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 .
DETAILED ACTION
Claims 29-47 are pending in the application. Claims 29-47 are rejected.
Election/Restrictions
Applicant has cancelled subject matter of Group II as set forth in the restriction (subject matter involving compounds of formula (II)). Since Applicant’s amendment only presents claims directed to subject matter involving compounds of formula (I) and does not traverse the restriction, the Examiner considers the amendment to be an election by original presentation of subject matter involving compounds of formula (I).
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statement(s) filed on April 7th, 2026, February 24th, 2026, October 24th, 2025, August 29th, 2025, November 12th, 2024 and April 24th, 2024.
Comment on Patent Family
Regarding prior art rejections presented below, Applicant in, for instance, parent application No. 14/829,180, filed a declaration to address a prior art reference. While rejections over the same reference could be overcome analogously to the parent application, Applicant is directed to MPEP 201.06(c)(IX):
Affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132 filed during the prosecution of the prior nonprovisional application do not automatically become a part of a continuation or divisional application filed under 37 CFR 1.53(b). Where it is desired to rely on an earlier filed affidavit or declaration, the applicant should make such remarks of record in the 37 CFR 1.53(b) application and include a copy of the original affidavit or declaration filed in the prior nonprovisional application.
If Applicant wishes to take the same approach, a declaration should be filed in the instant application.
Claim Rejections - 35 USC § 112(b)
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 33-35 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.
Each of claims 33-35 refers to a chemical formula in brackets that is not defined within the instant claims. It is unclear if the formula is superfluous or if Applicant is attempting to recite some additional limitation within a formula that is not presently defined.
Claim Rejections - 35 USC § 103
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.
(1 of 4) Claims 29-32, 35-37 and 43-47 is/are rejected under 35 U.S.C. 103 as being unpatentable over International Application Publication No. WO 0057701 A1 by Zhao et al. in view of Corris et al. Eur. Repsir. Rev. 2014, 23, 488-497.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Zhao et al. teach (title) “prostaglandin compounds, compositions and methods of treating peripheral vascular disease and pulmonary hypertension.” Furthermore, the prior art teaches on page 10 (descriptions of figures 1-5) that various tests were performed on decreasing “pulmonary arterial pressure” where instant claim 29 recites the treatment of “pulmonary arterial hypertension.” The prior art teaches the pulmonary artery is the target areas as follows on page 12:
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As compounds for use in the methods above, the prior art teaches conjugation of compounds to increase the effective life of the compound (page 11, line 15 through page 12, line 1). As particular structures, the prior art teaches the following on page 15:
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The prior art further teaches the following embodiment on page 16:
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Regarding the preparation of particular compounds, Zhao et al. teach the following structure on page 30 as compound X:
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The prior art structure has the same backbone as instantly claimed except for the presence of groups corresponding to R1 and/or R2. In example 3 on pages 33 and 34, the prior art teaches the synthesis of an ester where the final compound contains a free carboxylic acid and the alcohol groups are esterified as follows:
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The structure where the two hydroxy groups are replaced with –OC(=O)CH2CH2O-mPEG groups would at least be embraced by the first options listed for R1 and R2 where R3 is a substituted C1 or C2 alkyl group. The second and fourth options also embrace this type of structure where R4 and R5 are hydrogen, m is 2 and R6 is R3 where R3 is a substituted C1 or C2 alkyl group. The prior art structure meets the formula (I) limitations of instant claims 29, 35, 36 and 37.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art teaches methods of treating conditions instantly claimed and further teaches an example of a compound that possesses the same backbone instantly claimed (where the instant claims embrace administration of stereoisomers) but does not teach administration with an endothelin receptor antagonist and/or a PDE5 inhibitor. Additional limitations and dependent claims are addressed below.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Regarding the treatment of pulmonary arterial hypertension, Corris et al. teach on page 489: “Other recommended treatments in functional class IV PAH include ambrisentan, bosentan, macitentan, riociguat, sildenafil, tadalafil and the thermostable prostacyclin analogues treprostinil (subcutaneous, intravenous and inhaled) and iloprost (inhaled and intravenous).” Instant claim 31 recites ambrisentan and bosentan and instant claim 32 recites sildenafil and tadalafil. Ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. It would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to combine the two compounds known in the prior art which are taught to be useful for the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Thus, the skilled artisan would reasonably expect success in this combination.
