DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status
Pursuant to preliminary amendments filed 12 June 2024, claims 21-37 are under current examination. As discussed below, misnumbered claims 29-36 have been renumbered 30-37, due to a duplicate claim 29.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Applicant’s preliminary amendment claim listing includes a duplicate claim 29, and therefore the second claim 29 has been renumbered as claim 30 and the subsequent claims have been renumbered as one number higher.
Thus, misnumbered claims 29-36 have been renumbered 30-37, resulting in claims 21-37 being under current examination.
Duplicate Claim Warning
Applicant is advised that should claim 27 be found allowable, claim 36 (misnumbered 35) will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
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 36 (misnumbered 35) 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 36 (misnumbered 35) recites the limitation "the proton pump inhibitor" in line 2. There is insufficient antecedent basis for this limitation in the claim.
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 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 21-25 and 29-33 (misnumbered 29-32) is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Depui et al. (U.S. Patent No. 6,136,344; issued 24 October 2000) in view of Borody (U.S. Patent No. 6,489,317; issued 03 December 2002) and Jahagirdar et al. (US 2009/0028940 A1; published 29 January 2009).
Regarding claims 21 and 29, Depui et al. discloses an oral pharmaceutical dosage form (title) for oral use for treating disorders associated with Helicobacter infections (abstract) especially Helicobacter pylori infections (column 1 lines 14-18) wherein a capsule preparation comprises a proton pump inhibitor in the form of enteric coating layered pellets mixed with one or more antibacterial compounds in the form of granules or pellets (column 3 lines 42-47) wherein the antibacterial components may be formulated in the form of instant release formulations (column 3 lines 48-50) wherein the antibacterial granules are preferably smaller than 1 mm (column 11 lines 22-29) wherein the enteric coating pellets have a core size preferably of 0.1-2 mm (column 8 lines 20-22, 50-57) and coating thickness of at least 10 µm (column 10 lines 50-52) wherein the enteric coating layer makes the pellets insoluble in acidic media but disintegrates/dissolves in near neutral to alkaline media such as in liquids present in the proximal part of the small intestine (column 12 lines 12-17) wherein one or more enteric coating layers can be used and various suitable enteric coating layer polymers can be used (column 10 lines 10-22) wherein to obtain acceptable acid resistance the thickness of the enteric coating is approximately at least 10 µm, preferably more than 20 µm (column 10 lines 48-54) wherein the proton pump inhibitor can be omeprazole such as magnesium omeprazole (column 5 lines 1-10; claims 6-7) wherein the antibacterial compounds can be amoxicillin and rifamycins and salts and hydrates and combinations thereof (column 7 lines 12, 14, 37-41; claim 10) wherein the dosage forms are administered one to several times a day wherein each dosage form preferably comprises 10-80 mg proton pump inhibitor and generally comprises 0.1 mg to 1.2 g antibacterial compound(s) (column 12 line 61 to column 13 line 4) wherein a method for treatment of Helicobacter pylori infection in man comprises administering to a host in need thereof a therapeutically effective dose of the composition (claim 21).
Regarding the claimed recitation of release of at least 70% of the proton pump inhibitor is delayed from 120 to at least 240 minutes following oral administration, Depui et al. explicitly discloses that the enteric coating layer makes the pellets insoluble in acidic media (i.e., does not release proton pump inhibitor in acid) but disintegrates/dissolves in near neutral to alkaline media such as in liquids present in the proximal part of the small intestine (i.e., disintegrates/dissolves in near neutral to alkaline media) (column 12 lines 12-17), which appears to satisfy the claimed release delay time. Furthermore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to vary the number of enteric coating layers, to vary/select the enteric coating layer polymer, and to vary the enteric coating layer thickness, in order to obtain the desired acid resistance and disintegration/dissolving in near neutral to alkaline media, as suggested by Depui et al., with a reasonable expectation of success, such that the instantly claimed release delay time is satisfied.
Depui et al. does not disclose an effective period of time, that the rifamycin is rifabutin, or that the pellets/granules are minitablets, as claimed.
Borody discloses a pharmaceutical composition for the treatment of gastrointestinal disorders associated with H. pylori infection including a first antibiotic of rifabutin, a second antibiotic such as amoxicillin, and a proton pump inhibitor (claims 1, 5) wherein the proton pump inhibitor may be omeprazole (claim 2) wherein a preferred combination is rifabutin, amoxicillin, and a proton pump inhibitor such as omeprazole (column 3 lines 41-45) wherein for oral administration the pharmaceutical composition may be in capsule form (column 4 lines 4-8) wherein treatment is continued until eradication of the H. pylori infection has been completed where usually treatment is continued for from 3-14 days (column 5 lines 7-16) wherein typical daily dosages are about 50-2000 mg rifabutin and about 100-5000 mg amoxycillin (column 4 line 62 to column 5 line 1).
