Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-2, 4, 10, 13, 15-16, 22, 24-25, 31-34, 37, 40, 43, 45, 50, 52, 96-97, and 106-107 are pending in the instant application.
Claims 3, 5-9, 11-12, 14, 17-21, 23, 26-30, 35-36, 38-39, 41-42, 44, 46-49, 51, 53-95, 98-105, and 108-123 have been canceled.
Domestic Benefit
Acknowledgement is made of Applicant’s claim for domestic benefit based on the U.S. Provisional Application No. 63/165,592 filed March 25th, 2021. The instant claims are fully supported by this application, and will be evaluated with an effective filing date of March 25th, 2021.
Information Disclosure Statement
The Information Disclosure Statements received on September 21st, 2023 and February 26th, 2025 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
The disclosure is objected to because of the following informalities:
The synthetic schemes in Paragraphs [00335], [00339], [00343], [00347], [00355], [00361], [00391], [00413], [00415], and [00419] have been cut off.
Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
Acknowledgement is made of the drawings received September 21st, 2023. These drawings are acceptable.
Claim Rejections – Improper Markush Grouping
Claims 1-2, 4, 10, 13, 15-16, 22, 24-25, 31-34, 37, 40, 43, 45, 50, 96-97, and 106 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of a compound having a structure represented by formula I or II as recited at instant Claim 1 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The Markush grouping is directed to compounds of Formula I or Formula II. These formulas are:
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wherein the variables R1-4 and R7-8 can be any of a plurality of moieties as recited at the claims, which include groups that are further substituted with, for example, “-[L]-diagnostic moiety”, which is inclusive of a myriad of distinct chemical moieties. Further, “A” is broadly defined as a therapeutic moiety at instant Claim 1, with no further limitations defining the types of moieties that are suitable for compounds of Formula I or II, thereby allowing for virtually limitless compounds meeting these requirements with no significant structural element shared amongst them.
The result is a group of compounds that include monocyclic, bicyclic, or polycyclic ring systems that share no significant structural similarity. This grouping includes compounds that are not obvious variants of each other. To this end, a comparison of example compounds 5’, found at Page 104 of the instant specification, with compound 37, found at page 147 of the instant specification demonstrates such a lack of significant structural similarity, as these compounds are not obvious variants of each other:
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To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claims 1-2, 4, 10, 13, 15-16, 22, 24-25, 31-34, 37, 40, 43, 45, 50, 96-97, and 106 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 compound of Formula I or II wherein R1 is hydrogen, R2-4 are hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or halogen, and R7 and R8 are C1-8 alkyl, C3-10 carbocyclycl, or R7 and R8together from a 4-to-7-membered heterocyclyl comprising 1 to 2 heteroatoms selected from N or O, does not reasonably provide enablement for compounds of Formula I or II in which R1-4 and R7-8 are defined as variables other than these. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a compound having a structure represented by formula I or formula II.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to any compounds of the formulas:
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allowing not only for a myriad of substituents recited as definitions for R1-4 and R7-8-, but also the broadly defined “linking group”, “diagnostic moiety”, and “therapeutic moiety”.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts thereof where R1-4 and R7-8 were not defined as mentioned above in the present application.
Within the specification, “specific operative embodiments of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
Claims 52 and 107 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.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of Formula III or IV.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to any compounds of the formulas:
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allowing not only for a myriad of substituents recited as definitions for R1-4 and R7-8-, but also the broadly defined “linking group”, “diagnostic moiety”, and “therapeutic moiety”.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Applicant has provided no working examples of a compound of formula III or a compound of formula IV. Beginning at Page 59 of the instant specification, Applicant has provided structures of a compound of formula (III), listing variables R1-4 and A. Further, at Page 60, structures are provided with the generic labels of, for example, “Therapeutic Moiety”, “Diagnostic Moiety”, and “LG”. Similarly, Applicant presents structures for compounds of formula (IV) beginning at Page 67 of the instant specification. As above, these structures include the variables R1-4 and “A”. Further, beginning at page 68 of the instant specification, Applicant provides structures of compounds of formula IV using generic labels like “Diagnostic Moiety” and “Therapeutic Moiety”.
Nowhere in the instant disclosure has Applicant provided a specific example with sufficient characterization data of a compound of formula III and/or formula IV, with all variables fully defined. As presented, Applicant has disclosed speculative examples of compounds of a generic formula III or formula IV, with ambiguous labels leading to innumerable compounds that could be encompassed by this formulas to be envisaged by a person having ordinary skill in the art. Insufficient guidance has been provided for a person having ordinary skill in the art to understand, for example, which moieties should be selected as a “diagnostic moiety” or a “therapeutic moiety” to be included as a part of a compound III or IV, nor would it be readily understood based on the instant disclosure the motivation for selecting a particular moiety that could satisfy this broad characterization.
