DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The present Application, filed June 9, 2023, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/US2021/065304, filed December 28, 2021, which claims priority to U.S. Provisional Patent Application No. 63/131,133, filed December 28, 2020.
Status of the Claims
In the amendment filed June 9, 2023, claims 4-14, 16-27, 36, and 39 are canceled and new claims 40-47 are added. Claims 1-3, 15, 28-32, 34-35, and 37-38 are amended. Claims 1-3, 15, 28-35, 37-38, and 40-47 are currently pending.
Information Disclosure Statement
The two total information disclosure statements (IDSs) submitted on June 9, 2023 and March 7, 2025 are acknowledged.
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.
Claims 1-3 and 15 are anticipated by Lee:
Claims 1-3 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the non-patent publication, Chemistry and Biology of Macrolide Antiparasitic Agents, J. Med. Chem., 54, pgs. 2792-2804 (2011) by Lee et al. (hereinafter, “Lee”).
Claim 1 recites a compound of Formula I
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where the variable moieties are as defined. In particular, X, Y, and Z are oxygen, and R and R1-R4 can each independently be hydrogen, methyl, ethyl, and methoxy, among other alternatives.
Lee teaches an analysis of the structure-activity relationships of various macrolides, particularly erythromycin and analogues (Abstract). As part of this, Lee reviews the structures of erythromycin and clarithromycin (e.g. Figure 1A)
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Erythromycin and clarithromycin, as shown by Lee, is each a compound of instant Formula I of instant claim 1, where the eighteen R groups are a combination of H, OH, CH3, and C2H5; the eight R1 groups are a combination of H, OH, CH3, and OCH3; the four R2 groups are a combination of H, and CH3; R3 and R4 are each CH3; and R5 is H.
Claim 2 recites a compound of Formula II
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where the variable moieties are as defined. In particular, X, Y, and Z are oxygen, and R and R1-R4 can each independently be hydrogen, methyl, ethyl, and methoxy, among other alternatives, and R8 can be H or C1-10 alkyl.
With respect to claim 2, Lee further reviews the structure of azithromycin (e.g. Figure 1A)
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Azithromycin, as shown by Lee, is a compound of instant Formula II of instant claim 2, where the twenty R groups are a combination of H, OH, CH3, and C2H5; the eight R1 groups are a combination of H, OH, CH3, and OCH3; the four R2 groups are a combination of H, and CH3; R3 and R4 are each CH3; and R5 is H.
Claim 3 depends from claim 1 and specifies narrower sets of alternatives for certain variable moieties. With respect to claim 3, as noted, the instant R groups of Formula I in the erythromycin and clarithromycin of Lee are a combination of H, OH, CH3, and C2H5. Because claim 3 requires that only one of elements (i)-(vi) be satisfied, and element (i) requires only that any R group be H, OH, CH3, OCH, or C2H5, any single instant R group of erythromycin or clarithromycin satisfies the requirements of claim 3.
Similarly, claim 15 depends from claim 2 and specifies narrower sets of alternatives for certain variable moieties. With respect to claim 15, as noted, the instant R groups of Formula I in the azithromycin of Lee are a combination of H, OH, CH3, and C2H5. Because claim 3 requires that only one of elements (i)-(vi) be satisfied, and element (i) requires only that any R group be H, OH, CH3, OCH, or C2H5, any single instant R group of azithromycin satisfies the requirements of claim 3.
Claims 1-3, 15, 30-35, 37, and 40-46 are anticipated by Lin:
Claims 1-3, 15, 30-35, 37, and 40-46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Application Publication No. 2009/0233888 to Lin (hereinafter, “Lin”).
Lin teaches a method for treating a disease condition in a mammal with an elevated level of bacteria-derived hydrogen sulfide (H2S) (paragraph [0001] and claim 1). The method of Lin comprises administering a therapeutic agent capable of at least partially eradicating the bacterial overgrowth, to reduce the level of bacteria-derived H2S, to the mammal (paragraph [0014] and claim 1). Lin further teaches that the therapeutic agent can be an agent that increases the mammal's phase III interdigestive intestinal motility and combinations thereof (claim 5), such as a prokinetic agent (claim 12), such as erythromycin or azithromycin (claim 13).
