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 .
Claims 23-48 have been presented for examination on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 23-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 23-48 are drawn to a composition or a method for treating … in a subject, wherein the composition comprises an inhibitor of deiodinase (D3). However, the Specification does not provide sufficient disclosure to support any and all inhibitors of deiodinase (D3), as encompassed by the claims. The Specification states:
“One exemplary second drug is an inhibitor of D3, such as, for example, iopanoic acid.” (See published Spec at [0073]).
This recitation is not adequate support for all inhibitors of D3.
This is a new matter rejection.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claims 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Mousa et al (US 20140199376) in view of St. Germain et al (US 20110159010).
Mousa et al teach compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs (See abstract). Thyroid hormones include L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) (See [0003] and [0014]).
Regarding claim 23, Mousa et al disclosure compositions (i.e., angiogenic agents) that include thyroid hormone, and analogs conjugated to a polymer. Examples of the thyroid hormone analogs include levothyroxine (T4), triiodothyronine (T3), etc, (See [0023]) and wherein the said pharmaceutical formulations include the angiogenic agents in a pharmaceutically acceptable carrier, and suitable excipients (See [0024]). "Pharmaceutically acceptable carrier" includes buffered normal saline (See [0147]). "Additional ingredients" include excipients; aqueous vehicles and solvents; buffers; etc; (See [0148]).
Regarding claims 24-25, Mousa et al disclosure the said therapeutic agents (i.e., polymeric thyroid hormone analogs) may be provided to an individual by any suitable means, directly or systemically. The agent may be provided parenterally, intranasally or by aerosol administration. The agent preferably comprises part of an aqueous or physiologically compatible fluid suspension or solution. Wherein the polymeric thyroid hormone analogs and a carrier or vehicle which can comprise normal physiologic saline (e.g., 9.85% aqueous NaCl, 0.15M, pH 7-7.4) (See [0328]).
Mousa et al also teach that the formulations were adjusted to a pH of 7 or 6.8 or 7.4 by NaCl or a buffer (See [0375], [0385] and [0550]).
It is also disclosed that formulations for inhalation administration contain as excipients, for example, lactose, or may be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or oily solutions for administration in the form of nasal drops, or as a gel to be applied intranasally (See [0330] and [0333]).
"Effective amount" includes from about 0.01 mg/kg/day to about 500 mg/kg/day, advantageously from about 0.1 mg/kg/day to about 100 mg/kg/day. Of the active substance. Further, the dosages of the active substance can be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation (See [0146]).
Mousa et al do not disclose the compositions comprising an inhibitor of deiodinase (D3). This is known in the art as shown by St. Germain et al.
St. Germain et al teach methods for treating obesity or lowering blood glucose levels in a subject with an agent that inhibits the expression or activity of type III deiodinase (See abstract).
Regarding claim 23, St. Germain et al teach that D3 levels are decreased or reduced using an agent which inhibits the expression or activity of D3, which can be proteins, antibodies, antibody fragments, aptamers, peptides, nucleic acids, oligonucleotides, siRNA, ribozymes, etc (See [0013]). Agents including iopanoic acid and iodoacetate exhibits D3 inhibitory activity (See [0019]).
St Germain et al teach that D3 functions exclusively as a 5-deiodindinase and catalyzes the conversion of T4 and T3 to inactive metabolites (rT3 and T2) (See [0003]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of St. Germain et al with that of Mousa et al to arrive at the instant invention.
One of ordinary skill in the art would have been motivated to do so because Mousa et al teach a method of making a pharmaceutical composition comprising triiodothyronine, carriers and a buffer with a pH of from 5.5-8.5. St. Germain et al also teach compositions comprising an agent that decreases the expression or activity of type III deiodinase (D3) and disclose the relationship between T3 and/or T4 and D3. That is St. Germain et al teach that D3 can catalyze the conversion of T3 or T4 to their inactive metabolites and that and inhibitor of D3 would be effective in preventing this conversion.
Thus, one of ordinary skill in the art would have had a reasonable expectation of success from incorporating St. Germain et al’s D3 inhibitors into Mousa et al’s formulations to provide an effective composition and improve the treatment.
Claims 23-26 and 28-43 are rejected under 35 U.S.C. 103 as being unpatentable over Mousa et al (US 20140199376) in view of St. Germain et al (US 20110159010) and Kaminski et al (US 20170105956).
