to its terms. If the Court had not done so in Incandescent Lamp, it might have been writing decisions like Holland Furniture in the dark. Today’s case may involve a new technology, but the legal principle is the same.
Instant specification fails to disclose a working example of the broadly claimed method.
Essentially, Applicant is requiring the ordinary artisans to discover for themselves that which Applicant fails to disclose.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
8. Claims 1-14 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
In Amgen, Inc., v. Sanofi (872 F.3d 1367 (2017)
At 1375, [T]he use of post-priority-date evidence to show that a patent does not disclose a representative number of species of a claimed genus is proper.
At 1377, [W]e questioned the propriety of the "newly characterized antigen" test and concluded that instead of "analogizing the antibody-antigen relationship to a `key in a lock,'" it was more apt to analogize it to a lock and "a ring with a million keys on it." Id. at 1352.
An adequate written description must contain enough information about the actual makeup of the claimed products — "a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials," which may be present in "functional" terminology "when the art has established a correlation between structure and function." Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5-
16) (Appellants' expert Dr. Eck testifying that knowing "that an antibody binds to a particular amino acid on PCSK9 ... does not tell you anything at all about the structure of the antibody"); J.A. 1314 (836:9-11) (Appellees' expert Dr. Petsko being informed of Dr. Eck's testimony and responding that "[m]y opinion is that [he's] right"); Centocor, 636 F.3d at 1352 (analogizing the antibody-antigen relationship as searching for a key "on a ring with a million keys on it") (internal citations and quotation marks omitted).
In the instant case, knowing that the initial agent is to have some therapeutic functional property does not tell you anything at all about the structure of the enormously vast genus of radiological or thermal therapeutic agents, the essentially infinite genus of chemical therapeutic agent compounds, the essentially infinite genus of nucleic acid therapeutic agent compounds, and/or the essentially infinite genus of amino acid therapeutic agent compounds.
Similarly, knowing that the initial agent is to be inert in some manner [functional property] does not tell you anything at all about the structure of the enormously vast genus of radiological or thermal inert agents, the essentially infinite genus of chemical inert agent compounds, the essentially infinite genus of nucleic acid inert agent compounds, and/or the essentially infinite genus of amino acid inert agent compounds.
In Amgen, Inc., v. Sanofi (U.S. Supreme Court, No. 21-757 (2023))
“Amgen seeks to monopolize an entire class of things defined by their function”.
“The record reflects that this class of antibodies does not include just the 26 that Amgen has described by their amino acid sequence, but a “vast” number of additional antibodies that it has not.”
“It freely admits that it seeks to claim for itself an entire universe of antibodies.”
In the instant case, the record reflects that the claims reasonably encompass:
i) an enormously vast genus of radiological or thermal therapeutic agents, an essentially infinite genus of chemical therapeutic agent compounds, an essentially infinite genus of nucleic acid therapeutic agent compounds, and/or an essentially infinite genus of amino acid therapeutic agent compounds;
ii) an enormously vast genus of radiological or thermal inert agents, an essentially infinite genus of chemical inert agent compounds, an essentially infinite genus of nucleic acid inert agent compounds, and/or an essentially infinite genus of amino acid inert agent compounds;
iii) an enormously vast genus of disorders or conditions caused by mutation of essentially all genes to be treated;
iv) an enormously vast genus of therapeutic responses to be achieved;
v) an enormously vast genus of structurally and functionally undisclosed gene regulatory networks comprising as few as 140 to as many as 95,000 different genes and their functional biological relationships, however directly or indirectly that might be, that are and/or are not to be triggered by the therapeutic agent and/or inert agent; and
vi) the enormously genus of prokaryotic and eukaryotic subjects, essentially all extant lifeforms on the planet, including about 1.6x10^6 species of prokaryotes and about 8.7 x10^6 species of eukaryotic organisms, such as protists, fungi, plants, and animals to be treated.
“They leave a scientist forced to engage in painstaking experimentation to see what works. 159 U.S., at 475.
This is not enablement. More nearly, it is “a hunting license”. Brenner v. Manson, 383 U.S. 519, 536 (1966).
“Amgen has failed to enable all that it has claimed, even allowing for a reasonable degree of experimentation”.
While the “roadmap” would produce functional combinations, it would not enable others to make and use the functional combinations; it would instead leave them to “random trial-and-error discovery”.
“Amgen offers persons skilled in the art little more than advice to engage in “trial and error”.
“The more a party claims for itself the more it must enable.”
