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 .
Election/Restrictions
2. Applicant’s election of Group I, claims 1, 2, 4-16 and 21, and species elections of (i) the retinoid of formula I: tazarotene, (ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)-nicotinate), and (ii) multiple sulfatase deficiency, in the reply filed on December 4, 2025, is acknowledged with appreciation. Claims 1, 2, 4-6, 13-16 and 21 are readable on the elected species.
2. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
3. Accordingly, claims 7-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim.
4. Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
5. Claims 1, 2, 4-6, 13-16 and 21 are under examination with the elected species and are the subject of this office action.
Claim Rejections - 35 USC § 112(b)
6. 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.
7. Claim 1, 2, 4-6, 13-16 and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
8. Claims 1, 4, 13-16 and 21 are unclear regarding the recitation of a method for the treatment of plural “individuals” in the preamble of each claim, yet independent claim 1 recites administering at least one retinoid to a single individual in the body of the claim, i.e., “to said individual” (emphasis added). If Applicant intends to recite a method of treating a single individual, the singular term “individual” should be used, rather than plural “individuals.”
9. Claims 2, 5, and 6, are rejected as being dependent upon and including all of the limitations of claim 1.
Appropriate correction is requested.
In view of a broadest reasonable interpretation, the recitation of “treatment of individuals is construed to mean: “a method for the treatment of an individual…”.
10. Claim 2 is confusing because it recites that the administration of at least one retinoid is “periodically repeated,” however the term "periodically" is a relative term which renders the claim indefinite. The term “periodically” is not defined in the claim itself or in claim 1 (in the chain of dependency), the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Specification at page 8, second paragraph, describes examples of periodic repetition including daily, more than one time per day, weekly, monthly, or systemically by implant etc. In the Examples at pages 14 and 15, the Specification describes treating for periods of 3 days, 6 days, and 40 days.
Therefore, applying a broadest reasonable interpretation consistent with the Specification, the recitation of “periodically repeated” is construed to mean “repeated daily.”
11. Claim 21 is confusing in the following aspects:
(a) In line 1, claim 21 recites the limitation "the method for the treatment…” however claim 21 is independent so it is not clear what is intended by “the method.” There is insufficient antecedent basis for this limitation in the claim.
(b) In lines 3-4, claim 21 recites that the method of treatment is “with a pharmaceutical composition…” however this limitation is confusing as the claim does not comprise an active treatment/ administration step, such that it is unclear how the pharmaceutical composition is used.
(c) In lines 4-6, claim 21 recites the limitation: “at least one active agent is a compound of the general formulas I, II or III and the second retinoid based active compound is a compound of general formula I, II or III,” however it is not clear what is intended by the “at least one active agent” and “the second retinoid based active compound.” Claim 21 is independent (i.e., does not depend from a previous claim) and fails to define any of “general formulas I, II or III,” therefore one skilled in the art would not know what is embraced by an “active agent” or “retinoid based active compound,” such that the metes and bounds of the claim cannot be ascertained.
There is insufficient antecedent basis for these limitations in the claim. Claim 21 has not been further treated on the merits. In re Steele, 305 F.2d 859,134 USPQ 292 (CCPA 1962) (it is improper to rely on speculative assumptions regarding the meaning of a claim and then base a rejection under 35 U.S.C. 103 on these assumptions).
Claim Rejections - 35 USC § 112(a)
12. Claims 1, 2, 4-6, 13-16 and 21 are rejected under 35 USC 112(a), because the specification, while being enabling for a method of administering the elected compound species tazarotene and those embodied by the instant Specification for treating multiple sulfatase deficiency, is not considered enabled for a method of administering any/ all of the other compound species encompassed by “third-generation retinoid,” including any/all retinoid compounds of formulae I, II or a combination of a compound of formula I and a compound of formula II, for treating the full scope of disease associated with sulfatase deficiencies, as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
13. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below.
14. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.” In the instant case, the claimed invention pertains to a method of administering any third-generation retinoid (including any/ all compounds of formulae I, II, or a combination of formulae I and II), which are alleged by the Specification to increase arylsulfatase A activity, in order to treat the full scope of “diseases associated with sulfatase deficiencies.”