As noted above, the erythromycin of Lin is a compound of instant claims 1 and 3 and the azithromycin of Lin is a compound of instant claims 2 and 15.
With respect to claims 30 and 40, Lin further teaches that the therapeutic agent can be delivered in a therapeutically effective amount, as part of a formulation having a pharmaceutically acceptable carrier (paragraph [0067]). Such a formulation having erythromycin or azithromycin and a pharmaceutically acceptable carrier would thus be a pharmaceutical composition of instant claim 30 or 40.
With respect to claims 31-33 and 41-43, Lin teaches that the disease to be treated can be idiopathic pulmonary fibrosis (a fibrotic disease, see Lin, paragraph [0035] and claim 2). Lin thus teaches a method of treating a fibrotic disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of erythromycin or azithromycin (claims 31 and 41), while the specific treatment of idiopathic pulmonary fibrosis anticipates the specific element of claims 32-33 and 42-43. In addition, with respect to claims 34-35 and 44-45, the method of treating idiopathic pulmonary fibrosis as taught by Lin constitutes the method of treating an inflammatory disease of claims 34-35 and 44-45 (note that instant claims 35 and 45 indicate that pulmonary fibrosis is a recited inflammatory disease).
With respect to claims 37 and 46, Lin teaches that the disease to be treated can be cancer (paragraph [0035] and claim 2). Lin thus teaches a method of treating cancer in a subject, the method comprising administering erythromycin or azithromycin to the subject.
Claims 1, 3, 15, 30, 37-38, 40, and 46-47 are anticipated by Narita:
Claims 1, 3, 15, 30, 37-38, 40, and 46-47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 5,795,871 to Narita et al. (hereinafter, “Narita”).
Narita teaches that 14- or 15-membereed ring macrolide compounds, such as clarithromycin have a potent antitumor effect on non-small cell lung cancers (Abstract). Narita thus teaches a pharmaceutical composition for the treatment of non-small cell lung cancers (NSCLC) comprising an effective amount of a compound represented by Formula (I) Example 45 Synthesis of azithromycin 11,2’-dilipoate
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where the variable moieties are as defined. Formula (I) of Narita has significant overlap with instant Formulae I and II, and Narita teaches that preferably compounds of Formula (I) include erythromycin, clarithromycin, and azithromycin (col. 5, lines 36-47). Because, as noted above, these are compounds of instant Formulae I and II claims 1-3, and 15 are anticipated.
Narita further teaches the disclosed compounds can be used as dosage forms for the treatment of NSCLC by combining them with pharmaceutically acceptable carriers (col. 6, lines 6-28), and thus discloses pharmaceutical compositions of instant claims 30 and 40.
With respect to instant claims 37-38 and 46-47, Narita teaches a method for the treatment of NSCLC in a human, comprising administering to the human an effective amount of a compound represented by the disclosed Formula (I) (col. 2, lines 53-56, and claim 1). Claims 37-38 and 46-47 are therefore anticipated.
Claims 1, 3, 15, 30, 37-38, 40, and 46-47 are anticipated by Pietrzik:
Claims 1, 3, 15, 30, 37-38, 40, and 46-47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by International Patent Application Publication No. WO2018161039 to Pietrzik et al. (hereinafter, “Pietrzik”).
Pietrzik teaches various compounds having anti-inflammatory, anti-cancer, and anti-bacterial activity (Abstract), such as macrolide-based compounds of Formula 2
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where the variable moieties are as described. Pietrzik Formula 2 has significant overlap with instant Formulae I and II. In a working example, Pietrzik teaches Compound E-77,
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a 2′-lipoate ester of azithromycin that is identical to the fifteenth listed compound of instant claim 29 (also referred to in the instant specification as AO-02-45), depending from claim 2. Pietrzik compound E-77 is thus a compound of instant claims 2 and 29. Pietrzik compound E-77, as an azithromycin derivative and for the same reason as the azithromycin above, is also a compound of claim 15 because, for example, multiple groups corresponding to instant R are hydrogen.
Allowable Subject Matter
Claim 28 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629