FINAL DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Receipt is acknowledged of the claim amendments filed on 10 December 2025.
Claims 1-225, 227-228, 231, 233-234, 243-244, 248, 251-253, 257-259, 261 and 263-264 are cancelled.
Consequently, claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are presented for examination herein.
Information Disclosure Statement
The information disclosure statement (IDS) filed 12/10/2025 has been considered by the Examiner. A signed and initialed copy of the IDS is included with the instant Office Action.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. Claim 226 contains the transitional language “comprising” for the “dry powder composition”. The transitional term “comprising”, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Claim 226 also recites that the dry powder composition comprises amounts of (i), (ii) and (iii), “wherein the entirety of (i), (ii) and (iii) is 100 wt%”, which is interpreted that the 100 wt% is in reference to the combined wt% of (i), (ii) and (iii) and not the total weight of the dry powder composition. In light of this broadest reasonable interpretation, the “dry powder composition” does not exclude additional, unrecited elements.
Rejections Withdrawn
The rejection of claims 226, 229-230, 232, 235-242, 245, 254-260, 262 and 264 under 35 U.S.C. 103(a) as being unpatentable over MALININ (US 9,255,064; cited in IDS filed 12/04/2023; patent date of 09 February 2016) in view of ARMER (US 2017/0304276 A1, publication date of 26 October 2017) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018), is withdrawn in view of the claim amendments filed 10 December 2025.
The rejection of claims 246-247 and 249-250 under 35 U.S.C. 103(a) as being unpatentable over MALININ (US 9,255,064; cited in IDS filed 12/04/2023; patent date of 09 February 2016) in view of ARMER (US 2017/0304276 A1, publication date of 26 October 2017) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018) as applied to claims 226, 229-230, 232, 235-242, 245, 254-260, 262 and 264, and further in view of THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics), is withdrawn in view of the claim amendments filed 10 December 2025.
All the rejections of claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-260, 262 and 264 on the ground of nonstatutory double patenting as being unpatentable over patents and reference applications as set forth in the office action mailed 10 June 2025 are withdrawn in view of the claim amendments filed 10 December 2025.
New Grounds of Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 260 and 262 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 260, which depends directly on claim 226, recites “wherein the compound is formulated in a dry powder composition further comprising mannitol” while claim 226 recites a dry powder composition that already comprises mannitol. Claim 262 which is dependent on claim 260 is also rejected for not remedying the deficiency. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over MALININ (US 9,255,064; cited in IDS filed 12/04/2023; patent date of 09 February 2016) in view of PAN (CN 1593414 A, date published: 16 March 2005) and THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics).
Malinin is primarily directed towards prostacyclin compounds, compositions comprising the same, and methods for treating including pulmonary hypertension (abstract).
Regarding claims 226, 229, 245 and 255-256, Malinin discloses a method for treating pulmonary hypertension (PH) (column 7, lines 10-11) that includes pulmonary administration of a composition comprising the prostacyclin compound that is administered once daily to the patient via including a dry powder inhaler (column 7, lines 24-28). Malinin discloses treprostinil alkyl esters Formula (A):
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wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl) (column 51, lines 55-58; column 52, Formula (A); column 53, compound C16-TR). Malinin discloses inhaled C16-TR (e.g., R1 is hexadecyl) at a dose of 0.6-18 µg/kg (e.g. dose for 70 kg person is 42 µg-1,260 µg) was well tolerated with no evidence of body weight and organ weight change after dosing for 14 consecutive days (column 82, lines 49-51).
Regarding claims 230 and 232, Malinin discloses a method for treating pulmonary hypertension (PH) (column 7, lines 10-11). Malinin discloses that pulmonary hypertension has been classified into five groups by the WHO (e.g., includes class I and class III (e.g., group 1 PH and group 3 PH, respectively)) (column 1, lines 29-48).
Regarding claim 235-236, Malinin discloses that group I is called pulmonary arterial hypertension (PAH) (column 1, lines 30-31).
Regarding claim 237-238, Malinin discloses that group III pulmonary hypertension is characterized as PH associated with lung diseases including interstitial lung diseases (column 1, lines 38-40).
Regarding claim 239, Malinin discloses pulmonary hypertension caused by systemic disorders including sarcoidosis (column 1, lines 44-47).