15. The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
16. As discussed above, the instantly claimed invention pertains a method of administering any third generation retinoid (including any/ all compounds of formulae I, II, or a combination of I and II), which are alleged by the Specification to increase arylsulfatase A activity, in order to treat diseases associated with sulfatase deficiencies.”
At the time the instant application was filed, it would have been known by those of ordinary skill in the art that - due in large part to the strict requirement of complementarity between a compound and its corresponding binding site on a target receptor or enzyme - compounds, in the vast majority of cases, demonstrate a remarkably high correlation between their structure, specificity and ability to produce a pharmacological effect. At the same time, it would have also been generally assumed that two compounds with similar chemical properties would exhibit similar biological effects. Thus, given a series of compounds that are shown to exert an activity of interest (or given a target of interest), the ordinarily skilled artisan would have expected that a limited genus of related compounds (e.g., compounds exhibiting near equal molecular shapes and volumes, approximately the same distribution of electrons, and similar physical properties such as hydrophobicity, etc) would interact with the given target to elicit a related biological response.
17. Accordingly, at the time the invention was made, the relative skill of those in the art tasked with identifying compounds exerting an activity of interest would have been high, as the ordinarily skilled artisan would have had, at minimum, a Ph.D. and experience with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods. Deciding which technique to use would have been determined by the skilled artisan’s knowledge regarding the compound and target of interest. Ligand based drug design relies on knowledge of a compound or compounds of interest (i.e., ligands) to derive new compounds that will, in theory, similarly interact with the target of interest to elicit the activity of interest. Conversely, structure based drug design relies on knowledge of the three dimensional structure of the target of interest (i.e., receptor, ion channel, or enzyme) to derive new compounds that will, in theory, interact with the target of interest to elicit the activity of interest. In either case, the compounds derived from these techniques (applied alone or in combination) are then subjected to in vitro testing for validation.
18. The state of the art regarding diseases caused by deficiencies of sulfatase activities is that said diseases encompass specific sulfatase and multiple sulfatase deficiencies, wherein specific sulfatase deficiencies include: Metachromatic Leukodystrophy (MLD), deficiency of Arylsulfatase A, causing severe neurological damage from sulfatide buildup; Mucopolysaccharidoses (MPS), several types (MPS II, IIIA, IIID, IVA, VI) involve sulfatase defects in GAG breakdown, leading to skeletal & organ issues; X-linked Ichthyosis: Steroid sulfatase (Arylsulfatase C) deficiency results in thick, scaly skin; Chondrodysplasia Punctata (Rhizomelic Type): Arylsulfatase E (ARSE) deficiency affects bone and cartilage development; and Maroteaux-Lamy Syndrome (MPS VI): Arylsulfatase B deficiency. In multiple sulfatase deficiency (MSD), which is caused by mutations in the SUMF1 gene, leading to the malfunction of all 17 human sulfatases, MSD combines features of several storage disorders, including neurological: developmental delay/regression, ataxia, seizures, autistic features, microcephaly/hydrocephalus, and spasticity; dermatological: dry, scaly skin (ichthyosis) and excess hair growth (hypertrichosis); skeletal: abnormalities, coarse facial features, vertebral issues; hearing loss, heart defects, and enlarged liver/spleen (hepatosplenomegaly).
19. The Level of Predictability in the Art: Once a compound has been identified by ligand based and/or structure-based drug design methods as potentially binding to the target molecule, it must be evaluated. However, as discussed by Anderson (Chem and Biol 10:787-797, 2003), “it is important to consider that the ranking assigned by the scoring function is not always indicative of a true binding constant, since the model of the target:ligand interaction is inherently an approximation. Usually, several molecules which scored well during the docking run are evaluated in further tests since even the top scoring molecule could fail in vitro assays… Finally, leads are brought into the wet lab for biochemical evaluation” (Anderson, page 794, Column 1). By that point, as noted by Thiel (Nature Biotechnol 2:513-519, 2004), “libraries are small and hit rates are on the order of one in ten” (Thiel, page 517, column 2). This low level of predictability is not surprising considering that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised. This is certainly true in the case of retinoids (including synthetic retinoids) which, as disclosed by Ferreira et al. (Nature Communications, 2020), demonstrate significantly altered activity following minor modifications:
“RA formulations have some limitations that preclude a more significant translation to the clinic. For example, ATRA, 9-cis-RA, and 13-cis-RA, which belong to the first generation of retinoids, are being gradually replaced in some applications by third-generation retinoids130. Although many of these formulations have been tested in preclinical models, the clinical translation is still relatively low. For example, although nanoparticles delivered systemically have been extensively explored in animal tests, clinical translation remains compromised because of delivery (e.g., limited efficacy in terms of cell targeting, limited capacity to cross biological barriers), technical (e.g., scale-up), and regulatory aspects (e.g., study design and approval challenges).”