Within the specification, “specific operative embodiments of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
Claim 97 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 treating lung cancer, skin cancer, and pancreatic cancer, does not reasonably provide enablement for treating any disease or disorder characterized by, or associated with or exhibiting tissue hypoxia. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of treating a disease or disorder characterized by, or associated with or exhibiting tissue hypoxia.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to the treatment of any disease or disorder characterized by, or associated with or exhibiting tissue hypoxia. This covers a myriad of diseases or disorders with mutually exclusive and distinct etiologies. Further, the method is drawn to administration of any compound of formula I or II. Additionally, this covers an array of diseases or disorders, both known presently, or diseases or disorders discovered years from now that are associated with tissue hypoxia. Can an Applicant simply “reach through” and obtain patent protection for diseases yet unknown, or diseases currently known, but later are classified as being associated with tissue hypoxia?
Further, at Page 87, Paragraph 00239 of the instant specification, Applicant is clear that the invention is drawn to the treatment of cancer, in general.
Level of ordinary skill in the art:
No compound has ever been found to treat cancers of all types generally. Since this assertion is contrary to what is known in medicine, proof must be provided that this revolutionary assertion has merits. The existence of such a “silver bullet” is contrary to our present understanding of oncology. The state of the art is not indicative of any pharmaceutical agents that are useful in the treatment of cancer generally. At Page 1004, Cecil Textbook of Medicine states that “each specific type has unique biologic and clinical features that must be appreciated for proper diagnosis, treatment and study”. Different types of cancers affect different organs and have different methods of growth and harm to the body. Also see In re Buting, 163 USPQ 689 (CCPA 1969), wherein ‘evidence involving a single compound and two types of cancer, was held insufficient to establish the utility of the claims directed to disparate types of cancers’. Thus, it is beyond the skill of oncologists today to get an agent to be effective against cancers generally.
A similar statement appears at In re Application of Hozumi et. al., 226 USPQ 353: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. This is because it is now understood that there is no “master switch” for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body’s cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environmental factors.
Similarly, In re Novak, 134 USPQ 335, 337-338 says “unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them.” There is no such evidence in this case for a compound that treats all types of cancer. Likewise, In re Cartright, 49 USPQ2d 1464, states: “Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient” does what the specification surmises that it does. That is exactly the case here. Moreover, even if Applicant’s assertion that cancer in general could be treated with these compounds were plausible -- which it is not --, that “plausible” would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success.
Recently, Wu et. al. (“Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA- approved novel therapeutic drugs for solid tumors from 1991 to 2021; Journal of Hematology & Oncology, 15, 143, 2022; hereinafter referred to as Wu), at the Abstract, discloses that between 1991 and 2021 there have been 228 new cancer drugs approved by the U.S. Food and Drug Administration of which 120 of these are drawn to the treatment of solid tumors alone. At Page 5, Table 1 Wu teaches that there are 21 different approved drugs for treating lung cancers, some of which have cellular targets. At Page 10, Table 2, Wu teaches breast cancer has 22 different drugs that have varied cellular targets and are indicated for different types of breast cancer. At Page 17, Table 4, Wu teaches there are 17 different drugs available to treat different forms of gastrointestinal cancers. At Page 38, Figure 12, Wu summarizes the protein structure of some cellular targets and the binding site of their respective drugs. Taken together, Wu teaches that no single therapeutic has ever been identified as a treatment for all forms of cancer; and closer examination of Figure 12 provides a logical explanation. As highlighted in Figure 12, molecular protein targets implicated in different cancers (e.g. EGFR for lung cancer in Table 1, VEGFR2 for gastric cancer in Table 4) have different three-dimensional protein structures, different active sites, and therefore require different drugs with the right shape and chemical groups in order to bind the target active site and have an effect in treating cancer. In other words, there is no one size fits all approach to treating cancer simply for the reason that no single molecule will have the shape and chemical functional groups necessary to bind and modulate all modular targets of cancer, all of which have varied shapes. It is commonly known in the pharmaceutical arts that shape dictates function wherein drugs which have a shape complimentary to the protein target will bind and have an effect (this is often referred to simplistically as a “Lock and Key” model). Given the varied shape of protein targets in cancer (e.g. EGFR and VEGFR2), it is pure fantasy to speculate that a single drug with a single three dimensional shape will bind all protein targets implicated in cancer therapy and have an effect in treating all forms of the disease. As such, at present the “silver bullet” drug therapy to treat all forms of cancer is elusive and such a therapy is not recognized in the art where the reality is that different forms of cancer require different drug therapies.
