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 1-20 and 22-23 are pending in the instant application.
Claim 21 has been canceled.
Election/Restriction
This action is in response to an election from a restriction requirement filed on June 18th, 2026. There are 22 claims pending and 11 claims under consideration. Claims 11-18, 20, and 22-23 have been withdrawn as claims drawn to a non-elected invention. This is the first action on the merits. The present invention relates to a pentamidine analog of the general Formula (1a).
Applicant’s election without traverse of Group I, Claims 1-10 and 19 and species election of
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as a single species of pentamidine analog in the reply received August 14th, 2026 is acknowledged. Therefore, this restriction is considered proper and thus made FINAL.
The elected species was found to be free of the prior art. Thus, examination was extended to all species of pentamidine analogs of Formula (1a) as recited at instant Claim 1.
Domestic Benefit
Acknowledgement is made of Applicant’s claim for domestic benefit based on the U.S. Provisional Application No. 63/276,473 filed November 5th, 2021. Claims 1-10 and 19, presently under examination, are fully supported by this application and will be evaluated with an effective filing date of November 5th, 2021.
Information Disclosure Statement
The Information Disclosure Statements received May 7th, 2024, March 7th, 2025, and October 8th, 2025 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
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 May 2nd, 2024. These drawings are acceptable.
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 1-10 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a pentamidine analog having the general Formula (1a) in which Y1 or Y1 and Y2 independently are selected from H, C1-3 alkyl optionally substituted with halogen or phenyl, amino, halogen, pyrrolidinyl, or phenyl, or Y1 and Y2 together with X form a 5-7 membered hydrocarbon ring, Z is phenyl optionally substituted with halogen, and R+1+ to R4 are independently hydrogen or methyl, does not reasonably provide enablement for pentamidine analogs of Formula (1a) in which Y1, Y2, Z, and R1 to R4 are otherwise defined. 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 nature of the invention is drawn to a pentamidine analog having Formula (1a) as recited at instant Claim 1.
Breadth of the invention:
The scope of the claimed invention is broad, as it is drawn to compounds of the formula:
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allowing for myriad combinations of the variables recited thereof.
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 representing a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, the 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 compound in which Y1, Y2, Z, or R1 to R4 were defined as anything other than those definitions noted above in the instant application.
Within the specification, “specific operative embodiments or examples 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 the 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.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 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.
Claim 1 is indefinite due to the recitation of the limitation “Y is Y1 and Y2 when X is C, or -CH-CH-.” This limitation renders the claim indefinite due to defining a single variable, Y, by two distinct variables, Y1 and Y2. It is unclear as to whether, when X is C, Y1 and Y2 are both bound to C, or if Y2 may be bound to Y1. Similarly, when X is -CH-CH-, it is unclear as to whether Y1 and Y2 must be bound to each of the two carbon atoms defining X. The examiner has interpreted this limitation such that when X is C, Y1 and Y2 are both bound to C, and when X is -CH-CH-, Y1 is bound to one carbon atom, and Y2 is bound to the second carbon atom. Appropriate clarification is required.
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, 3, 9, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Parrish et. al., (“Structure-Activity Relationships for the Inhibition of Acrosin by Benzamide Derivatives”, Journal of Medicinal Chemistry, 1978; hereinafter referred to as Parrish).
At Page 1133, Parrish teaches compounds of the formula:
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Parrish teaches compound 32 as defining the above variables such that n is 5, R1 is Am, R2 is H, R3 is I, R4 is H, R5 is I, R6 is Am, and R7 is H. In the footnote of Table II, Parrish notes that “AM = -C(=NH)NH2. For clarity of the record, the full structure of this compound is:
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This compound reads on a pentamidine analog of the Formula (1a) when the variables are defined as follows:
X is C.
Y is Y1 and Y2, wherein Y1 and Y2 are each H.
Z is phenyl, substituted with halogen, wherein halogen is iodo.
R1 to R4 are each H.
Regarding Claim 19, at Page 1135, Second Paragraph of Second Column, Parrish teaches assay mixtures were subjected to various concentrations of the inhibitors studied. This would include a composition of compound 32, above.
Claims 1, 3, 9-10, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tidwell et. al., (“Analogues of 1,5-Bis(4-amidinophenoxy)pentane (Pentamidine) in the Treatment of Experimental Pneumocystis carinii Pneumonia”, Journal of Medicinal Chemistry, 1990; hereinafter referred to as Tidwell).
At Page 1253, at Scheme I, Tidwell teaches the following structures:
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,
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, and
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At Page 1254, Tidwell defines compound 15 such that n is 5, R is Br, and the “am” groups are in the para position. Compound 18 is defined such that n is 5, R is methoxy, and the “am” groups are in the para position. Compound 21 is defined such that n is 5. Compound 26 is defined such that n is 5. Compound 27 is defined such that n is 6.
For clarity of the record, the full structure of compound 15 is:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is C.
Y is Y1 and Y2, wherein each of Y1 and Y2 are H.
Z is phenyl, substituted with halogen, wherein halogen is bromo.
R1 to R4 are each H.
For clarity of the record, the full structure of Compound 18 is:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is C.
Y is Y1 and Y2, wherein each of Y1 and Y2 are H.
Z is phenyl, substituted by lower alkoxy, wherein alkoxy is methyl.
R1 to R4 are each H.
For clarity of the record, the full structure of Compound 21 is:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is C.
Y is Y1 and Y2, wherein each of Y1 and Y2 are H.
Z is phenyl, substituted by nitro.
R1 to R4 are each H.
For clarity of the record, the full structure of Compound 26 is:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is C.
Y is Y1 and Y2, wherein each of Y1 and Y2 are H.
Z is phenyl, substituted by amino.
R1 to R4 are each H.
For clarity of the record, the full structure of Compound 27 is:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is -CH-CH-.
Y is Y1 and Y2, wherein each of Y1 and Y2 are H.
Z is phenyl, substituted by amino.
R1 to R4 are each H.
Regarding Claim 19, at Page 1257, First Paragraph of Second Column, Tidwell teaches administration of the above compounds via IV injection in which the compounds were dissolved in saline.
Claims 1, 3, 9, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Berger et. al. (“Hydroxylation of Pentamidine by Rat Liver Microsomes”, The Journal of Pharmacology and Experimental Therapeutics, 1990; hereinafter referred to as Berger).
At Page 887, Berger teaches the following compound:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is C.
Y is Y1 and Y2, wherein Y1 is H and Y2 is hydroxyl.
Z is phenyl.
R1 to R4 are each H.
Regarding Claim 19, compositions of this compound are taught at Page 888, Table 1.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry File 1358160-77-6 (entered into STN February 29th, 2012; hereinafter referred to as CAS Registry File).
CAS Registry File teaches a compound of the following formula:
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This compound reads on a pentamidine analogue of Formula (1a) as recited at instant Claim 1 when the variables are defined as follows:
X is N.
Y is Y1, wherein Y1 is methyl.
Z is phenyl, substituted twice with methoxy.
R1 to R4 are each H.
Conclusion
Claims 1-10 and 19 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.J.B./ Examiner, Art Unit 1624
/BRENDA L COLEMAN/ Primary Examiner, Art Unit 1624
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