“Section 112 of the Patent Act reflects Congress’s judg-ment that if an inventor claims a lot, but enables only a lit-tle, the public does not receive its benefit of the bargain. For more than 150 years, this Court has enforced the stat-utory enablement requirement according to its terms. If the Court had not done so in Incandescent Lamp, it might have been writing decisions like Holland Furniture in the dark. Today’s case may involve a new technology, but the legal principle is the same.
Instant specification fails to disclose a working example of the broadly claimed method.
Essentially, Applicant is requiring the ordinary artisans to discover for themselves that which Applicant fails to disclose.
The Quantity of Any Necessary Experimentation to Make or Use the Invention
It is generally recognized in the art that biological compounds often react unpredictably under different circumstances (Nationwide Chem. Corp. v. Wright, 458 F. supp. 828, 839, 192 USPQ95, 105(M.D. Fla. 1976); Affd 584 F.2d 714, 200 USPQ257 (5th Cir. 1978); In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970)). The relative skill of the artisan and the unpredictability of the pharmaceutical art are very high. Where the physiological activity of a chemical or biological compound is considered to be an unpredictable art (Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved" (See In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970))), the skilled artisan would have not known how to administer an infinite genus of structurally and functionally undisclosed therapeutic agents and/or an infinite genus of structurally and functionally undisclosed inert agents to the enormously vast genus of subjects, essentially all extant lifeforms on the planet, so as to necessarily and predictably trigger and/or not trigger the enormously vast genus of structurally and functionally undisclosed gene regulatory networks, thereby necessarily and predictably achieving a real-world, clinically meaningful therapeutic result in the essentially all extant lifeforms on the planet, including about 1.6x10^6 species of prokaryotes and about 8.7 x10^6 species of eukaryotic organisms, such as protists, fungi, plants, and animals to be treated.
Instant specification fails to disclose how to extrapolate the one or more at least seven (7) method parameters, as applied to an in vitro subject, e.g. a bacterium, to the one or more at least seven (7) method parameters, as applied to an in vivo subject, e.g. Arabidopsis plant.
Instant specification fails to disclose how to extrapolate the one or more at least seven (7) method parameters, as applied to an in vitro subject, e.g. a protist, to the one or more at least seven (7) method parameters, as applied to an in vivo subject, e.g. Aedes mosquito.
Instant specification fails to disclose how to extrapolate the one or more at least seven (7) method parameters, as applied to an in vitro subject, e.g. fungal cells, to the one or more at least seven (7) method parameters, as applied to an in vivo subject, e.g. horse.
Instant specification fails to disclose how to extrapolate the one or more at least seven (7) method parameters, as applied to a first in vivo subject, e.g. a guinea pig, to the one or more at least seven (7) method parameters, as applied to a second in vivo subject, e.g. a human.
The instant portion of the invention, as claimed, falls under the "germ of an idea" concept defined by the CAFC. The court has stated that "patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be workable". The court continues to say that "tossing out the mere germ of an idea does not constitute an enabling disclosure" and that "the specification, not knowledge in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". (See Genentech Inc v. Novo Nordisk A/S 42 USPQ2d 1001, at 1005).
The courts have stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in patent application. 27 USPQ2d 1662 Exparte Maizel. In the instant case, in view of the lack of guidance, working examples, breadth of the claims, the level of skill in the art and state of the art at the time of the claimed invention was made, it would have required undue experimentation to make and/or use the invention as claimed.
If little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004) ("Nascent technology, however, must be enabled with a 'specific and useful teaching.' The law requires an enabling disclosure for nascent technology because a person of ordinary skill in the art has little or no knowledge independent from the patentee's instruction. Thus, the public's end of the bargain struck by the patent system is a full enabling disclosure of the claimed technology." (citations omitted)).
As In re Gardner, Roe and Willey, 427 F.2d 786,789 (C.C.P.A. 1970), the skilled artisan might eventually find out how to use the invention after “a great deal of work”. In the case of In re Gardner, Roe and Willey, the invention was a compound which the inventor claimed to have antidepressant activity, but was not enabled because the inventor failed to disclose how to use the invention based on insufficient disclosure of effective drug dosage. The court held that “the law requires that the disclosure in the application shall inform them how to use, not how to find out how to use for themselves”.