Mousa et al and St. Germain et al’s teachings are delineated above and incorporated herein.
The combined references do not disclose the compositions for administration via a nebulizer or the treatments being inflammation of the lung tissue or lung injury. These are known in the art as shown by Kaminski et al.
Kaminiski et al teach a method of preventing or treating a fibrotic lung disease in a subject, comprising administering to the subject a thyroid hormone by inhalation and/or aerosolization, and compositions (See abstract and [0006]).
Studies in murine models have shown that exogenous administration of thyroid hormones (T4-thyroxine and its potent derivative-triiodothyronine-T3) accelerate surfactant production, alveolar formation and fetal lung maturation (See [0004]).
Regarding claims 24-26, 29-31, 37-39 (and 45-46), Kaminiski et al disclose that the said method comprises administering to the subject a therapeutically effective amount of at least one thyroid derivative using an administration route selected from the group consisting of nasal, inhalational, intratracheal, intrapulmonary, intrabronchial, and inhalation and wherein the inhalation is by aerosolization, nebulization or atomization (See [0007], [0084]-[0085] and [0089]).
The said method comprises assaying lung tissue of the subject for DIO2 levels, wherein, if DIO2 levels in the lung tissue of the subject are upregulated with respect to a subject not afflicted with the disease, the subject is administered a therapeutically effective amount of T4 hormone using an administration route selected from the group consisting of nasal, inhalational, intratracheal, intrapulmonary, intrabronchial, and inhalation (See [0008]).
The said thyroid derivative comprises a thyroid hormone comprising T3 hormone or T4 hormone (See [0009]).
Regarding claims 28, 34-36, and 43, Kaminski et al disclose a method for preventing or treating a fibrotic lung disease in a subject using an administration route selected from the group consisting of nasal, inhalational, intratracheal, intrapulmonary, intrabronchial, and inhalation, wherein the thyroid hormone comprises T3 hormone or T4 hormone (See [0013]) and that wherein the thyroid hormone T3 is directly delivered into the lung using an inhaler. This allows for effective delivery of an optimal drug dose within areas of injured lung, maximizing its therapeutic effects and minimizing potential side effects arising from systemic administration (See [0022]).
Regarding claims 28, 34-36, and 43, Kaminski et al discloses that the said diseases and conditions that may cause pulmonary fibrosis as a secondary effect include: inhalation of environmental and occupational pollutants (asbestosis, silicosis and gas exposure); hypersensitivity pneumonitis, most often resulting from inhaling dust contaminated with bacterial, fungal, or animal products; cigarette smoking; connective tissue diseases such as rheumatoid arthritis, SLE; scleroderma, sarcoidosis and Wegener's granulomatosis; infections; medications such as amiodarone, bleomycin, etc; and radiation therapy to the chest (See [0036]-[0037]).
Regarding claims 28 and 36, Kaminski et al also disclose that “as reported herein, animal studies include the delivery of T4 to mouse injured lung following bleomycin exposure via repeated inhalations during various time points of the disease course. In the preventive approach; T4 is inhaled at day 0 following bleomycin exposure. In the therapeutic approach, T4 is repeatedly inhaled (every day) at days 7-14 (inflammatory stage) and at days 14-21 (fibrotic stage) following bleomycin exposure” (See [0023]).
The said "pharmaceutically acceptable carrier" encompasses a carrier material or composition such as a liquid or solid filler, diluent, excipient, buffering agents, such as magnesium hydroxide and aluminum hydroxide; phosphate buffer solutions; etc (See [0041]).
It is further stated that the said pharmaceutical compositions formulated for pulmonary delivery may also provide the active ingredient in the form of droplets of a solution or suspension and may conveniently be administered using any nebulization or atomization device. Such formulations may further comprise one or more additional ingredients including, a buffering agent, a surface active agent, etc. The droplets provided by this route of administration in certain embodiments have an average diameter in the range from about 0.1 to about 200 nanometers (See [0089]).
An effective amount of the therapeutic compound necessary to achieve a therapeutic effect may vary according to factors such as the state of the disease or disorder in the patient; the age, sex, and weight of the patient; and the ability of the therapeutic compound to treat a disease or disorder. A non-limiting example of an effective dose range for the said therapeutic compound is from about 1 and 5,000 mg/kg of body weight/per day. A suitable dose of the compound may be in the range of from about 0.01 mg to about 5,000 mg per day (See [0067]-[0071]).