Jahagirdar et al. discloses a pharmaceutical composition comprising antibiotic and having immediate release and controlled release entities, which can be used to treat helicobacter pylori (abstract; paragraphs [0008], [0083]) wherein the entities refer interchangeably to granules, pellets, beads, minitablets, and the like (paragraph [0026]).
It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to combine the teachings of Depui et al., Borody, and Jahagirdar et al. by making the composition of Depui et al. as discussed above and practicing the method of Depui et al. as discussed above using the combination of rifabutin, amoxicillin, and omeprazole and by continuing the oral treatment of Depui et al. for 3-14 days until eradication of the H. pylori infection has been completed as suggested by Borody, and by substituting the minitablet forms of Jahagirdar et al. for the pellet and granule forms therein, with a reasonable expectation of success. A person of ordinary skill in the art at the time the invention was made would have been motivated to do so: 1) to use a combination of active ingredients known to be a preferred combination for treating H. pylori per Borody given that rifabutin is a rifamycin, which Depui et al. suggests as an antibacterial compound, 2) to achieve eradication of the infection as suggested by Borody, and 3) given that minitablet, pellet, and granule forms are all interchangeable entities used in antibiotic compositions having immediate release and controlled release entities for treatment of helicobacter infections as suggested by Jahagirdar et al. As noted in MPEP 2144.06(II), it is prima facie obvious to substitute equivalents known for the same purpose.
Further regarding claim 21, Depui et al. discloses each dosage form preferably comprises 10-80 mg proton pump inhibitor and generally comprises 0.1 mg to 1.2 g antibacterial compound(s) (column 12 line 61 to column 13 line 4), which overlaps the claimed amounts of 12.5 mg rifabutin, 250 mg amoxicillin, and 10 mg omeprazole, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I).
Regarding claims 22 and 32 (misnumbered 31), Depui et al. discloses the antibacterial components formulated in the form of instant release formulations (column 3 lines 48-50), which reads on the claimed recitation of at least 70% of the rifabutin/amoxicillin is released within 60 minutes following oral administration.
Regarding claims 23 and 33 (misnumbered 32), Borody discloses continued treatment for 3-14 days until eradication of the H. pylori infection has been completed (column 5 lines 7-16), which reads on the claimed effective period of time sufficient so as to result in an eradication rate of at least 80%.
Regarding claim 24, Depui et al. discloses that the dosage forms are administered one to several times a day wherein each dosage form preferably comprises 10-80 mg proton pump inhibitor and generally comprises 0.1 mg to 1.2 g antibacterial compound(s) (column 12 line 61 to column 13 line 4) and Borody discloses that typical daily dosages are about 50-2000 mg rifabutin and about 100-5000 mg amoxycillin (column 4 line 62 to column 5 line 1), and thus it would have been prima facie obvious to a person of ordinary skill in the art at the time the inventions was made to follow the suggestions of Depui et al. in view of Borody and Jahagirdar et al. as discussed above and to practice the method of Depui et al. in view of Borody and Jahagirdar et al. as discussed above wherein dosage forms are administered one to several (e.g., 1-3) times a day wherein each dosage form comprises 10-80 mg proton pump inhibitor and 0.1 mg to 1.2 g antibacterial compound(s) and daily dosages are about 50-2000 mg rifabutin and about 100-5000 mg amoxycillin, with a reasonable expectation of success, which overlaps the claimed recitation of 4 capsules three times daily for a total daily oral dose of 150 mg rifabutin, 3000 mg amoxicillin, and 120 mg omeprazole, given that 3 times daily of capsules resulting in 150 mg rifabutin daily requires four capsules of 12.5 mg rifabutin each at each time, and such four capsules three times daily totaling 3000 mg amoxicillin per day results in capsules with 250 mg amoxicillin each, and such four capsules administered three times daily for a total of 120 mg omeprazole require each capsule to have 10 mg omeprazole in each capsule, all of which are within the disclosed ranges.
Regarding claims 25 and 31 (misnumbered 30), Depui et al. discloses that the proton pump inhibitor can be omeprazole such as magnesium omeprazole (column 5 lines 1-10; claims 6-7), which reads on the claimed magnesium omeprazole.
Regarding claim 30 (misnumbered claim 29), Depui et al. discloses that the proton pump inhibitor can be omeprazole (claim 6), which reads on the claimed omeprazole.