Perrin (Make mouse studies work, Nature (507): 423-425, 2014) taught that the series of clinical trials for a potential therapy can cost hundreds of millions of dollars. The human costs are even greater (pg 423, col. 1). For example, while 12 clinical trials were tested for the treatment of ALS, all but one failed in the clinic (pg 423, col. 2). Experiments necessary in preclinical animal models to characterize new drugs or therapeutic compounds are expensive, time-consuming, and will not, in themselves, lead to new treatments. But without this upfront investment, financial resources for clinical trials are being wasted and [human] lives are being lost (pg 424, col. 1). Animal models are highly variable, and require a large number of animals per test group. Before assessing a drug’s efficacy, researchers should investigate what dose animals can tolerate, whether the drug reaches the relevant tissue at the required dose and how quickly the drug is metabolized or degraded by the body. We estimate that it takes about $30,000 and 6–9 months to characterize the toxicity of a molecule and assess whether enough reaches the relevant tissue and has a sufficient half-life at the target to be potentially effective. If those results are promising, then experiments to test whether a drug can extend an animal’s survival are warranted — this will cost about $100,000 per dose and take around 12 months. At least three doses of the molecule should be tested; this will help to establish that any drug responses are real and suggest what a reasonable dosing level might be. Thus, even assuming the model has been adequately characterized, an investment of $330,000 is necessary just to determine whether a single drug has reasonable potential to treat disease in humans. It could take thousands of patients, several years and hundreds of millions of dollars to move a drug through the clinical development process. The investment required in time and funds is far beyond what any one lab should be expected to do. (pg 425, col.s 2-3). The human costs are even greater: patients with progressive terminal illnesses may have just one shot at an unproven but promising treatment. Clinical trials typically require patients to commit to year or more of treatment, during which they are precluded from pursuing other experimental options (pg 423, col.2 1-3).
Greenberg (Gene Therapy for heart failure, Trends in Cardiovascular Medicine 27: 216-222, 2017) is considered relevant prior art for taught that despite success in experimental animal models, translating gene transfer strategies from the laboratory to the clinic remains at an early stage (Abstract). The success of gene therapy depends on a variety of factors that will ultimately determine the level of transgene expression within the targeted cells. These factors include the vector used for delivery, the method and conditions of delivery of the vector to the [target tissue], the dose that is given and interactions between the host and the vector that alter the efficiency of transfection of [target] cells (e.g. pg 217, col. 1). Failure of therapeutic results may arise because the vector DNA levels were at the lower end of the threshold for dose-response curves in pharmacology studies, and/or only a small proportion of target cells were expressing the therapeutic transgene (e.g. pg 220, col. 1). Although the use of AAVs for gene therapy is appealing, additional information about the best strain of AAVs to use in human patients is needed. Experience indicates that there is a need to carefully consider the dose of the gene therapy vector; however, this has proved to be difficult in early phase developmental studies due to the complexity and cost of such studies (e.g. pg 221, col. 1).
Maguire et al (Viral vectors for gene delivery to the inner ear, Hearing Research 394: e107927, 13 pages, doi.org/10.1016/j.heares.2020.107927, 2020) is considered relevant post-filing art for taught that despite the progress with AAV vectors in the inner ear, little is known regarding the mechanism of transduction of specific cells by AAV within the cochlea (e.g. pg 2, col. 2). There are limitations to what experiments in mice can tell us about the true translation potential of a new therapeutic (e.g. pg 8, col. 2), e.g. species-related physiological differences between mice and humans (e.g. pg 9, col. 1). The AAV dosage is a significant factor in achieving transduction of the target cell, as insufficient dosage may achieve no transduction of the target cells (e.g. pg 9, col. 2).
Tobias (Mouse Study Used in Research, Multiple Sclerosis News Today, multiplesclerosisnewstoday.com/news-posts/2023/09/08/lets-not-get-overexcited-about-any-mice-study-used-research/; September 8, 2023) is considered relevant art for having taught that, “Mice exaggerate and monkeys lie, some researchers jokingly say. (Or is it the other way around?)” The odds of an experimental treatment making it from mouse or monkey to human are very low. Less than 8% of cancer treatments make it from animal studies into a clinical setting, where they’re tested on people, and only 10% of the medications in those clinical trials make it through to government approval. No wonder some researchers joke about mice and monkeys lying and exaggerating.
The specification fails to make up for the deficiencies of the global scientific community.
Essentially, Applicant is requiring the ordinary artisans to discover for themselves that which Applicant fails to disclose.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
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.