Regarding claims 32-34 and 40-42, Kaminski et al teach that the dosages of the therapeutic formulations may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation (See [0066}, and that a tested group of infants receiving thyroid replacement therapy had respiratory distress syndrome (RDS) (See [0004]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Kaminski et al with that of Mousa et al and St. Germain et al to arrive at the instant invention.
One of ordinary skill in the art would have been motivated to do so because Mousa et al teach a method of making a pharmaceutical composition comprising triiodothyronine, carriers and a buffer with a pH of from 5.5-8.5. St. Germain et al also teach compositions comprising an agent that decreases the expression or activity of type III deiodinase (D3) and disclose the relationship between T3 and/or T4 and D3. That is St. Germain et al teach that D3 can catalyze the conversion of T3 or T4 to their inactive metabolites and that and inhibitor of D3 would be effective in preventing this conversion.
Thus, one of ordinary skill in the art would have had a reasonable expectation of success from incorporating St. Germain et al’s D3 inhibitors into Mousa et al’s formulations to provide an effective composition and improve the treatment.
Kaminski et al teach a method of making a pharmaceutical composition comprising triiodothyronine which are said to be effective in treating lung diseases and conditions such as inflammation and fibrosis, and can be effectively and directly administered to the lungs.
Therefore, one of ordinary skill in the art would have had a reasonable expectation of success from combining Kaminski et al’s teaching on making a formulation that is both effective and safe to treat lung inflammation and injury with the teachings of Mousa et al and St. Germain et al to effectively treat subjects suffering from lung diseases and delivered to the lungs directly.
Claims 23 and 44-48 are rejected under 35 U.S.C. 103 as being unpatentable over Mousa et al (US 20140199376) in view of St. Germain et al (US 20110159010) and Morkin (6,716,877).
Mousa et al and St. Germain et al’s teachings are delineated above and incorporated herein.
The combined references do not disclose the compositions for the treatment of congestive heart failure. This is known in the art as shown by Morkin et al.
Morkin teaches a method for treating a patient having congestive heart failure by administering a therapeutically effective amount of 3',3,5-triiodothyropropionic acid (TRIPROP) or 3.5.3',5'- tetraiodothyropropionic acid (TETRAPROP) (See abstract).
Regarding claim 44 and 47-48, Morkin teaches the use of 3,5- diiodothyropropionic acid (DITPA), a thyroid hormone analog, for treating patients with congestive heart failure, which like thyroid hormone binds to nuclear T receptors. Other DITPA-like compounds having similar utility, such as 3',3,5- triiodothyropropionic acid (or “TRIPROP”) and the tetraiodo derivative, 3,5,3',5'-tetraiodothyropropionic acid (or “TETRAPROP”) (See Col. 2, lines 40-45 and Col. 3, lines 8-19).
Regarding claims 45-46, Morkin teaches that TRIPROP or TETRAPROP may be administered in the form of inhalation or insufflation. For administration by inhalation or insufflation a solution of TRIPROP or TET RAPROP is conveniently delivered in the form of an aerosol Spray presentation from pressurized packs or nebulizer (See Col. 4, lines 19-25).
For treating congestive heart failure, the TRIPROP can be administered at doses between 0.014 and 0.056 mg/kg, or 1 to 4 mg per day for a 70 kg person. (See Col. 4, lines 41-44).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Morkin with that of Mousa et al and St. Germain et al to arrive at the instant invention.
The reasons for combining St. Germain et al with Musa et al is stated above and incorporated herein. Furthermore, one of ordinary skill in the art would have been motivated to combine the teachings of Morkin because Morkin teaches a method of treating congestive heart failure in a subject by administration to the subject an effective amount of a thyroid derivative including 3',3,5- triiodothyropropionic acid by inhalation. Thus, one of ordinary skill in the art is more than motivated to incorporate Morkin’s teachings into that of the combined references and determine that the same formulations are also effective in treating congestive heart failure.
Thus, one of ordinary skill in the art would have had a reasonable expectation of success from combining Morkin, St. Germain et al and Mousa et al’s teaching on making a formulation that is both effective and safe in treating congestive heart failure.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 23-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,458,094 in view of St. Germain et al (US 20110159010).