The amount of direction provided and working examples:
Beginning at page 157, Example 77, of the instant specification, Applicant discloses the methods employed for a variety of biological testing of the instantly claimed compounds.
In terms of utility in treating a disease, protocol for testing the instantly claimed compounds in cell viability assays for H460 and A341 cells, which are, respectively a lung cancer cell line and a skin cancer cell line. Figure 3E demonstrates the efficacy of an instantly claimed compound, compound 37 in treating a skin cancer cell line. Figure 3F provides data of the same compound in treating a lung cancer and a skin cancer cell line.
Beginning at Page 163, Applicant discloses the methods for a Bx-PC3 xenograft tumor model. The Bx-PC3 cell line is a pancreatic cancer cell line. The results thereof are shown, for example, at Figures 5A and 5B.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As referenced above, a person having ordinary skill in the art would need not only to identify and/or develop suitable methods for determining the efficacy of the instantly claimed compounds in treating disorders or diseases other than lung cancer, skin cancer, or pancreatic cancer, but would also need to employ these methods, with no reasonable expectation of success.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
The specification fails to provide enough support for the broadly claimed method of treating a disease or disorder associated with hypoxia.
Genentech Inc v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine the efficacy of treatment of diseases or disorders other than those mentioned above, with no assurance of success.
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 1-2, 22, 31-33, 43, 45, 52, 97, and 106-107 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 1-2, 22, 31-33, 43, 52, and 97 are rendered indefinite for the recitation of limitations of “linking group”, “diagnostic moiety”, “inductive electron withdrawing group”, “π-electron withdrawing group”, “leaving group”, and “therapeutic moiety.” The claim language in view of the instant application are insufficient for a person having ordinary skill in the art to readily understand the metes and bounds of these limitations. No definition is provided for “linking group” in the instant specification. A person having ordinary skill in the art could readily ascertain a myriad of moieties that would qualify, broadly, as a “linking group.” This is insufficient, however, for a person having ordinary skill in the art to readily understand which linking groups are intended to be encompassed by the instant claims. The terms “π-electron withdrawing group”, “inductive electron withdrawing group”, “therapeutic moiety”, and “diagnostic moiety” are defined at Page 19, Paragraphs 0060, 0061, 0064, and 0065, respectively. In each of these cases, the definition provided is insufficient for a person having ordinary skill in the art to understand the metes and bounds of these limitations, as the specific moieties intended to be encompassed by this claim language are ambiguous. Appropriate clarification is required.
Claims 106-107 recite the limitations "R1, R2, R3, R4, R7, R8, and A" in the various formulas recited. There is insufficient antecedent basis for these limitations in the claims, as these variables have not been defined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 13, 22, 40, and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bernier et. al. (“Improved Procedure for the Synthesis of Enamine N-Oxides”, J. Org. Chem., 2008; cited on Applicant’s Information Disclosure Statement filed September 21st, 2023; hereinafter referred to as Bernier) as evidenced by Bickel (“The Pharmacology and Biochemistry of N-Oxides”, Pharmacological Reviews, 21, 1969; hereinafter referred to as Bickel).
At Page 4229, Figure 1, Bernier teaches the following compounds:
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Fully drawn out, compound 1ab is:
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This compound reads on a compound of formula I as recited at Claim 1 when the variables are defined as follows:
R1 is hydrogen.
R2 is hydrogen.
R3 is hydrogen.
R4 is hydrogen.
R7 is methyl.
R8 is methyl.
A is absent.
Regarding the limitation “provided that the compound of formula (I or II) contains at least one –[L]-diagnostic moiety or therapeutic moiety”, Bickel teaches at page 327 that “Several N-oxides have become pharmacological agents used in therapy (alkaloids, chemotherapeutics, antibiotics, psychotropic drugs)”. Therefore, under the broadest reasonable interpretation of requiring a compound of formula I contains a therapeutic moiety, the enamine moiety itself is recognized in the art as a therapeutic moiety.
Conclusion
Claims 1-2, 4, 10, 13, 15-16, 22, 24-25, 31-34, 37, 40, 43, 45, 50, 52, 96-97, and 106-107 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624