Regarding claims 240-242, Malinin discloses that the therapeutic response of the patient is including improved exercise capacity (e.g., as measured by the six-minute walk test) compared to pretreatment (column 42, lines 24-32).
Regarding claim 254, Malinin discloses that the pulmonary delivery devices include a capsule-based dry powder inhaler (paragraph bridging columns 48 and 49).
Regarding claim 255, Malinin discloses that each administration (e.g., single dosing session) comprises 1 to 5 doses (puffs (e.g., inhalations)) from a DPI (column 43, lines 9-10).
Malinin does not specifically teach dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. Malinin does not specifically teach titrating an initial dose to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan and Therapeutics.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Regarding claims 249-250, Malinin discloses inhaled C16-TR (e.g., R1 is hexadecyl) at a dose of 0.6-18 µg/kg (e.g. dose for 70 kg person is 42 µg-1,260 µg) was well tolerated with no evidence of body weight and organ weight change after dosing for 14 consecutive days (column 82, lines 49-51).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering once daily a dose of a dry powder enclosed in a capsule that comprises a compound having the following formula:
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wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl), a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from 0.6-18 µg/kg (e.g. starting dose, titrated dose, and effective doses within 42 µg-1,260 µg (e.g., dose for 70 kg person; .6 µg x 70= 42 µg and 18 µg x 70 = 1,260 µg)); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain dry powder composition for inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; and 2) determine the lowest effective dose with reduced chance of adverse effects by titrating the dose of the active over hours to days to achieve an effective dose with reduced chance of adverse effects, as taught by Therapeutics. The person of ordinary skill in the art would have reasonably expected success because Malinin discloses a method for treating pulmonary hypertension (PH) (column 7, lines 10-11) that includes pulmonary administration of a composition comprising the prostacyclin compound that is administered once daily to the patient via including a dry powder inhaler (column 7, lines 24-28). Malinin discloses treprostinil alkyl esters Formula (A):
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wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl) (column 51, lines 55-58; column 52, Formula (A); column 53, compound C16-TR). Malinin discloses inhaled C16-TR (e.g., R1 is hexadecyl) at a dose of 0.6-18 µg/kg (e.g. dose for 70 kg person is 42 µg-1,260 µg) was well tolerated with no evidence of body weight and organ weight change after dosing for 14 consecutive days (column 82, lines 49-51). Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Regarding claims 240-242, in light of the disclosure of Malinin and the teachings of Armer, it would have been prima facie obvious to treat pulmonary hypertension in a human by administering once daily a dose of a dry powder enclosed in a capsule that comprises a compound having the following formula:
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wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl), a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from 0.6-18 µg/kg (e.g. starting dose, titrated dose, and effective doses within 42 µg-1,260 µg (e.g., dose for 70 kg person; .6 µg x 70= 42 µg and 18 µg x 70 = 1,260 µg)); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Malinin discloses that the therapeutic response of the patient is including improved exercise capacity (e.g., as measured by the six-minute walk test) compared to pretreatment (column 42, lines 24-32). The method which is prima facie obvious in light of the disclosure of Malinin and the teachings of Pan and Therapeutics, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler). Therefore, the method which is prima facie obvious in light of the disclosure of Malinin and the teachings of Pan and Therapeutics necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance by at least including about 5 meters during the administration period, compared to the patient’s distance walked in the six-minute walk distance prior to the administration period (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Thus, the claimed invention as a whole is clearly prima facie obvious over the teachings of the prior art.
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.
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 9,469,600 (hereafter ‘600) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claimed subject matter in the instant application is fully disclosed in the referenced US patent and would be covered by any patent granted on that referenced US patent.
Regarding instant claims 226, 229-230, 232, 235-239, claim 1 of ‘600 recites a prostacyclin compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claim 4 recites that n is 1. Therefore, the instant claims and the reference claims are drawn to identical compound with the same formula. The instant claims are drawn to a method of treating pulmonary hypertension in a patient comprising administering via a dry powder inhaler to the patient an effective amount of the compound during an administration period, wherein during administration period an initial dose of 80-160 µg of the compound is administered once daily in a single dosing session, and the initial dose is titrated to the patient’s highest tolerated dose. The referenced U.S. patent also disclosed (but did not claim) the compound as useful for treating pulmonary hypertension (PH), wherein WHO has classified PH into five groups (e.g., WHO Groups I-V (paragraph bridging columns 40 and 41)), and is administered via including a dry powder inhaler (column 1, lines 28-46; column 7, lines 27-46). The referenced U.S. patent also disclosed (but did not claim) that WHO Group III includes interstitial lung diseases and Group V includes sarcoidosis (paragraph bridging columns 40 and 41).