Regarding instant claims 43-47, Zhao et al. teach the following on page 25:
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Accordingly, Zhao et al. teach that the compounds may be administered topically (claim 46), orally (claim 43), parenterally (claim 44), by inhalation (claim 47), subcutaneously and intravenously (claim 45). In the interest of determining which particular mode of administration would provide the optimum results, a person having ordinary skill in the art would have been motivated to test the approaches taught by Zhao et al.
(2 of 4) Claims 29-34, 37-40, 46 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over International Application No. WO 2014110491 A1 by Becker et al. in view of U.S. Patent PGPub No. 2005/0085540 A1 by Phares et al. and in further view of Corris et al. Eur. Repsir. Rev. 2014, 23, 488-497.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Becker et al. teach compounds of the following general formula (page 2):
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Furthermore, Becker et al. point to the following sub-generic embodiment on pages 34 and 35:
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where on page 35 the prior art points to the use of –OH, -OR11 or P1.
As an example, Becker et al. teach the following compound on page 45:
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The compound above differs from an instant compound (where R2 is H and R1 is C(O)R3 where R3 is cyclopropyl, meeting the structural limitations of instant claims 29, 33, 38 and 39) based on the presence of a methyl ester instead of a free carboxylic acid. As a further example, Becker et al. teach the following compound on page 52:
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The compound above differs from an instant compound (where R1 is H and R2 is C(O)R3 where R3 is cyclopentyl, meeting the structural limitations of instant claims 29, 34, 38 and 40) based on the presence of a methyl ester instead of a free carboxylic acid. As a further example, Becker et al. teach the following compound on page 53:
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The compound above differs from an instant compound (where R1 is H and R2 is C(O)R3 where R3 is cyclopropyl, meeting the structural limitations of instant claims 29, 34, 38 and 40) based on the presence of a methyl ester instead of a free carboxylic acid. As a further example, Becker et al. teach the following compound on page 53:
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The compound differs from an instant compound (where R1 is H and R2 is C(O)R3 where R3 is C4 alkyl, meeting the structural limitations of instant claims 29, 34, 37, 38 and 40) based on the presence of a methyl ester instead of a free carboxylic acid. Regarding each structure above, the instant claims encompass stereoisomers thereof.
Regarding the utility of the compounds of the prior art, Becker et al. teach that the compounds are useful in the treatment of “pulmonary hypertensions (PH) or pulmonary arterial hypertension (PAH)” in the abstract.
Regarding the intended applications of instant claim 29, Becker et al. teach that treprostinil is useful as follows (page 17):
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Becker et al. further teach application in combinations as follows on the same page:
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Regarding instant claims 46 and 47, Becker et al. teach transdermal administration on page 113 as claims 66-68.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The instant claims encompass methods of using combinations generally taught in the prior art comprising a compound having the same structures as depicted above where the methyl ester is a carboxylic acid.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Prior to the disclosure of Becker et al. the use of both the free acid and alkyl esters were known for prostacyclic compounds. For instance, Phares et al. teach methods of treating hypertension using compounds of the following general formula:
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Furthermore, Phares et al. point to the use of a methyl group in paragraph [0020] as follows:
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Accordingly, both Becker et al. and Phares et al. teach the use of free carboxylic acids as well as alkyl esters including methyl esters. “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” In re Deuel 34 USPQ2d 1210 at 1214. Furthermore MPEP 2144.09 (II) states: “Compounds which are […] homologs (…) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).” While the difference is a hydrogen group versus a methyl group on a carboxylic acid, which is a different situation compared to, for instance, hydrogen versus methyl on a phenyl ring, the CCPA considered an analogous situation where the difference was between a carboxylic acid and an ethyl ester; however, the court affirmed an obviousness rejection and noted the following on page 409:
Having considered, on the one hand, the very close structural similarities of the claimed compounds and the reference compounds, the utility disclosures of the references, and the suggestion of polychlorination in the French patent, and, on the other hand, the apparent unobviousness of the utility of the claimed compounds as herbicides, we find that a prima facie case of obviousness has been made out by the examiner.
Analogously, the disclosure of Becker et al. teaches a compound that differs based a methyl ester versus the free acid and points to the use of an –OH group. Furthermore, the compounds disclosed by Becker et al. and Phares et al. have the same utility, i.e. for treating hypertension. For this reason, a person having ordinary skill in the art would have been motivated to prepare the instantly claimed compounds discussed above with the reasonable expectation they that would be useful in the same utilities and have similar properties to compound of Becker et al.
