Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Claims 1-22 are currently pending.
Specification
The disclosure is objected to because there are no matching descriptions for Figures 3F and 3G of applicant’s drawings filed 5/30/2024.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Interpretation
For the purposes of examination, demyelination and “dysmyelination” as claimed are considered distinct processes, wherein the former refers to the undoing or destruction of functional myelin sheaths (multiple sclerosis, etc.) whereas the latter refers to the incomplete formation or malformation of the myelin sheaths (X-linked adrenoleukodystrophy, adult Refsum disease, etc.).
Claim Objections
Claims 4 and 6-18 are objected to because “The method of anyone of claim 1” should instead read “ The method of claim 1”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 1-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for alleviating “a disease, disorder, or condition associated with or suspected of being associated with dysmyelination”, does not reasonably provide enablement for the treatment, which includes the prevention and inhibition, of any of such diseases including Pitt-Hopkins Syndrome (PTHS). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention (1) and breadth of the claims (6)
The nature of the invention and breadth of Claims 1-22 is the treatment, including prevention and inhibition, of a disease, disorder, or condition associated with or suspected of being associated with dysmyelination including PTHS. Page 10 of the specification provides that the term the term "treating" can include reversing, alleviating, inhibiting the progression of, preventing or reducing the likelihood of the disease, disorder, or condition to which such term applies, or one or more symptoms or manifestations of such disease, disorder or condition.”
The state of the prior art (2) and the predictability or lack thereof in the art (3)
Sweatt (Experimental & Molecular Medicine (2013) 45, e21, 1-15) teaches “Pitt–Hopkins Syndrome (PTHS) is a rare disorder characterized by intellectual disability (ID), ‘atypical’ autistic characteristics, and hyperventilation. PTHS is caused by heterozygous hypomorphic or null mutation or deletion of the transcription factor 4 (TCF4) gene on human chromosome 18” (Page 1). Applicant describes the same on Page 1 of the specification. Sobetirome is a thyromimetic drug that binds TRbeta1 and is not implicated in chromosomal or SNP mutations which cause the disease. Therefore, Sweatt’s description of the etiology of PTHS precludes sobetirome from “preventing” the genus of diseases as claimed because its onset is caused by genetic factors rather than caused directly by TRbeta1 activity.
It is unclear how such diseases broadly related to dysmyelination, which are often caused by genetic factors, can be prevented by therapeutics which address symptoms following the initiation of the disease.
The amount of direction or guidance present (4) and the presence or absence of working examples (5)
Example 1, Page 22+, details the treatment of mice in a PTHS model. However, the model describes “restoring” myelination defects, not preventing such defects. Further, no explication of how sobetirome would remedy the gene deletion or mutation causing downregulation of TCF4 is provided.
The quantity of experimentation needed (7)
The quantity of experimentation needed is extremely difficult, novel, and undue experimentation; the ability of the method to prevent or inhibit PTHS or diseases related to dysmyelination is nearly impossible to determine and not at all enabled by the experiments disclosed in the specifications of the application.
The level of the skill in the art (8)
The level of skill in the art is high; however, even to a person of high skill in the pharmaceutical arts, sobetirome would not be expected to prevent diseases caused by genetic factors.
Thus, the specification fails to provide sufficient support of the broad use of the method of the instant claims for “treating” the claimed diseases.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and 22 recite “sobetirome…or derivative thereof”. The term “derivative” is undefined in applicant’s specification. “Derivative” is unclear and fails to establish the metes and bounds of the claim because there is no clear limitation defining what is and is not considered a derivative. How much structural modification is acceptable before a compound is no longer considered a “derivative” of sobetirome? Claims 2-21 are rejected by virtue of dependency.
Claim 5 recites the limitation “the one or more conditions associated with Pitt-Hopkins Syndrome”. There is insufficient antecedent basis for this limitation in the claim because the claims upon which Claim 5 depends do not describe “one or more conditions”. Therefore it is unclear what “the” refers to in the rejected claim.
Claim 5 recites “seizures (epilepsy)”. It is unclear whether the parenthetical is further limiting the preceding term “seizures” or is merely exemplary of a type of seizures. Applicant must delete the parenthetical or clearly incorporate it as a limitation of the claim.
