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 .
Information Disclosure Statement
The information disclosure statement (IDS) filed on 1 November 2023 has been considered by the Examiner.
Status of the Claims
Original patent claims 1-16 are pending wherein claims 1, 2, 6, 9, 13, and 14 have been amended. Claims 17-23 are new.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 3-5, 7, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Duffy, Colm, Heteroaromatic Lipoxin A4 Analogues: Synthesis and Biological Evaluation, Springer-Verlag Berlin Heidelberg, 2012 (“Duffy”)(copy provided herewith).
Regarding claim 1, Duffy discloses a series of heteroaromatic lipoxin A4 analogues (pages 11-12). One of the heteroaromatic lipoxin A4 analogues contains a thiophene moiety as the B domain and has the following structure (pages 83-84, Fig. 2.1):
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Another of the heteroaromatic lipoxin A4 analogues contains an indole moiety as the B domain and has the following structure (page 110 – Fig.6.1):
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The thiophene-containing lipoxin A4 analog is the same as the claimed compound of formula (I) wherein “L” is a five-membered heterocyclic ring or benzo-fused five-membered heterocyclic ring, subscript “a” is equal to 1, R1 is a hydrogen atom, R2 is an alkoxy group, R3 is an alkyl group, and R4 is a methylene group (CH2). Likewise, the indole-containing lipoxin A4 analog is the same as claimed compound of formula (I) wherein “L” is a benzo-fused five-membered heterocyclic ring, subscript “a” is equal to 1, R1 is a hydrogen atom, R2 is an alkoxy group, R3 is an alkyl group, and R4 is a methylene group.
Regarding claim 3, the disclosed indole-containing lipoxin A4 analog is the same as claimed compound wherein “Z” is a nitrogen.
Regarding claim 4, the thiophene of the disclosed thiophene-containing lipoxin A4 analog corresponds to the claimed heterocyclic moiety wherein “V” is a sulfur atom, “W” is CR6 where R6 is a hydrogen atom, and “U” is CR7 where R7 is a hydrogen atom.
Regarding claim 5, the methoxy group present in both the disclosed thiophene- and the indole-containing lipoxin A4 analogues corresponds to the claimed C1 alkoxy group.
Regarding claim 7, the five carbon alkyl group of the A domain of the disclosed lipoxin analogs (See Fig. 2.1 of Duffy) corresponds to the claimed C5 alkyl group.
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Regarding claim 9, in the structure of thiophene LXA4 taught by Duffy (shown below), the circled hydroxyl group is disclosed as being racemic.
As such, Duffy teaches plainly teaches a thiophene lipoxin analog wherein the OH group at C15 is in the “R” configuration which meets the limitations of claim 9.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4, 5, 7-12, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Petasis, US 2005/0203184 (“Petasis”) in view of Duffy.
Regarding claims 1 and 9, Petasis discloses lipoxin analogs comprising an aromatic ring [abstract, 0007-0016]. Petasis teaches an example lipoxin analog having the following structure [0186, claim 5]:
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.
In the structure above, the group “A” may be a hydroxyl or alkoxy group (claim 5).
Petasis is silent regarding the lipoxin analogues comprising one of the claimed heterocyclic ring structures.
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Duffy discloses replacing certain functionalities of lipoxin A4 with chemically stable motifs with the aim of retaining lipoxin A4’s potent biological activity (page 11 – section 1.1).
Fig. 2.1 of Duffy illustrating the domains (A, B, & C) of native
lipoxin A4 which are targeted for modification.
Duffy teaches that derivatization of the triene structure (i.e., domain B) has major advantages in terms of considerably increasing the stability of the molecule towards enzymatic composition and prevention of double isomerization (page 17 – section 2.4). In an example, Duffy teaches replacing the triene domain of native lipoxin A4 with a heterocyclic or benzene ring (page 19, Fig. 2.4).
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Duffy goes on to teaches replacing the triene domain of lipoxin with thiophene and that thiophene is excellent bioisostere for benzene (page 83 - section 5.1). Duffy further teaches that bioisosteric replacement has had widespread success in the pharmaceutical industry as it has shown to prevent unwanted side effects in some drugs (page 83 – section 5.1). Duffy discloses an example of a lipoxin A4 analog wherein the triene domain has been replaced with a thiophene resulting the following structure (page 84 – Fig. 5.1):
Fig. 5.1 of Duffy illustrating the structure of the disclosed
thiophene analog of lipoxin A4.
Petasis and Duffy are both directed towards analogs of lipoxin A4. It would have been obvious to one of ordinary skill in the art at the time the instant invention was effectively filed have substituted the benzene ring of the lipoxin analog disclosed by Petasis with a thiophene as taught by Duffy because thiophene was recognized in the art as being an excellent bioisostere for benzene. Additionally, it would have been obvious to make the above described modification of the lipoxin analog of Petasis with the expectation of preventing unwanted side effects. The substitution of the benzene ring of the lipoxin analog of Petasis with a thiophene group would have produced a compound which is the same as claimed compound of formula (I) wherein “L” is a five-membered heterocyclic ring, subscript “a” is equal to 1, R1 is a hydrogen atom, R2 is an alkoxy group, R3 is an alkyl group, and R4 is a methylene group.