It is further noted that the title and abstract of Becker et al. points to the compounds as “prodrugs of treprostinil,” which has the following structure:
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Compounds of the prior art contain modifications of treprostinil where the carboxylic acid is converted to an ester and where one of the hydroxyl groups is converted to an ester. In the interest of determining the effect of the different modifications, a person having ordinary skill in the art would have been motivated to prepare the instantly claimed compound discussed above in order to test the effect of only having the hydroxyl groups substituted.
Regarding the treatment of pulmonary arterial hypertension in combination, Corris et al. teach on page 489: “Other recommended treatments in functional class IV PAH include ambrisentan, bosentan, macitentan, riociguat, sildenafil, tadalafil and the thermostable prostacyclin analogues treprostinil (subcutaneous, intravenous and inhaled) and iloprost (inhaled and intravenous).” Instant claim 31 recites ambrisentan and bosentan and instant claim 32 recites sildenafil and tadalafil. Ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. It would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to combine the two compounds known in the prior art which are taught to be useful for the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Thus, the skilled artisan would reasonably expect success in this combination.
(3 of 4) Claims 43-45 are rejected under 35 U.S.C. 103 as being unpatentable over International Application No. WO 2014110491 A1 by Becker et al. in view of U.S. Patent PGPub No. 2005/0085540 A1 by Phares et al. and in further view of Corris et al. Eur. Repsir. Rev. 2014, 23, 488-497, as applied to claims 29-34, 37-40, 46 and 47 above, and in further view of U.S. Patent PGPub No. 2005/0165111 A1 by Wade et al.
The prior art discussed above renders obvious the method of claim 29; however, Becker et al., Phares et al. and Corris et al. do not teach each method of administration of instant claims 43-45. Wade et al., however, teach that treprostinil and its derivations can be administered according to the routes instantly claimed as follows on page 3:
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Accordingly, a person having ordinary skill in the art in seeking to apply the instantly claimed compositions to situations where the structurally analogous treprostinil is useful would have been motivated to test the routes of administration noted above.
(4 of 4) Claims 29-34, 37-40 and 42-47 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent PGPub No. 2015/0166503 by Becker et al. in view of U.S. Patent PGPub No. 2005/0085540 A1 by Phares et al.
The applied reference (Becker et al.) has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Becker et al. teach compounds of the following general formula (page 1):
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Furthermore, Becker et al. point to the following sub-generic embodiment on page 15:
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where on page 15 the prior art points to the use of –OH, -OR11 or P1. As a particular example, Becker et al. teach the following compound on page 19:
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The compound above differs from an instant compound or its stereoisomer (where R2 is H and R1 is C(O)R3 where R3 is C4 alkyl, meeting the structural limitations of instant claims 29, 33, 37, 38, 39 and 42 relative to compound Ia-4) based on the presence of a methyl ester instead of a free carboxylic acid. As an additional example, Becker et al. teach the following compound on page 23:
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The compound above differs from an instant compound or its stereoisomer (where R1 is H and R3 is C(O)R3 where R3 is cyclopropyl, meeting the structural limitations of instant claims 29, 34, 38 and 40) based on the presence of a methyl ester instead of a free carboxylic acid. As an additional example, the prior art teaches the following compound on page 19:
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The compound above differs from an instant compound or its stereoisomer (where R2 is H and R1 is C(O)R3 where R3 is C4 alkyl, meeting the structural limitations of instant claims 29, 33, 37, 38, 39 and 42 relative to compound Ia-3) based on the presence of a methyl ester instead of a free carboxylic acid.