Claims 19 and 21 recite “unknown pro-myelinating compound” and “unknown muscarinic receptor antagonist”. The word unknown makes the metes and bounds of the secondary therapeutic explicitly unclear because one of ordinary skill in the art cannot know whether such a therapeutic is known to function as claimed if it is by definition “unknown.”
Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention. “The use of sobetirome” is ambiguous, describing a compound or possibly a method of use. Use is not a category of invention. Applicant is requested to clearly distinguish a category of invention under 35 USC 101 for each claim.
Claim Rejections - 35 USC § 112(d)
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.
Claim 21 is 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 21 describes “any known…muscarinic receptor antagonist” which is the same scope as Claim 20, upon which 21 depends. Therefore, Claim 21 does not further limit the scope of the genus of therapeutic agent which is described in Claim 20.
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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 22 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall clearly into at least one of the four categories of patent eligible subject matter because a use claim is not considered a method for lack of distinct steps. Rather, the claims as presented can be drawn to two distinct categories of invention: composition of matter and method. Further, "use" claims that do not clearly purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961) ("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101"). See MPEP 2173.05(q).
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 11-17, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hartley (WO2014178931).
Hartley teaches a method of treating X-linked adrenoleukodystrophy, adult Refsum disease or Krabbe disease, neurodevelopmental disorders, comprising administering sobetirome (Claims 1-7). Adult Refsum disease, for example, commonly occurs in childhood/adolescence and progresses into adulthood (Page 4). Sobetirome is administered via the claimed routes once or multiple times daily (Page 16). Regarding Claim 17, the limitation “wherein the prodrug of sobetirome comprises Sob-AM2” merely limits the prodrug form but does not limit the agent of Claim 1 to a prodrug. Therefore, Claim 17 further limits Claim 1 in that the acceptable agent to be administered is “sobetirome or a prodrug, wherein the prodrug is Sob-AM2, or a derivative thereof”. Hartley teaches sobetirome and therefore reads on Claim 17.
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.
Claims 1-3, 11-19, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Hartley (WO2014178931).
Hartley teaches a method of treating X-linked adrenoleukodystrophy, adult Refsum disease or Krabbe disease, neurodevelopmental disorders, comprising administering sobetirome (Claims 1-7). Adult Refsum disease, for example, commonly occurs in childhood/adolescence and progresses into adulthood (Page 4). Sobetirome is administered via the claimed routes once or multiple times daily (Page 16). Regarding Claim 17, the limitation “wherein the prodrug of sobetirome comprises Sob-AM2” merely limits the prodrug form but does not limit the agent of Claim 1 to a prodrug. Therefore, Claim 17 further limits Claim 1 in that the acceptable agent to be administered is “sobetirome or a prodrug, wherein the prodrug is Sob-AM2, or a derivative thereof”. Hartley teaches sobetirome and therefore reads on Claim 17.
Regarding Claims 18-19, Hartley teaches remyelination comprises administering T3 (Page 1). Remyelination with sobetirome in diseases with insufficient myelination or underdeveloped myelin sheaths is contemplated too (Page 2, Lines 1-11). Therefore, one of skill in the art seeking to treat diseases associated with dysmyelination or insufficient myelination would administer T3 with sobetirome as suggested by Hartley and expect success in recovering myelin sheath function because both T3 and sobetirome are taught to be use for this purpose. Further, in a related disease, multiple sclerosis, both agents are administered to reverse demyelination and promote remyelination of healthy sheaths (Page 24).
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Hartley as applied to Claims 1-3, 11-19, and 22 in further view of Abiraman (The Journal of Neuroscience, February 25, 2015 • 35(8):3676–3688).
The teachings of Hartley are set forth above and incorporated by reference herein.
Hartley does not discuss the use of a muscarinic receptor antagonist.
Abiraman teaches “[u]sing solifenacin, an FDA-approved drug, we show that adjunct therapy increased the rate of myelination” and “[s]olifenacin promotes hOPC differentiation and myelination” (Pages 3676 and 3684).