Claims 26-28 and 34-37 (misnumbered 33-36) are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Depui et al. in view of Borody and Jahagirdar et al. as applied to claims 21-25 and 29-33 (misnumbered 29-32) above, and further in view of Treiber et al. (Expert Opinion on Pharmacotherapy, 8:3, 2007, pages 329-350) and Miralles et al. (WO 2007/077158 A1; published 12 July 2007).
Depui et al., Borody, and Jahagirdar et al. are relied upon as discussed above.
Depui et al., Borody, and Jahagirdar et al. do not disclose 25-O-desacetylrifabutin as in claims 26-27, 34 (misnumbered 33), and 36 (misnumbered 35), and they do not disclose amoxicillin trihydrate as in claims 27-28 and 35-36 (misnumbered 34-35).
Regarding claims 26-27, 34 (misnumbered 33), and 36 (misnumbered 35), Treiber et al. discloses treatment and dosing of Helicobacter pylori infection (title) wherein 25-O-desacetylrifabutin has an activity equal to the parent drug rifabutin (page 38 last paragraph), reading on the claimed 25-O-desacetylrifabutin.
Regarding claims 26-27, 34 (misnumbered 33), and 36 (misnumbered 35), it would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to substitute the 25-O-desacetylrifabutin of Treiber et al. for the rifabutin in the composition and method of Depui et al. in view of Borody and Jahagirdar et al. as discussed above, with a reasonable expectation of success. A person of ordinary skill in the art at the time the invention was made would have been motivated to do so to successfully treat a helicobacter pylori infection using an H. pylori antibacterial known to have an activity equal to the parent drug rifabutin, and given that it is prima facie obvious to substitute equivalents known for the same purpose per MPEP 2144.06(II).
Regarding claims 27-28 and 34-36 (misnumbered 33-35), Miralles et al. discloses pharmaceutical compositions for the eradication of helicobacter pylori (title) comprising a proton pump inhibitor and amoxicillin (abstract) wherein a preferred amoxicillin compound is amoxicillin trihydrate (page 7 lines 16-18), reading on the claimed amoxicillin trihydrate.
Regarding claims 27-28 and 34-36 (misnumbered 33-35), it would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to combine the teachings of Depui et al., Borody, Jahagirdar et al., and Miralles et al. by making the composition of Depui et al. in view of Borody and Jahagirdar et al. as discussed above using amoxicillin trihydrate as the amoxicillin therein, with a reasonable expectation of success. A person of ordinary skill in the art at the time the invention was made would have been motivated to do so to use a form of amoxicillin therein known to be a preferred form in pharmaceutical compositions for treating H. pylori, because Depui et al. suggests using amoxicillin or a hydrate thereof, and Miralles et al. teaches that amoxicillin trihydrate is a known preferred form in pharmaceutical compositions for treating H. pylori.
Further regarding claim 37 (misnumbered 36), Depui et al. discloses that the dosage forms are administered one to several times a day wherein each dosage form preferably comprises 10-80 mg proton pump inhibitor and generally comprises 0.1 mg to 1.2 g antibacterial compound(s) (column 12 line 61 to column 13 line 4) and Borody discloses that typical daily dosages are about 50-2000 mg rifabutin and about 100-5000 mg amoxycillin (column 4 line 62 to column 5 line 1), and thus it would have been prima facie obvious to a person of ordinary skill in the art at the time the inventions was made to follow the suggestions of Depui et al. in view of Borody and Jahagirdar et al. as discussed above and to practice the method of Depui et al. in view of Borody and Jahagirdar et al. as discussed above wherein dosage forms are administered one to several (e.g., 1-3) times a day wherein each dosage form comprises 10-80 mg proton pump inhibitor and 0.1 mg to 1.2 g antibacterial compound(s) and daily dosages are about 50-2000 mg rifabutin and about 100-5000 mg amoxycillin, with a reasonable expectation of success, which overlaps the claimed recitation of 4 capsules three times daily for a total daily oral dose of 150 mg rifabutin, 3000 mg amoxicillin, and 120 mg omeprazole, given that 3 times daily of capsules resulting in 150 mg rifabutin daily requires four capsules of 12.5 mg rifabutin each at each time, and such four capsules three times daily totaling 3000 mg amoxicillin per day results in capsules with 250 mg amoxicillin each, and such four capsules administered three times daily for a total of 120 mg omeprazole require each capsule to have 10 mg omeprazole in each capsule, all of which are within the disclosed ranges.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL B. PALLAY whose telephone number is (571)270-3473. The examiner can normally be reached on Monday through Friday from 8:30 AM to 5:00 PM Eastern Time.
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/MICHAEL B. PALLAY/Primary Examiner, Art Unit 1617