Regarding claim 4, the thiophene of the lipoxin A4 analog of modified Petasis would have corresponded to the claimed heterocyclic moiety wherein “V” is a sulfur atom, “W” is CR6 where R6 is a hydrogen atom, and “U” is CR7 where R7 is a hydrogen atom.
Regarding claim 5, Petasis teaches embodiments of the disclosed lipoxin analog wherein the “A” group is a methoxy group which corresponds to the claimed C1 alkoxy group [0186].
Regarding claim 7, the five carbon alkyl group of the A domain (See Fig. 2.1 of Duffy) corresponds to the claimed C5 alkyl group.
Regarding claim 8, Petasis is silent regarding the presence of a phenoxy group as claimed. However, Petasis teaches that the disclosed lipoxin A4 analog is useful for ameliorating or treating diseases or conditions associated with undesired cell proliferation such as cancer [0172]. Duffy teaches that replacing the alkyl group of the A domain of lipoxin with a p-fluorophenoxy group has shown potential as an ani-cancer agent as it inhibits endothelial cell proliferation leading to suppressed angiogenesis (page 13 – section 2.3)
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Fig. 2.3 of Duffy illustrating the modification of domain A
of lipoxin with a p-fluorophenoxy group.
As such, in light of the teachings of Duffy, it would have been obvious to one of ordinary skill in the art to have further modified the lipoxin analog of modified Petasis by replacing the alkyl group of the A domain with a fluorophenoxy group. The compound that would have been produced by substituting a p-fluorophenoxy group for alkyl group in domain A of the lipoxin analog of modified Petasis would have produced a compound which meets the limitation of claim 8 where in R7 is a fluorine atom.
Regarding claims 10 and 11, Petasis teaches a medicament formulation comprising a lipoxin analog and a lubricant [0122, 0129].
Claims 12 and 15, Petasis teaches using the lipoxin analogs to treat asthma [0159].
Claims 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Petasis in view of Duffy as applied to claims 1 and 10 above, and further in view of Gjorstrup, US 2008/0161275 (“Gjorstrup”).
Regarding claims 12-16, Petasis taken in combination with Duffy teaches what is described above. Additionally, Petasis teaches that the disclosed lipoxin analogs are useful for treating inflammation [abstract, 0007]. Likewise, Duffy teaches that the disclosed heteroaryl analogs of lipoxin A4 have been designed with the view of increasing the biological potency of these anti-inflammatory agents (page 109 – section 6.1).
Modified Petasis is silent regarding a method of treating the disease or condition recited in claims 12-16.
Gjorstrup discloses a method of treating inflammatory diseases comprising administering a glucocorticoid conjointly with a lipoxin compound [abstract, 0006-0009, 0019]. The lipoxin compound may be an aromatic lipoxin analog [0309-0315]. Gjorstrup teaches that the inflammatory disease being treated may be an inflammatory condition including atherosclerosis or a vascular disease associated with diabetes [0013]. Gjorstrup further teaches treating asthma and glomerulonephritis with the disclosed composition which corresponds to the asthma and glomerulonephritis [0013, 0014].
The person of ordinary skill would be motivated to combine the teachings of Petasis, Duffy, and Gjorstrup to arrive at the instantly claimed invention as all of the teachings are drawn to lipoxin analogues and their use for the treatment of disease, especially inflammatory conditions. There would be a reasonable expectation of success as the use of one lipoxin analogue for another would conserve the utility of the method of treating inflammation. The treatment of an inflammatory condition including atherosclerosis corresponds to the treating recited in claims 12 and 13. The treatment of a vascular disease associated with diabetes corresponds to the treating of macrovascular or microvascular complication associated with diabetes recited in claim 14. The treatment of asthma or glomerulonephritis corresponds to the claimed treatment of asthma and glomerulonephritis recited in claims 15 and 16, respectively.
Allowable Subject Matter
Claims 2, 6, and 17-23 are 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.
Related Proceedings
Applicant is reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceedings in which U.S. Patent No. 11,161,824 is or was involved. These proceedings would include any trial before the Patent Trial and Appeal Board, interferences, reissues, reexaminations, supplemental examinations, and litigation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEE E SANDERSON whose telephone number is (571) 270-1079. The examiner can normally be reached M-F: 9:30AM to 7:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Patrica Engle can be reached at (571) 272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEE E SANDERSON/
Patent Reexamination Specialist, Art Unit 3991
Conferees:
/JOSEPH R KOSACK/Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991