In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” See MPEP 2144.06. The compounds of Hartley and Abiraman are all directed toward the healthy remyelination of insufficiently myelinated or dysmyelinated sheaths. Therefore, it is prima facie obvious to form a composition comprising the examined compound and solfenacin to promote healthy myelination in diseases described in Hartley associated with dysmyelination. One of skill in the art would expect success in treating the diseases with both agents because insufficient myelination is corrected by both sobetirome and solifenacin.
Claims 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hartley as applied to Claims 1-3, 11-19, and 22 in further view of Phan (Nature Neuroscience volume 23, pages375–385 (2020)).
The teachings of Hartley are set forth above and incorporated by reference herein.
Hartley does not teach the role of myelination in PTHS.
Phan teaches “reduced myelination in the PTHS mouse model was due directly to Tcf4 mutation” and “defects in myelination are a primary pathophysiology in PTHS” (Pages 383-384). Further, “Tcf4 mutation leads to deficits in myelination” (Page 376).
One of ordinary skill in the art seeking to treat PTHS and symptoms resulting therefrom as described in examined Claim 5, informed by Hartley teaching sobetirome promotes healthy myelination in diseases associated with de- or dysmyelination and Phan teaching PTHS’s primary pathophysiology is related to myelination defects, would seek to use sobetirome to correct the undermyelination experienced by those afflicted by PTHS. The same artisan would expect success in doing so because of the related pathologies of the specific diseases described in Hartley and Phan as well as sobetirome’s known therapeutic uses in promoting healthy myelination of axon sheaths before the effective filing date of the examined claims.
Regarding Claims 6-10, one of skill in the art would expect success in treating any one of the TCF4 mutant subpopulations because disruption of TCF4, whether through chromosomal deletion, SNP nonsense mutation, gene deletion, is expected to lead “to deficits in myelination” as taught above.
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.
NONPROVISIONAL:
1. Claims 1-16 and 18-22 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-8 of U.S. Patent No. 9701650 (hereinafter referred to as Scanlan) in view of Hartley (WO2014178931), Abiraman (TheJournalofNeuroscience, February 25, 2015 • 35(8):3676–3688), and Phan (Nature Neuroscience volume 23, pages375–385 (2020)).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a sobetirome and prodrugs thereof for the treatment of dysmyelinating diseases.
Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Scanlan teaches a sobetirome prodrug (Claim 1). The prodrug is used in treating X-linked ALD, a dysmyelinating disease (Col 2, Lines 64+). Another neurodegenerative disease to be treated is adult Refsum disease with onset in childhood or adolescence (Col 4, Lines 22-33). Routes of administration include oral, intravenous, and others (Col 10, Lines 38-51; Col 28). Administration may be hourly (multiple times per day) or daily (Col 28, Lines 17-30).
Scanlan fails to teach co-administration with pro-myelinating agents or muscarinic receptor antagonists, specific treatment of PTHS, and TCF4 mutation in PTHS.
Regarding Claims 18-19, Hartley teaches remyelination comprises administering T3 (Page 1). Remyelination with sobetirome in diseases with insufficient myelination or underdeveloped myelin sheaths is contemplated too (Page 2, Lines 1-11). Diseases include X-linked ALD, adult Refsum disease, and Krabbe disease (Claims 1-7). Therefore, one of skill in the art seeking to treat diseases associated with dysmyelination or insufficient myelination would administer T3 with sobetirome as suggested by Hartley and expect success in recovering myelin sheath function because both T3 and sobetirome are taught to be use for this purpose. Further, in a related disease, multiple sclerosis, both agents are administered to reverse demyelination and promote remyelination of healthy sheaths (Page 24).
Abiraman teaches “[u]sing solifenacin, an FDA-approved drug, we show that adjunct therapy increased the rate of myelination” and “[s]olifenacin promotes hOPC differentiation and myelination” (Pages 3676 and 3684).