The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims. The examined claims would have been obvious over the reference claims in view of St. Germain et al.
Specifically, the examined claims are drawn to a composition comprising a salt of triiodothyronine in an amount of from 100 ng to 2 mg, an inhibitor of deiodinase-3 (D3) and a buffer (claim 23); a method of treating inflammation of the lung tissue (claim 28), a method of treating lung injury (claim 36) and a method of treating congestive heart failure (claim 44) in a subject by administering to the pulmonary tract of the subject the composition of claim 23.
Reference claims are drawn to a composition for administering directly to the lung of a subject, the composition comprising: a salt of triiodothyronine in an amount effective to provide a lung-delivered dose of from 100 ng to 2 mg; and a pharmaceutically acceptable buffer; a method of treating a subject having, or at risk of having inflammation of lung tissues, and a method of treating a subject having, or at risk of having lung injury. It is noted that said lung inflammation may be a symptom of congestive heart failure or structural lung disease (See claims 11 or 19).
The difference between the reference claims and instant claims is that the reference claims do not recite the presence of an inhibitor of deiodinase-3 (D3). However, the difference is an obvious modification to the reference claims especially in view of the teachings of St. Germain et al, as it is disclosed and suggests adding a D3 inhibitor to improve the treatment with a thyroid treatment method.
Claims 44-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,883,528 in view of St. Germain et al (US 20110159010).
The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims. The examined claims would have been obvious over the reference claims in view of St. Germain et al.
Specifically, the examined claims are drawn to a composition comprising a salt of triiodothyronine in an amount of from 100 ng to 2 mg, an inhibitor of deiodinase-3 (D3) and a buffer (claim 23); and a method of treating congestive heart failure (claim 44) in a subject by administering to the pulmonary tract of the subject the composition of claim 23.
Reference claims are drawn to a method of treating congestive heart failure comprising administering to the pulmonary tract of the subject a composition comprising an amount of triiodothyronine (T3) effective to ameliorate lung inflammation or pulmonary edema, wherein the composition comprises a salt of triiodothyronine in an amount effective to provide a lung-delivered dose of from 100 ng to 2 mg; and a pharmaceutically acceptable buffer wherein the composition delivered to the lung has a pH from 5.5 to 8.5 and a maximum volume of no more than 0.30 ml per 1.67 g wet lung weight per dose.
The difference between the reference claims and instant claims is that the reference claims do not recite the presence of an inhibitor of deiodinase-3 (D3). However, the difference is an obvious modification to the reference claims especially in view of the teachings of St. Germain et al, as it is disclosed and suggests adding a D3 inhibitor to improve the treatment with a thyroid treatment method. The Ph and dosage volume of the reference clams is encompassed by the examined claims.
Claims 23-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 7-11, 21-23 of copending Application No. 17/914,942 (US 20230147865) in view of St. Germain et al (US 20110159010) and Kaminski et al (US 20170105956).
The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims. The examined claims would have been obvious over the reference claims in view of St. Germain et al and Kaminski et al.
Specifically, the examined claims are drawn to a composition comprising a salt of triiodothyronine in an amount of from 100 ng to 2 mg, an inhibitor of deiodinase-3 (D3) and a buffer (claim 23); a method of treating inflammation of the lung tissue (claim 28), a method of treating lung injury (claim 36) and a method of treating congestive heart failure (claim 44) in a subject by administering to the pulmonary tract of the subject the composition of claim 23.
Reference claims are drawn to a method of treating acute respiratory distress syndrome (ARDS) in a subject comprising administering an initial dose of T3 directly to the sinopulmonary tract of the subject measuring the serum levels and providing a second dose of T3.
The difference between the reference claims and instant claims is that the reference claims 1- do not recite the presence of an inhibitor of deiodinase-3 (D3) and recite a method of treating ARDS in two steps. Regarding 1, the difference is an obvious modification to the reference claims especially in view of the teachings of St. Germain et al, as it is disclosed and suggests adding a D3 inhibitor to improve the treatment with a thyroid treatment method. Regarding 2, it is an obvious modification of the instant claims because it is routine to measure the serum levels of a hormone therapy to determine if further doses are required. It is also noted that a lung inflammation is clinical sign of ARDS. Accordingly, the same method steps would have treated all recited conditions.
This is a provisional nonstatutory double patenting rejection.
Claims 23-48 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached on M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616