The referenced U.S. patent and the instant U.S. application are claiming a common subject matter, same compound of the same formula for use in treating pulmonary hypertension. For double patenting of previously disclosed, but newly claimed utility.
The referenced U.S. patent (‘600) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘600 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘600 recites a prostacyclin compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claim 4 recites that n is 1. ‘600 also disclosed (but did not claim) the compound as useful for treating pulmonary hypertension and is administered via including a dry powder inhaler (column 1, lines 28-46; column 7, lines 27-46). Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘600 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘600 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘600 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 9,255,064 (hereafter ‘064) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claimed subject matter in the instant application is fully disclosed in the referenced US patent and would be covered by any patent granted on that referenced US patent.
Regarding instant claims 226, 229-230, 232, 235-239, claim 1 of ‘064 recites a prostacyclin compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claim 4 recites that n is 1. Therefore, the instant claims and the reference claims are drawn to identical compound with the same formula. The instant claims are drawn to a method of treating pulmonary hypertension in a patient comprising administering via a dry powder inhaler to the patient an effective amount of the compound during an administration period, wherein during administration period an initial dose of 80-160 µg of the compound is administered once daily in a single dosing session, and the initial dose is titrated to the patient’s highest tolerated dose. The referenced U.S. patent also disclosed (but did not claim) the compound as useful for treating pulmonary hypertension (PH), wherein WHO has classified PH into five groups (e.g., WHO Groups I-V (paragraph bridging columns 39 and 40)), and is administered via including a dry powder inhaler (column 1, lines 29-48; column 7, lines 10-28). The referenced U.S. patent also disclosed (but did not claim) that WHO Group III includes interstitial lung diseases and Group V includes sarcoidosis (paragraph bridging columns 40 and 41).
The referenced U.S. patent and the instant U.S. application are claiming a common subject matter, same compound of the same formula for use in treating pulmonary hypertension. For double patenting of previously disclosed, but newly claimed utility.
The referenced U.S. patent (‘064) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘064 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘064 recites a prostacyclin compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claim 4 recites that n is 1. Therefore, the instant claims and the reference claims are drawn to identical compound with the same formula. The referenced U.S. patent also disclosed (but did not claim) the compound as useful for treating pulmonary hypertension (PH), wherein WHO has classified PH into five groups (e.g., WHO Groups I-V (paragraph bridging columns 39 and 40)), and is administered via including a dry powder inhaler (column 1, lines 29-48; column 7, lines 10-28). The referenced U.S. patent also disclosed (but did not claim) that WHO Group III includes interstitial lung diseases and Group V includes sarcoidosis (paragraph bridging columns 40 and 41). Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘064 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘064 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘064 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 17 of U.S. Patent No. 10,010,518 (hereafter ‘518) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Regarding instant claims 226, 229-230, 232, 235-236, claim 1 of ‘518 recites a method of treating pulmonary hypertension in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claims 2-6 of ‘518 recites the patient is a WHO Group I-V PH patient, respectively. Claim 7 of ‘518 recites administration via including a dry powder inhaler. Claim 8 of ‘518 recites that the PH is pulmonary arterial hypertension (PAH). Claim 17 of ‘518 recites administration once daily.
The referenced U.S. patent (‘518) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘518 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘518 recites a method of treating pulmonary hypertension in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claims 2-6 of ‘518 recites the patient is a WHO Group I-V PH patient, respectively. Claim 7 of ‘518 recites administration via including a dry powder inhaler. Claim 8 of ‘518 recites that the PH is pulmonary arterial hypertension (PAH). Claim 17 of ‘518 recites administration once daily. Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘518 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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647
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘518 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘518 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,526,274 (hereafter ‘274) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Regarding instant claims 226, 229-230, 232 and 237-238, claim 1 of ‘274 recites a method of treating pulmonary fibrosis (e.g., a species pulmonary hypertension) in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claims 2 and 10 of ‘274 recites administration via including a dry powder inhaler. Claim 3 of ‘274 recites administration once daily.