In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” See MPEP 2144.06. The compounds of Scanlan, Hartley, and Abiraman are all directed toward the healthy remyelination of insufficiently myelinated or dysmyelinated sheaths. Therefore, it is prima facie obvious to form a composition comprising the examined compound, T3, and solfenacin to promote healthy myelination in diseases described in Scanlan and Hartley associated with dysmyelination. One of skill in the art would expect success in treating the diseases with both agents because insufficient myelination is corrected by sobetirome, T3, and solifenacin.
Phan teaches “reduced myelination in the PTHS mouse model was due directly to Tcf4 mutation” and “defects in myelination are a primary pathophysiology in PTHS” (Pages 383-384). Further, “Tcf4 mutation leads to deficits in myelination” (Page 376).
One of ordinary skill in the art seeking to treat PTHS and symptoms resulting therefrom as described in examined Claim 5, informed by Scanlan teaching sobetirome promotes healthy myelination in diseases associated with de- or dysmyelination and Phan teaching PTHS’s primary pathophysiology is related to myelination defects, would seek to use sobetirome to correct the dysmyelination experienced by those afflicted by PTHS. The same artisan would expect success in doing so because of the related pathologies of the specific diseases described in Scanlan, Hartley, and Phan as well as sobetirome’s known therapeutic uses in promoting healthy myelination of axon sheaths before the effective filing date of the examined claims.
Regarding Claims 6-10, one of skill in the art would expect success in treating any one of the TCF4 mutant subpopulations because disruption of TCF4, whether through chromosomal deletion, SNP nonsense mutation, gene deletion, is expected to lead to “to deficits in myelination” as taught above.
Since both claim sets teach administering sobetirome or prodrugs thereof for the treatment of diseases associated with dysmyelination, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Scanlan.
2. Claims 1-16 and 18-22 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-11 of U.S. Patent No. 10392356 (hereinafter referred to as Scanlan) in view of Hartley (WO2014178931), Abiraman (TheJournalofNeuroscience, February 25, 2015 • 35(8):3676–3688), and Phan (Nature Neuroscience volume 23, pages375–385 (2020)).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a sobetirome and prodrugs thereof for the treatment of dysmyelinating diseases.
Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Scanlan teaches a sobetirome prodrug (Claim 1). The prodrug is used in treating X-linked ALD, a dysmyelinating disease (Col 2, Lines 64+). Another neurodegenerative disease to be treated is adult Refsum disease with onset in childhood or adolescence (Col 4, Lines 22-33). Routes of administration include oral, intravenous, and others (Col 10, Lines 38-51; Col 29, Lines 13-33). Administration may be hourly (multiple times per day) or daily (Col 29, Lines 33-47).
Scanlan fails to teach co-administration with pro-myelinating agents or muscarinic receptor antagonists, specific treatment of PTHS, and TCF4 mutation in PTHS.
Regarding Claims 18-19, Hartley teaches remyelination comprises administering T3 (Page 1). Remyelination with sobetirome in diseases with insufficient myelination or underdeveloped myelin sheaths is contemplated too (Page 2, Lines 1-11). Diseases include X-linked ALD, adult Refsum disease, and Krabbe disease (Claims 1-7). Therefore, one of skill in the art seeking to treat diseases associated with dysmyelination or insufficient myelination would administer T3 with sobetirome as suggested by Hartley and expect success in recovering myelin sheath function because both T3 and sobetirome are taught to be use for this purpose. Further, in a related disease, multiple sclerosis, both agents are administered to reverse demyelination and promote remyelination of healthy sheaths (Page 24).
Abiraman teaches “[u]sing solifenacin, an FDA-approved drug, we show that adjunct therapy increased the rate of myelination” and “[s]olifenacin promotes hOPC differentiation and myelination” (Pages 3676 and 3684).
In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” See MPEP 2144.06. The compounds of Scanlan, Hartley, and Abiraman are all directed toward the healthy remyelination of insufficiently myelinated or dysmyelinated sheaths. Therefore, it is prima facie obvious to form a composition comprising the examined compound, T3, and solfenacin to promote healthy myelination in diseases described in Scanlan and Hartley associated with dysmyelination. One of skill in the art would expect success in treating the diseases with both agents because insufficient myelination is corrected by sobetirome, T3, and solifenacin.