Regarding the utility of the compounds of the prior art, Becker et al. teach that the compounds are useful in the treatment of “pulmonary hypertensions (PH) or pulmonary arterial hypertension (PAH)” in the abstract, where the instant claim 29 is directed to treating PAH.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The instant claim 29 encompasses methods of treating the condition of the prior art with compounds having the same structure as discussed above where the methyl ester is a carboxylic acid. Furthermore, the instant claims require administration of a combination with an endothelin receptor antagonist and/or PDE5 inhibitor.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Prior to the disclosure of Becker et al. the use of both the free acid and alkyl esters were known for prostacyclic compounds. For instance, Phares et al. teach methods of treating hypertension using compounds of the following general formula:
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Furthermore, Phares et al. point to the use of a methyl group in paragraph [0020] as follows:
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Accordingly, both Becker et al. as well as Phares et al. teach the use of free carboxylic acids as well as alkyl esters including methyl esters. “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” In re Deuel 34 USPQ2d 1210 at 1214. Furthermore MPEP 2144.09 (II) states: “Compounds which are […] homologs (…) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).” While the difference is a hydrogen group versus a methyl group on a carboxylic acid, which is a different situation compared to, for instance, hydrogen versus methyl on a phenyl ring, it is noted that the CCPA considered an analogous situation where the difference was between a carboxylic acid and an ethyl ester; however, the court affirmed an obviousness rejection and noted the following on page 409:
Having considered, on the one hand, the very close structural similarities of the claimed compounds and the reference compounds, the utility disclosures of the references, and the suggestion of polychlorination in the French patent, and, on the other hand, the apparent unobviousness of the utility of the claimed compounds as herbicides, we find that a prima facie case of obviousness has been made out by the examiner.
Analogously, the disclosure of Becker et al. teaches a compound that differs based a methyl ester versus the free acid and points to the use of an –OH group. Furthermore, the compounds disclosed by Becker et al. and Phares et al. have the same utility, i.e. for treating hypertension. For this reason, a person having ordinary skill in the art would have been motivated to prepare the instantly claimed compounds discussed above with the reasonable expectation they that would be useful in the same utilities and have similar properties to compound of Becker et al.
It is further noted that the title and abstract of Becker et al. points to the compounds as “prodrugs of treprostinil,” which has the following structure:
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The compounds 22, 23 and 48 of the prior art as discussed above both contain modifications of treprostinil where the carboxylic acid is converted to an ester and where one of the hydroxyl groups is converted to an ester. In the interest of determining the effect of the different modifications, a person having ordinary skill in the art would have been motivated to prepare the instantly claimed compounds discussed above in order to test the effect of only having the hydroxyl groups substituted. For these reasons, the claimed methods of using compounds that differ from the prior art compounds based on a methyl ester versus a free acid would have been suggested to a person having ordinary skill in the art.
Regarding the instantly recited combination approach, Becker et al. teach combinations to treat PAH on page 40 (paragraph [0232]) including with ambrisentan, bosentan and Actelion-1 in paragraph [0234] (recited in instant claim 31) and sildenafil and tadalfil (recited in instant claim 32). Ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. It would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to combine the two compounds known in the prior art which are taught to be useful for the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Thus, the skilled artisan would reasonably expect success in this combination.
Regarding instant claims 43-47, Becker et al. teach the additional instantly claimed administration methods on page 36 as part of paragraph [0180].
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
(1 of 16) Claims 29-34, 36-40 and 42-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,643,911 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of treating pulmonary arterial hypertension (claim 7 of the patent) using compounds embraced by instant formula (I). For instance, compound Ia-1 of claim 4 of the patent is embraced by instant claims 29, 33, 37, 38, 39 and 42. Regarding additional claims not previously cited, Compound Ia-6 of the patent is embraced by instant claim 36. Regarding additional claims not previously cited, Compound Ib-1 of the patent is embraced by instant claims 34 and 40. The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 43-47, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(2 of 16) Claims 29-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 9,957,220 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of treating pulmonary arterial hypertension (claim 21 of the patent) using compounds embraced by instant formula (I). For instance, claim 30 of the patent recites definitions of R1 and R2 embraced by instant claims 29, 36, 37, 38 and that correspond to permutations of instant claim 42. Regarding instant claims 33-35 and 39-41, claims 15-18 of the patent recite analogous limitations. The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 43-47, claims 22-26 of the patent recite analogous modes of administration.
(3 of 16) Claims 29-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,464,877 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of treating pulmonary arterial hypertension (claim 11 of the patent) using compounds embraced by instant formula (I). For instance, claim 4 of the patent recites definitions of R1 and R2 embraced by instant claims 29, 37, 38 and that correspond to permutations of instant claim 42. Claim 2 of the patent recites analogous definitions to instant claim 36. Regarding instant claims 33-35 and 39-41, claims 5-8 of the patent recite analogous limitations. The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 43-47, claims 12-17 of the patent recite analogous modes of administration.