The referenced U.S. patent (‘274) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘274 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 230, 232 and 235-239, Roscigno teaches pulmonary hypertension is divided into five groups based on WHO criteria that is designated as WHO Groups 1 through 5 (paragraph [0005]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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386
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘274 recites a method of treating pulmonary fibrosis (e.g., a species pulmonary hypertension) in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5. Claims 2 and 10 of ‘274 recites administration via including a dry powder inhaler. Claim 3 of ‘274 recites administration once daily. Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘274 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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386
647
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘274 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘274 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23 and 25 of U.S. Patent No. 10,995,055 (hereafter ‘055) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Regarding instant claims 226, 229-230 and 235-236, claim 23 of ‘055 recites a method of treating pulmonary hypertension in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including linear hexadecyl; and n is an integer from 0 to 5, wherein the composition is in the form of a dry powder, wherein the administration is carried out via a dry powder inhaler. Claim 25 of ‘055 recites that the PH is pulmonary arterial hypertension (PAH).
The referenced U.S. patent (‘055) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘055 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 230, 232 and 235-239, Roscigno teaches pulmonary hypertension is divided into five groups based on WHO criteria that is designated as WHO Groups 1 through 5 (paragraph [0005]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
PNG
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386
647
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 23 of ‘055 recites a method of treating pulmonary hypertension in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including linear hexadecyl; and n is an integer from 0 to 5, wherein the composition is in the form of a dry powder, wherein the administration is carried out via a dry powder inhaler. Claim 25 of ‘055 recites that the PH is pulmonary arterial hypertension (PAH). Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘055 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
PNG
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386
647
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘055 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘055 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,795,135 (hereafter ‘135) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Regarding instant claims 226, 229, 232 and 237-238, claim 1 of ‘135 recites a method of treating pulmonary hypertension associated with interstitial lung disease in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5, wherein the composition is in the form of a dry powder, wherein the administration is carried out via a dry powder inhaler. Claim 2 recites that the patient is a WHO Group III PH patient.
The referenced U.S. patent (‘135) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘135 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 230, 232 and 235-239, Roscigno teaches pulmonary hypertension is divided into five groups based on WHO criteria that is designated as WHO Groups 1 through 5 (paragraph [0005]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
PNG
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386
647
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘135 recites a method of treating pulmonary hypertension associated with interstitial lung disease in a patient in need thereof comprising administering to the patient via pulmonary administration, a composition comprising effective amount of a compound of Formula (II):
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247
414
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wherein R1 is O; R2 is including hexadecyl; and n is an integer from 0 to 5, wherein the composition is in the form of a dry powder, wherein the administration is carried out via a dry powder inhaler. Claim 2 recites that the patient is a WHO Group III PH patient. Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘135 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
PNG
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386
647
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘135 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘135 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-8, 13-17 and 48 of U.S. Patent No. 11,458,098 (hereafter ‘098) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Regarding instant claims 226, 229-230, 232 and 235-239, claim 1 of ‘098 recites a dry powder composition that contains a compound of Formula (I):
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wherein R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl. Claim 7 of ‘098 recites a method for treating pulmonary hypertension in a patient in need thereof, comprising administering an effective amount of the dry powder composition of claim 1 to the lungs of the patient by inhalation via a dry powder inhaler. Claim 8 of ‘098 recites that the PH is pulmonary arterial hypertension. Claims 13-17 of ‘098 recites that the PH is characterized by WHO and includes groups 1-5 PH as characterized by WHO, respectively. Claim 48 of ‘098 recites that the pulmonary hypertension is associated with interstitial lung disease.