Phan teaches “reduced myelination in the PTHS mouse model was due directly to Tcf4 mutation” and “defects in myelination are a primary pathophysiology in PTHS” (Pages 383-384). Further, “Tcf4 mutation leads to deficits in myelination” (Page 376).
One of ordinary skill in the art seeking to treat PTHS and symptoms resulting therefrom as described in examined Claim 5, informed by Scanlan teaching sobetirome promotes healthy myelination in diseases associated with de- or dysmyelination and Phan teaching PTHS’s primary pathophysiology is related to myelination defects, would seek to use sobetirome to correct the dysmyelination experienced by those afflicted by PTHS. The same artisan would expect success in doing so because of the related pathologies of the specific diseases described in Scanlan, Hartley, and Phan as well as sobetirome’s known therapeutic uses in promoting healthy myelination of axon sheaths before the effective filing date of the examined claims.
Regarding Claims 6-10, one of skill in the art would expect success in treating any one of the TCF4 mutant subpopulations because disruption of TCF4, whether through chromosomal deletion, SNP nonsense mutation, gene deletion, is expected to lead to “to deficits in myelination” as taught above.
Since both claim sets teach administering sobetirome or prodrugs thereof for the treatment of diseases associated with dysmyelination, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Scanlan.
3. Claims 1-10, 14-16, and 18-22 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-11 of U.S. Patent No. 11104654 (hereinafter referred to as Scanlan).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a sobetirome and prodrugs thereof for the treatment of dysmyelinating diseases.
Scanlan teaches a sobetirome prodrug (Claim 1). The prodrug is used in treating X-linked ALD, a dysmyelinating disease (Col 2, Lines 64+).
Scanlan fails to teach co-administration with pro-myelinating agents or muscarinic receptor antagonists, specific treatment of PTHS, and TCF4 mutation in PTHS.
Regarding Claims 14-16 and 18-19, Hartley teaches a method of treating X-linked adrenoleukodystrophy, a neurodevelopmental disorder, comprising administering sobetirome (Claims 1-7). Sobetirome is administered via the claimed routes once or multiple times daily (Page 16). Hartley teaches remyelination comprises administering T3 (Page 1). Remyelination with sobetirome in diseases with insufficient myelination or underdeveloped myelin sheaths is contemplated too (Page 2, Lines 1-11). Diseases include X-linked ALD, adult Refsum disease, and Krabbe disease (Claims 1-7). Therefore, one of skill in the art seeking to treat diseases associated with dysmyelination or insufficient myelination would administer T3 with sobetirome as suggested by Hartley and expect success in recovering myelin sheath function because both T3 and sobetirome are taught to be use for this purpose. Further, in a related disease, multiple sclerosis, both agents are administered to reverse demyelination and promote remyelination of healthy sheaths (Page 24).
Abiraman teaches “[u]sing solifenacin, an FDA-approved drug, we show that adjunct therapy increased the rate of myelination” and “[s]olifenacin promotes hOPC differentiation and myelination” (Pages 3676 and 3684).
In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” See MPEP 2144.06. The compounds of Scanlan, Hartley, and Abiraman are all directed toward the healthy remyelination of insufficiently myelinated or dysmyelinated sheaths. Therefore, it is prima facie obvious to form a composition comprising the examined compound, T3, and solfenacin to promote healthy myelination in diseases described in Scanlan and Hartley associated with dysmyelination. One of skill in the art would expect success in treating the diseases with both agents because insufficient myelination is corrected by sobetirome, T3, and solifenacin.
Phan teaches “reduced myelination in the PTHS mouse model was due directly to Tcf4 mutation” and “defects in myelination are a primary pathophysiology in PTHS” (Pages 383-384). Further, “Tcf4 mutation leads to deficits in myelination” (Page 376).
One of ordinary skill in the art seeking to treat PTHS and symptoms resulting therefrom as described in examined Claim 5, informed by Scanlan teaching sobetirome promotes healthy myelination in diseases associated with de- or dysmyelination and Phan teaching PTHS’s primary pathophysiology is related to myelination defects, would seek to use sobetirome to correct the dysmyelination experienced by those afflicted by PTHS. The same artisan would expect success in doing so because of the related pathologies of the specific diseases described in Scanlan, Hartley, and Phan as well as sobetirome’s known therapeutic uses in promoting healthy myelination of axon sheaths before the effective filing date of the examined claims.