(4 of 16) Claims 29-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,703,706 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of treating pulmonary arterial hypertension (claim 15 of the patent) using compounds embraced by instant formula (I). For instance, claim 17 of the patent recites definitions of R1 and R2 embraced by instant claims 29, 36, 37, 38 and that correspond to various permutations of instant claim 42. Regarding instant claims 33-35 and 39-41, claims 4-6 of the patent recite analogous limitations. The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 43-47, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(5 of 16) Claims 29-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,988,435 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of accomplishing certain intended effects using compounds embraced by instant formula (I). For instance, claim 3 of the patent recites definitions of R1 and R2 embraced by instant claims 29, 36, 37, 38 and that correspond to various permutations of instant claim 42. Regarding instant claims 33-35 and 39-41, claims 4-6 of the patent recite analogous limitations. The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The preamble of the claims of the patent only appear to recite intended effects or otherwise inherent properties of the compounds being administrated. Regarding instant claims 43-47, claims 7-11 of the patent recite analogous modes of administration.
(6 of 16) Claims 29-42, 46 and 47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,034,645 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite transdermal patches containing compounds embraced by instant formula (I). For instance, compound Ia-1 of claim 17 of the patent is embraced by instant claims 29, 33, 37, 38, 39 and 42. Regarding additional claims not previously cited, Compound Ia-6 of the patent is embraced by instant claim 36. Regarding additional claims not previously cited, Compound Ib-1 of the patent is embraced by instant claims 34 and 40. Regarding instant claims 35 and 41, claim 16 of the patent recites an analogous embodiment. The instant method requires treatment of pulmonary arterial hypertension and the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular for pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 46 and 47, the claims of the patent are directed to transdermal products.
(7 of 16) Claims 29-34, 36-40 and 42-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,802,105 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of treating pulmonary arterial hypertension (claim 10 of the patent) using compounds embraced by instant formula (I). For instance, compound Ia-22 of claim 1 of the patent is embraced by instant claims 29, 33, 37, 38 and 39. Regarding additional claims not previously cited, Compound Ia-24 of the patent is embraced by instant claim 36. Regarding additional claims not previously cited, Compound Ib-22 of the patent is embraced by instant claims 34 and 40. Regarding instant claim 42, the instant claims encompass structural homologs, such as instant compound Ia-1 that differs from compound Ia-22 of the patent based on replacement of methyl with hydrogen. “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its
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often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” In re Deuel 34 USPQ2d 1210 at 1214. Furthermore MPEP 2144.09 (II) states: “Compounds which are […] homologs (…) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).”
The issue of patentability over the replacement of alkyl groups for hydrogen has arisen many times. For instance, the replacement of a methylene group with a dialkyl-substituted methylene group was determined to be prima facie obvious on the ground that “one skilled in the art would have been, prima facie, motivated to make the claimed compounds in the expectation that they, too, would possess antimicrobial activity." (In re Wood 199 USPQ 137) See also In re Doebel 174 USPQ 158 (where replacement of methyl for hydrogen on an amino nitrogen was considered prima facie obvious – at page 159); In re Druey 138 USPQ 39 (where replacement of methyl for hydrogen on a known compound was considered prima face obvious based on the homologous and close structural relationship to the known compound – at page 41); In re Lohr 137 USPQ 548 (where the replacement of a methyl group for a hydrogen on two positions of a tetrahydropyran ring on a known compound was not considered a patentable modification given the close structural relationship to the known compounds - at page 550); Ex parte Bluestone 135 USPQ 199 (where fungicidal compounds differing by hydrogen versus methyl on the nitrogen of a thiazolidine-2-thione ring were considered homologs and were not found to be patentable over each other without a showing of unexpected results – at page 200); Ex parte Weston 121 USPQ 429 (where the replacement of methyl for hydrogen on the nitrogen of a piperazine ring was not found to be a patentable modification); Ex parte Fauque 121 USPQ 425 (where di(methyl-furyl)-methane was considered a higher homolog of difuryl-methane and unpatentable without a showing of unexpected results - at page 426). In the instant case, a person having ordinary skill in the art at the time the invention was made would have been motivated to synthesize and apply the instantly claimed homologs with the reasonable expectation that they would have the same utility as the closest structurally related compounds recited in the patent and with the motivation of obtaining additional useful embodiments.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 43-47, claims 11-15 of the patent recite analogous modes of administration.