The referenced U.S. patent (‘098) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘098 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 230, 232 and 235-239, Roscigno teaches pulmonary hypertension is divided into five groups based on WHO criteria that is designated as WHO Groups 1 through 5 (paragraph [0005]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘098 recites a dry powder composition that contains a compound of Formula (I):
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wherein R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl. Claim 7 of ‘098 recites a method for treating pulmonary hypertension in a patient in need thereof, comprising administering an effective amount of the dry powder composition of claim 1 to the lungs of the patient by inhalation via a dry powder inhaler. Claim 8 of ‘098 recites that the PH is pulmonary arterial hypertension. Claims 13-17 of ‘098 recites that the PH is characterized by WHO and includes groups 1-5 PH as characterized by WHO, respectively. Claim 48 of ‘098 recites that the pulmonary hypertension is associated with interstitial lung disease. Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘098 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘098 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘098 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 29-31 of U.S. Patent No. 11,759,425 (hereafter ‘425) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Regarding instant claims 226-230, 232 and 235-239, claim 1 of ‘425 recites a method for treating pulmonary hypertension in a patient in need thereof, comprising administering an effective amount of a dry powder composition to the lungs of the patient by inhalation via a dry powder inhaler, wherein the dry powder composition contains a compound of Formula (I):
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wherein R1 is linear hexadecyl. Claim 29 recites that the PH is pulmonary arterial hypertension. Claim 30 recites that the PH is idiopathic pulmonary arterial hypertension. Claim 31 recites that the PH is associated with interstitial lung disease.
The referenced U.S. patent (‘425) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘425 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 230, 232 and 235-239, Roscigno teaches pulmonary hypertension is divided into five groups based on WHO criteria that is designated as WHO Groups 1 through 5 (paragraph [0005]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 1 of ‘425 recites a method for treating pulmonary hypertension in a patient in need thereof, comprising administering an effective amount of a dry powder composition to the lungs of the patient by inhalation via a dry powder inhaler, wherein the dry powder composition contains a compound of Formula (I):
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wherein R1 is linear hexadecyl. Claim 29 recites that the PH is pulmonary arterial hypertension. Claim 30 recites that the PH is idiopathic pulmonary arterial hypertension. Claim 31 recites that the PH is associated with interstitial lung disease. Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘425 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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,
wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘425 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘425 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51 and 63 of copending Application No. 18/360,514 (hereafter ‘514) in view of PAN (CN 1593414 A, date published: 16 March 2005), THERAPEUTICS INITIATIVE (“Dose Titration: Minimize to Maximize”, October 1995; cited in PTO-892 mailed 03/01/2024; hereafter Therapeutics) and ROSCIGNO (US 2019/0151332 A1, effectively filing date of 05 November 2018).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claimed subject matter in the instant application is fully disclosed in the referenced US application and would be covered by any patent granted on that referenced US application.
Regarding instant claims 226, 229, claim 51 of ‘514 recites a dry powder composition that contains a compound of Formula (I):
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wherein R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl. Claim 63 recites that R1 is linear hexadecyl. Therefore, the instant claims and the reference claims are drawn to identical compound with the same formula. The instant claims are drawn to a method of treating pulmonary hypertension in a patient comprising administering via a dry powder inhaler to the patient an effective amount of the compound during an administration period, wherein during administration period an initial dose of 80-160 µg of the compound is administered once daily in a single dosing session, and the initial dose is titrated to the patient’s highest tolerated dose. The referenced U.S. patent also disclosed (but did not claim) the compound as useful for treating pulmonary hypertension and is administered via including a dry powder inhaler (paragraphs [0030-0038]).
The referenced U.S. application and the instant U.S. application are claiming a common subject matter, same compound of the same formula for use in treating pulmonary hypertension. For double patenting of previously disclosed, but newly claimed utility.
The referenced U.S. patent (‘514) does not specifically claim or disclose dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. ‘514 does not specifically claim or disclose an initial dose of 80-160 µg of the compound and that the initial dose is titrated to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan, Therapeutics and Roscigno.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 260 and 262, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 4 wt%”, “from about 29 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 35 to about 70.5 wt%), respectively. Thus, the ranges in claim 226 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. The amount of 10%-70% hydrophobic amino acid including leucine to amount of 25%-89.9% of soluble carrier including mannitol (e.g., includes 10% to 25% which is 0.40 and ratios above and below 0.40) overlaps the leucine-to-mannitol weight ratio of about 0.40-to-1 recited in claim 262. Thus, the range in claim 262 is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively).
Therapeutics is primarily directed towards dose titration (see entire literature).
Regarding claims 226 and 245-247, Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page).
Roscigno is primarily directed towards a dry powder inhalation treatment for pulmonary arterial hypertension including a dose of dry particles comprising greater than 25 micrograms of Treprostinil in a capsule (abstract).