Regarding Claims 6-10, one of skill in the art would expect success in treating any one of the TCF4 mutant subpopulations because disruption of TCF4, whether through chromosomal deletion, SNP nonsense mutation, gene deletion, is expected to lead to “to deficits in myelination” as taught above.
Since both claim sets teach administering sobetirome or prodrugs thereof for the treatment of diseases associated with dysmyelination, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Scanlan.
4. Claims 1-14 and 17-22 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-11 of U.S. Patent No. 11325886 (hereinafter referred to as Scanlan).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a sobetirome and prodrugs thereof for the treatment of dysmyelinating diseases.
Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Scanlan teaches sobetirome prodrug Sob-AM2:
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(Claim 12). The prodrug is used in treating X-linked ALD or adult Refsum disease, dysmyelinating diseases (Col 13-14). Adult Refsum disease has onset in childhood or adolescence (Col 23, Lines 14-24). Routes of administration include oral, intravenous, and others (Col 16, Lines 5-11).
Scanlan fails to teach co-administration with pro-myelinating agents or muscarinic receptor antagonists, specific treatment of PTHS, and TCF4 mutation in PTHS.
Regarding Claims 18-19, Hartley teaches remyelination comprises administering T3 (Page 1). Remyelination with sobetirome in diseases with insufficient myelination or underdeveloped myelin sheaths is contemplated too (Page 2, Lines 1-11). Diseases include X-linked ALD, adult Refsum disease, and Krabbe disease (Claims 1-7). Therefore, one of skill in the art seeking to treat diseases associated with dysmyelination or insufficient myelination would administer T3 with sobetirome as suggested by Hartley and expect success in recovering myelin sheath function because both T3 and sobetirome are taught to be use for this purpose. Further, in a related disease, multiple sclerosis, both agents are administered to reverse demyelination and promote remyelination of healthy sheaths (Page 24).
Abiraman teaches “[u]sing solifenacin, an FDA-approved drug, we show that adjunct therapy increased the rate of myelination” and “[s]olifenacin promotes hOPC differentiation and myelination” (Pages 3676 and 3684).
In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” See MPEP 2144.06. The compounds of Scanlan, Hartley, and Abiraman are all directed toward the healthy remyelination of insufficiently myelinated or dysmyelinated sheaths. Therefore, it is prima facie obvious to form a composition comprising the examined compound, T3, and solfenacin to promote healthy myelination in diseases described in Scanlan and Hartley associated with dysmyelination. One of skill in the art would expect success in treating the diseases with both agents because insufficient myelination is corrected by sobetirome, T3, and solifenacin.
Phan teaches “reduced myelination in the PTHS mouse model was due directly to Tcf4 mutation” and “defects in myelination are a primary pathophysiology in PTHS” (Pages 383-384). Further, “Tcf4 mutation leads to deficits in myelination” (Page 376).
One of ordinary skill in the art seeking to treat PTHS and symptoms resulting therefrom as described in examined Claim 5, informed by Scanlan teaching sobetirome promotes healthy myelination in diseases associated with de- or dysmyelination and Phan teaching PTHS’s primary pathophysiology is related to myelination defects, would seek to use sobetirome to correct the dysmyelination experienced by those afflicted by PTHS. The same artisan would expect success in doing so because of the related pathologies of the specific diseases described in Scanlan, Hartley, and Phan as well as sobetirome’s known therapeutic uses in promoting healthy myelination of axon sheaths before the effective filing date of the examined claims.
Regarding Claims 6-10, one of skill in the art would expect success in treating any one of the TCF4 mutant subpopulations because disruption of TCF4, whether through chromosomal deletion, SNP nonsense mutation, gene deletion, is expected to lead to “to deficits in myelination” as taught above.
Since both claim sets teach administering sobetirome or prodrugs thereof for the treatment of diseases associated with dysmyelination, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Scanlan.
Conclusion
No claim is allowable.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627