(8 of 16) Claims 29-34, 36-40 and 42-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,643,847. The claims of the patent recite methods of treating pulmonary arterial hypertension (claim 7 of the patent) using compounds embraced by instant formula (I). For instance, compound Ia-22 of claim 7 of the patent is embraced by instant claims 29, 33, 37, 38 and 39. Regarding additional claims not previously cited, Compound Ia-24 of the patent is embraced by instant claim 36. Regarding additional claims not previously cited, Compound Ib-22 of the patent is embraced by instant claims 34 and 40. Regarding instant claim 42, the instant claims encompass structural homologs, such as instant compound Ia-1 that differs from compound Ia-22 of the patent based on replacement of methyl with hydrogen. “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its
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often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” In re Deuel 34 USPQ2d 1210 at 1214. Furthermore MPEP 2144.09 (II) states: “Compounds which are […] homologs (…) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).”
The issue of patentability over the replacement of alkyl groups for hydrogen has arisen many times. For instance, the replacement of a methylene group with a dialkyl-substituted methylene group was determined to be prima facie obvious on the ground that “one skilled in the art would have been, prima facie, motivated to make the claimed compounds in the expectation that they, too, would possess antimicrobial activity." (In re Wood 199 USPQ 137) See also In re Doebel 174 USPQ 158 (where replacement of methyl for hydrogen on an amino nitrogen was considered prima facie obvious – at page 159); In re Druey 138 USPQ 39 (where replacement of methyl for hydrogen on a known compound was considered prima face obvious based on the homologous and close structural relationship to the known compound – at page 41); In re Lohr 137 USPQ 548 (where the replacement of a methyl group for a hydrogen on two positions of a tetrahydropyran ring on a known compound was not considered a patentable modification given the close structural relationship to the known compounds - at page 550); Ex parte Bluestone 135 USPQ 199 (where fungicidal compounds differing by hydrogen versus methyl on the nitrogen of a thiazolidine-2-thione ring were considered homologs and were not found to be patentable over each other without a showing of unexpected results – at page 200); Ex parte Weston 121 USPQ 429 (where the replacement of methyl for hydrogen on the nitrogen of a piperazine ring was not found to be a patentable modification); Ex parte Fauque 121 USPQ 425 (where di(methyl-furyl)-methane was considered a higher homolog of difuryl-methane and unpatentable without a showing of unexpected results - at page 426). In the instant case, a person having ordinary skill in the art at the time the invention was made would have been motivated to synthesize and apply the instantly claimed homologs with the reasonable expectation that they would have the same utility as the closest structurally related compounds recited in the patent and with the motivation of obtaining additional useful embodiments.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor, which embodiments are disclosed claims 7-10 of the patent (corresponding to instant claims 30-32). Regarding instant claims 43-47, claims 11-15 of the patent recite analogous modes of administration.
(9 of 16) Claims 29-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,394,227 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite compounds embraced by instant formula (I). For instance, compound Ia-1 of claim 11 of the patent is embraced by instant claims 29, 33, 37, 38, 39 and 42. Regarding additional claims not previously cited, Compound Ia-6 of the patent is embraced by instant claim 36. Regarding additional claims not previously cited, Compound Ib-1 of the patent is embraced by instant claims 34 and 40. Regarding instant claims 35 and 41, claim 10 of the patent recites an analogous embodiment. The instant method requires treatment of pulmonary arterial hypertension and the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular for pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Regarding instant claims 46 and 47, claims 20 and 21 of the patent are directed to transdermal products. Regarding instant claims 43-45, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(10 of 16) Claims 29-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,407,707 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent recite methods of accomplishing certain intended effects using compounds embraced by instant formula (I). For instance, compound Ia-1 of claim 8 of the patent is embraced by instant claims 29, 33, 37, 38, 39 and 42. Regarding additional claims not previously cited, Compound Ia-6 of the patent is embraced by instant claim 36. Regarding additional claims not previously cited, Compound Ib-1 of the patent is embraced by instant claims 34 and 40. Regarding instant claims 35 and 41, claim 7 of the patent recites an analogous embodiment. The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The preamble of the claims of the patent only appear to recite intended effects or otherwise inherent properties of the compounds being administrated. Regarding instant claims 43-47, claims 9-14 of the patent recite analogous modes of administration.