9. Claims 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claims 1 and 7 recite a method of treating a disease or disorder in a subject, the method comprising the steps of:
i) administering to the subject a composition comprising a therapeutic agent (Claim 7, “standard dose”) and an inert agent, thereby achieving a corresponding therapeutic response; and
ii) repeating step (i) one or more times until the inert agent triggers a GRN response and a corresponding therapeutic response without the therapeutic agent, thereby treating the disease or disorder by administering the inert agent.
The Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejections.
With respect to Step 1, the claim is directed to a process, which is a statutory category of invention (Step 1: YES).
With respect to Step 2A, prong one, the judicial exception, the claims are directed to the administration of a therapeutic agent and an inert agent to a subject, in a method of treating a disease or disorder in said subject.
As discussed above, the claims encompass:
i) an enormously vast genus of radiological or thermal therapeutic agents, an essentially infinite genus of chemical therapeutic agent compounds, an essentially infinite genus of nucleic acid therapeutic agent compounds, and/or an essentially infinite genus of amino acid therapeutic agent compounds;
ii) an enormously vast genus of radiological or thermal inert agents, an essentially infinite genus of chemical inert agent compounds, an essentially infinite genus of nucleic acid inert agent compounds, and/or an essentially infinite genus of amino acid inert agent compounds;
iii) an enormously vast genus of disorders or conditions caused by mutation of essentially all genes to be treated;
iv) an enormously vast genus of therapeutic responses recited at a high level of generality to be achieved;
v) an enormously vast genus of structurally and functionally undisclosed gene regulatory networks comprising as few as 140 to as many as 95,000 different genes and their functional biological relationships, however directly or indirectly that might be, that are and/or are not to be triggered by the therapeutic agent and/or inert agent; and
vi) the enormously genus of prokaryotic and eukaryotic subjects, essentially all extant lifeforms on the planet, including about 1.6x10^6 species of prokaryotes and about 8.7 x10^6 species of eukaryotic organisms, such as protists, fungi, plants, and animals to be treated.
Instant specification fails to disclose a working example of the broadly claimed method.
Those of ordinary skill in the art immediately recognize that Applicant simply does not possess infinity!
Thus, at best, instant claims are directed to abstract thought.
The instant portion of the invention, as claimed, falls under the "germ of an idea" concept defined by the CAFC. The court has stated that "patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be workable". The court continues to say that "tossing out the mere germ of an idea does not constitute an enabling disclosure" and that "the specification, not knowledge in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". (See Genentech Inc v. Novo Nordisk A/S 42 USPQ2d 1001, at 1005).
Thus, the claimed limitations recited at a high level of generality is/are considered to be directed to one or more abstract ideas or mental thoughts performed by the artisan, and thus directed to a judicial exception (Step 2A, prong one: YES).
With respect to Step 2A, prong two, the claim does not recite additional elements that integrate the judicial exception into a practical application.
The claimed elements are recited at a high level of generality. The step(s) of administering the therapeutic and/or inert agent(s) is considered merely extra-solution activity within the medical and/or research field of use. It is thus extra-solution activity, and does not integrate the judicial exception(s) into a practical application (Step 2A, prong two: NO).
With respect to Step 2B, the not considered to recite additional elements that amount to significantly more than the judicial exception itself (Step 2B: NO).
Citation of Relevant Prior Art
10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cazzola et al (Escalation and De-escalation of Therapy in COPD: Myths, Realities and Perspectives, Drugs 75: 1575-1585, 2015) is considered relevant prior art for having taught that those of ordinary skill in the art have long-practiced de-escalation or step-down therapy in their daily clinical practice (e.g. pg 1576, col. 1, Key Points), whereby the practice of de-escalation of therapy is not surprising (e.g. pg 1576, col. 2). The possibility of escalating or de-escalating drug therapy is a consequence of the variation of disease being treated, the phenotypic response, and potential side effects (e.g. Figure 1, legend).
Isreal et al (Treatment De-Escalation in Patients With Inflammatory Bowel Disease, Gastroenterol. & Hepatol. 15(6): 335-341, 2019) is considered relevant prior art for having taught that treatments used to induce or maintain remission may not be required indefinitely. The associated side-effect profile, adverse events, and costs are additional motivators for the ordinary artisan to exercise de-escalation therapy and administer lowered doses of a therapeutic agent (e.g. Abstract; Figures 1-2; pg 340, Table).
Cazzola et al and Isreael et al differ from the instantly claimed method(s) in that they do not teach administering an inert agent to the subject that triggers a response in the gene regulatory network (GRN) and a corresponding therapeutic response, let alone in the absence of the therapeutic agent.
Conclusion
11. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638