Regarding claims 226, 245, 249-250 and 256, Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]). Roscigno teaches that the patient is dosed including one time per day (e.g., a single dosing session once a day) (paragraph [0029]). Roscigno teaches that a dose of dry particles includes from about 75 micrograms to about 300 micrograms of treprostinil (paragraph [0028]).
Regarding claims 230, 232 and 235-239, Roscigno teaches pulmonary hypertension is divided into five groups based on WHO criteria that is designated as WHO Groups 1 through 5 (paragraph [0005]).
Regarding claims 240-242, Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]).
Regarding claim 254, Roscigno teaches providing the patient at least one capsule for use in the dry powder inhaler (paragraph [0029]).
Regarding claim 255, Roscigno teaches that the patient is dosed including one time per day and including greater than or equal to 200 micrograms of Treprostinil to a patient per breath (e.g. one inhalation for one session per day) (paragraph [0029]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a dry powder composition for administration by inhalation that has good fluidity and low hygroscopicity of the powder, which leads to excellent storage stability, by formulating the dry powder composition in the form of a dry powder composition produced by spray drying that is taught by Pan that includes the active in an amount of 0.1-5 wt%, a hydrophobic amino acid including leucine in an amount of 10-70 wt%, and a soluble carrier including mannitol in an amount of 25-89.9 wt%; 2) determine an effective dose for the subject and with minimum systemic exposure by titrating the dose as taught by Therapeutics; and used amounts of including greater than 25 micrograms as taught by Roscigno. The person of ordinary skill in the art would have reasonably expected success because claim 51 of ‘514 recites a dry powder composition that contains a compound of Formula (I):
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wherein R1 is tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl. Claim 63 recites that R1 is linear hexadecyl. Therefore, the instant claims and the reference claims are drawn to identical compound with the same formula. The instant claims are drawn to a method of treating pulmonary hypertension in a patient comprising administering via a dry powder inhaler to the patient an effective amount of the compound during an administration period, wherein during administration period an initial dose of 80-160 µg of the compound is administered once daily in a single dosing session, and the initial dose is titrated to the patient’s highest tolerated dose. The referenced U.S. patent also disclosed (but did not claim) the compound as useful for treating pulmonary hypertension and is administered via including a dry powder inhaler (paragraphs [0030-0038]). Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Therapeutics teaches starting with the lowest available dose and titration should occur over hours to days to achieve an effective dose with reduced chance of adverse effects (paragraph bridging the first and second page). Roscigno teaches an inhalation dry powder formulation of treprostinil. Roscigno teaches that the dry powder comprises including greater than 25 micrograms of treprostinil (paragraph [0028]).
Regarding claims 240-242, in light of the disclosure of claims and disclosure of ‘514 and the teachings of Pan, Therapeutics and Roscigno, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having structure II:
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wherein R1 is O; R2 is including hexadecyl; and n is an integer including 1, a hydrophobic amino acid including leucine, and a soluble carrier including mannitol; titrating the dose of the compound to higher doses over hours to days to determine an effective dose of the compound with reduced chance of adverse effects; wherein the dose of the compound includes from about 75 micrograms to about 300 micrograms (e.g., starting dose, titrated dose, and effective doses); wherein the amount of the compound is 0.1-5 wt%, the amount of the hydrophobic amino acid including leucine is 10-70 wt% and the amount of the soluble carrier including mannitol is 25-89.9 wt%. Roscigno teaches that treatment pulmonary arterial hypertension include improvement in the 6 minute walk distance (paragraph [0011]). The method which is prima facie obvious in light of the claims and disclosure of ‘514 and the teachings of Pan, Therapeutics and Roscigno, is substantially the same as the instantly claimed method (e.g., same patient population of subjects with pulmonary hypertension that is administered the same drug in an effective amount that is in a dry powder and delivered by a dry powder inhaler), therefore, the method which is prima facie obvious in light of the claims and disclosure of ‘514 and the teachings of Pan, Therapeutics and Roscigno necessarily has the same characteristics, e.g., improve exercise capacity of the subject during the administration period as measured by the six-minute walk distance (e.g., claims 240-242), absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
This is a provisional nonstatutory double patenting rejection.
Claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 226-227, 229, 243-251, 253, 255-256 and 258-259 of copending Application No. 18/034,619 (hereafter ‘619).