(11 of 16) Claims 29-35, 37 and 43-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,371,264 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent are generic to compounds instantly claimed and claim 6 of the patent recites a method of treating pulmonary hypertension and claim 7 of the patent particularly recites pulmonary arterial hypertension. Regarding the scope of the instant compounds, claim 1 of the patent embraces the following structure:
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Claim 1 of the patent recites that Z can be three options where one is –OH, which would overlap with the instant formula (I). Furthermore, claim 1 of the patent further recites that R1 and R2 can be H or P2 where at least one of R1 and R2 is P2. Claim 1 of the patent further defines P2 as including several options that would overlap with the instant claims such as –C(=O)R14 and –C(=O)OR14 where R14 is defined as including cycloalkyl, alkylcycloalkyl, haloalkyl, aryl, heteroaryl, arylalkyl, etc. that would either read explicitly on a definition of the instant variable R3 or where R3 can be considered substituted alkyl. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (1964). Regarding instant claim 37, this claim would still appear to encompass substituted alkyl groups as R3 which would overlap with alkylcycloalkyl, haloalkyl, etc. in the claims of the patent. Regarding instant claims 33-35, the claims of the patent teach that at least one of R1 and R2 is P2 such that embodiments where one is P2 but the other is not (and would be hydrogen) would be two of the three possibilities falling with the scope of the patent claims and embodiments where both P2 would be the third.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding instant claims 46 and 47, claim 8 of the patent recites transdermal administration. Regarding instant claims 43-45, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(12 of 16) Claims 29-35, 37 and 43-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,776,982 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent are generic to compounds instantly claimed and claim 17 of the patent recites a method of treating pulmonary hypertension and claim 18 of the patent particularly recites pulmonary arterial hypertension. Regarding the scope of the instant compounds, claim 12 of the patent embraces the following structure:
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Claim 12 of the patent recites that Z can be three options where one is –OH, which would overlap with the instant formula (I). Furthermore, claim 12 of the patent further recites that R1 and R2 can be H or P2 where at least one of R1 and R2 is P2. Claim 12 of the patent further defines P2 as including several options that would overlap with the instant claims such as –C(=O)R14 and –C(=O)OR14 where R14 is defined as including cycloalkyl, alkylcycloalkyl, haloalkyl, aryl, heteroaryl, arylalkyl, etc. that would either read explicitly on a definition of the instant variable R3 or where R3 can be considered substituted alkyl. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (1964). Regarding instant claim 37, this claim would still appear to encompass substituted alkyl groups as R3 which would overlap with alkylcycloalkyl, haloalkyl, etc. in the claims of the patent. Regarding instant claims 33-35, the claims of the patent teach that at least one of R1 and R2 is P2 such that embodiments where one is P2 but the other is not (and would be hydrogen) would be two of the three possibilities falling with the scope of the patent claims and embodiments where both P2 would be the third.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding instant claims 46 and 47, claim 19 of the patent recites transdermal administration. Regarding instant claims 43-45, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(13 of 16) Claims 29-35, 37 and 43-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,752,605 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent are generic to compounds instantly claimed and claim 17 of the patent recites a method of treating pulmonary arterial hypertension. Regarding the scope of the instant compounds, claim 11 of the patent embraces the following structure:
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Claim 11 of the patent recites that Z can be three options where one is –OH, which would overlap with the instant formula (I). Furthermore, claim 11 of the patent further recites that R1 and R2 can be H or P2 where at least one of R1 and R2 is P2. Claim 12 of the patent further defines P2 as including several options that would overlap with the instant claims such as –C(=O)OR14 where R14 is defined as alkyl that would read explicitly on the definition of the instant variable R3 as further overlapping with instant claim 37. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (1964). Regarding instant claims 33-35, the claims of the patent teach that at least one of R1 and R2 is P2 such that embodiments where one is P2 but the other is not (and would be hydrogen) would be two of the three possibilities falling with the scope of the patent claims and embodiments where both P2 would be the third.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding instant claims 46 and 47, claim 18 of the patent recites transdermal administration. Regarding instant claims 43-45, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(14 of 16) Claims 29-35, 37 and 43-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,339,139 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent are generic to compounds instantly claimed and claim 17 of the patent recites a method of treating pulmonary arterial hypertension. Regarding the scope of the instant compounds, claim 11 of the patent embraces the following structure:
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Claim 11 of the patent recites that Z can be three options where one is –OH, which would overlap with the instant formula (I). Furthermore, claim 11 of the patent further recites that R1 and R2 can be H or P2 where at least one of R1 and R2 is P2. Claim 12 of the patent further defines P2 as including several options that would overlap with the instant claims such as –C(=O)R14 where R14 is defined as alkyl that would read explicitly on the definition of the instant variable R3 as further overlapping with instant claim 37. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (1964). Regarding instant claims 33-35, the claims of the patent teach that at least one of R1 and R2 is P2 such that embodiments where one is P2 but the other is not (and would be hydrogen) would be two of the three possibilities falling with the scope of the patent claims and embodiments where both P2 would be the third.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding instant claims 46 and 47, claim 18 of the patent recites transdermal administration. Regarding instant claims 43-45, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(15 of 16) Claims 29-35, 37 and 43-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,046,666 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent are generic to compounds instantly recited and claim 15 of the patent particularly recites treating pulmonary arterial hypertension. Regarding the scope of the instant compounds, claim 1 of the patent embraces the following structure:
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Claim 1 of the patent recites that Z can be five options where one is –OH, which would overlap with the instant formula (I). Furthermore, claim 1 of the patent further recites that R1 and R2 can be H or P2 where at least one of R1 and R2 is P2. Claim 1 of the patent further defines P2 as including options that would overlap with the instant claimed option of –C(=O)OR3 where R3 can be considered substituted alkyl. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (1964). Regarding instant claim 37, this claim would still appear to encompass substituted alkyl groups as R3 which would overlap with the claims of the patent. Regarding instant claims 33-35, the claims of the patent teach that at least one of R1 and R2 is P2 such that embodiments where one is P2 but the other is not (and would be hydrogen) would be two of the three possibilities falling with the scope of the patent claims and embodiments where both P2 would be the third.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding instant claims 43, 46 and 47, claim 17 of the patent recites oral and transdermal administration. Regarding instant claims 44 and 45, the claims of the patent do not teach each mode of administration; however, Harbeson teaches oral, parenteral, subcutaneous, intravenous, topical, transdermal application in paragraph [0081] (page 8). A person having ordinary skill in the art would have at least been motivated to test modes of administration that have been disclosed for analogous compositions.
(16 of 16) Claims 29-35, 37, 46 and 47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,505,535 in view of U.S. Patent PGPub No. 2011/0294815 A1 by Harbeson. The claims of the patent are drawn to transdermal patches comprising a structure generic to compounds instantly claimed where claim 20 of the patent particularly recites treating pulmonary arterial hypertension. Regarding the scope of the instant compounds, claim 6 of the patent embraces the following structure:
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Claim 6 of the patent recites that Z can be three options where one is –OH, which would overlap with the instant formula (I). Furthermore, claim 6 of the patent further recites that R1 and R2 can be H or P2 where at least one of R1 and R2 is P2. Claim 6 of the patent further defines P2 as including several options that would overlap with the instant claims such as –C(=O)R14 and –C(=O)OR14 where R14 is defined as including alkyl, cycloalkyl, alkylcycloalkyl, haloalkyl, aryl, heteroaryl, arylalkyl, etc. that would either read explicitly on a definition of the instant variable R3 or where R3 can be considered substituted alkyl. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (1964). Regarding instant claim 37, this claim would still appear to encompass substituted alkyl groups as R3 which would overlap with alkylcycloalkyl, haloalkyl, etc. in the claims of the patent. Regarding instant claims 33-35, the claims of the patent teach that at least one of R1 and R2 is P2 such that embodiments where one is P2 but the other is not (and would be hydrogen) would be two of the three possibilities falling with the scope of the patent claims and embodiments where both P2 would be the third.
The instant method requires the further administration of an endothelin receptor antagonist and/or PDE5 inhibitor. A person having ordinary skill in the art, however, in viewing the treprostinil backbone structure of the compounds of the patent would have expected such combinations to be useful and in particular to be useful in the treatment of patients having pulmonary arterial hypertension. For instance, Harbeson teaches analogues of treprostinil (abstract), teaches in paragraph [0003] that treprostinil is useful in treating pulmonary arterial hypertension and further teaches combinations for treating pulmonary arterial hypertension in paragraph [0100] on page 10 including with sildenafil, bosentan, and ambrisentan, which are recited in instant claims 31 and 32 and where ambrisentan is an antagonist of ETA and bosentan is an antagonist of ETA and ETB, as embraced by instant claim 30. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding instant claims 46 and 47, the claims of the patent are drawn to transdermal products.
Conclusion
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