Regarding instant claims 226, 229, 245, 249-250, 255-256, 260 and 262, claim 226 of ‘619 recites a dry powder composition comprising the same compound as the compound of instant claim 226 in an amount of from about 0.5 wt% to about 5 wt% including a stereoisomer or a pharmaceutically acceptable salt thereof, wherein the R1 is hexadecyl, from about 25 wt% to about 61 wt% of leucine, and the balance being a sugar including mannitol, wherein the entirety of the compound, leucine and mannitol is 100 wt% and the dry powder composition is a spray dried dry powder composition. Claim 243 of ‘619 recites a method for treating pulmonary hypertension in a patient in need thereof, comprising administering via a dry powder inhaler to the patient once daily, and titrated from an initial dose to the patient’s highest tolerable dose. Claim 259 of ‘619 recites that a dose of the compound of Formula (I) is including 80 µg, 160 µg, 240 µg, 320 µg, or 640 µg.
Regarding instant claims 230, 232 and 235-239, claim 245 of ‘619 recites that the PH is group 1 PH as classified by WHO. Claim 246 of ‘619 recites that the PH is group 3 PH. Claim 249 of ‘619 recites that the PH is pulmonary arterial hypertension (PAH). Claim 250 of ‘619 recites that the PH is PH associated with interstitial lung disease (ILD). Claim 251 of ‘619 the same one or more lung conditions as the one or more lung conditions recited in instant claim 239.
Regarding instant claim 240, claim 252 of ‘619 recites that treating comprises improving exercise capacity of the patient during the administration period, compared to the exercise capacity of the patient prior to the administration period.
Regarding instant claims 241-242, claim 253 of ‘619 recites that improving exercise capacity comprises increasing the patient’s distance walked in the 6MWT by including at least about 5 meters or at least about 50 meters during the administration period, compared to the exercise capacity of the patient prior to the administration period.
Regarding instant claim 246-247, claim 255 of ‘619 recites that a dose is titrated to a higher dose after the patient has shown to tolerate for two or more days and claim 256 recites that two or more days includes two days, three days, four days, five days, six days or seven days.
Claim 254 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 226-227, 229, 243-251, 253, 255-256 and 258-259 of copending Application No. ‘619 as applied to claims 226, 229-230, 232, 235-242, 245-247, 249-250, 255-256, 260 and 262 above, and further in view of in view of PAN (CN 1593414 A, date published: 16 March 2005).
Regarding claim 254, the method of claim 226 is described above in section 22.
The claims of ‘619 do not specifically recite that the dose is present in one or more dry powder capsules. The deficiency is made up for by the teachings of Pan.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claim 254, Pan teaches capsule type inhalation powder that is suitable for inhalation (first and second paragraph on page 3 of the English translation).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat pulmonary hypertension in a human by administering a dry powder enclosed in a capsule once daily that comprises a compound having the following formula:
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wherein R1 is hexadecyl, from about 25 wt% to about 61 wt% of leucine, and the balance being a sugar including mannitol, wherein the entirety of the compound, leucine and mannitol is 100 wt% and the dry powder composition is a spray dried dry powder composition; titrating the initial dose to the patient’s highest tolerable dose; wherein the initial dose of the compound includes 80 µg. The person of ordinary skill in the art would have been motivated to make those modifications to obtain a dosage for administration by inhalation by putting the dry powder in a capsule for administration by inhalation, as taught by Pan. The person of ordinary skill in the art would have reasonably expected success because Pan teaches capsule type inhalation powder, wherein a dry powder is in a capsule, that is suitable for inhalation (first and second paragraph on page 3 of the English translation).
Response to Arguments and Declaration
Applicant’s arguments and the declaration will be addressed as they pertain to the new grounds of rejection above.
Applicant’s arguments and the declaration with respect to claim(s) 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 have been considered but are moot because the new ground of rejection relies on a different combination of references (e.g., Malinin in view of Pan and Therapeutics), which was necessitated by the claim amendments filed on 10 December 2025, and does not rely on the combination of references applied in the prior rejection of record for the matter specifically challenged in the argument and declaration.
Thus, for the reasons presented above claims 226, 229-230, 232, 235-242, 245-247, 249-250, 254-256, 260 and 262 are rejected under 35 U.S.C. 103(a) and on the ground of nonstatutory double patenting.
Conclusion and Correspondence
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600