(page 11, left column, first full paragraph).
20. And, Cosma et al. teach that diseases caused by deficiencies of sulfatase activities involve genetic mutations, implicating multiple systems including central and peripheral nervous systems, and therefore are complex and unpredictable to treat:
“Most of these conditions are lysosomal storage disorders in which phenotypic consequences depend on the type and tissue distribution of the stored material. Among them are five different types of mucopolysaccharidoses (MPS types II, IIIA, IIID, IVA, and VI) due to deficiencies of sulfatases acting in the catabolism of glycosaminoglycans (Neufeld and Muenzer, 2001) and metachromatic leukodystrophy (MLD), which is characterized by the storage of sulfolipids in the central and peripheral nervous systems leading to severe and progressive neurologic deterioration (Von Figura et al., 2001). In addition, two human diseases are caused by deficiencies of nonlysosomal sulfatases. These include X- linked ichthyosis, a skin disorder due to steroid sulfatase (STS/ARSC) deficiency (Ballabio and Shapiro, 2001), and chondrodysplasia punctata, a disorder affecting bone and cartilage due to arylsulfatase E (ARSE) deficiency (Franco et al., 1995). ARSE is also implicated in a drug-induced human malformation syndrome, Warfarin embryopathy, caused by inhibition of the enzymatic activity due to in utero exposure to warfarin during pregnancy (Franco et al., 1995).”
In an intriguing human monogenic disorder, multiple sulfatase deficiency (MSD), all sulfatase activities are simultaneously defective Austin 1966, Kolodny and Fluharty 1995, Hopwood and Ballabio 2001. Consequently, the phenotype of this severe multisystemic disease combines the features observed in individual sulfatase deficiencies. The posttranslational modification which is required for the activity of all sulfatases was found to be defective in a cell line from a patient with MSD, suggesting that this disorder is caused by a mutation in a gene, or genes, implicated in the cysteine-to-formylglycine conversion machinery (Schmidt et al., 1995). In spite of an intense biological and medical interest, efforts aimed at the identification of the MSD gene(s) have been hampered by the rarity of MSD patients and consequent lack of suitable familial cases to perform genetic mapping.”
(Page 445, right column, last paragraph-page 446, left column, first two paragraphs).
21. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification demonstrates the effects of just two third-generation retinoid compound species: tazarotene and bexarotene, on the activity of arylsulfatase A in MSD cells (see Examples on pages 13-15).
22. Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added).
23. At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
24. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims." Amgen, Inc, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation.”
25. As to the first inquiry, as discussed above, the claims are drawn to a method of administering any third-generation retinoid (including any/ all compounds of formulae I, II, or a combination of formulae I and II), which are alleged by the Specification to increase arylsulfatase A activity, in order to treat diseases associated with sulfatase deficiencies. Said diseases are multisystemic, complex and severe, and caused by deficiencies in 17 unique sulfatases, i.e.:
“at least eight human monogenic diseases caused by the deficiency of individual sulfatase activities (Hopwood and Ballabio, 2001). Most of these conditions are lysosomal storage disorders in which phenotypic consequences depend on the type and tissue distribution of the stored material. Among them are five different types of mucopolysaccharidoses (MPS types II, IIIA, IIID, IVA, and VI) due to deficiencies of sulfatases acting in the catabolism of glycosaminoglycans (Neufeld and Muenzer, 2001) and metachromatic leukodystrophy (MLD), which is characterized by the storage of sulfolipids in the central and peripheral nervous systems leading to severe and progressive neurologic deterioration (Von Figura et al., 2001). In addition, two human diseases are caused by deficiencies of nonlysosomal sulfatases. These include X-linked ichthyosis, a skin disorder due to steroid sulfatase (STS/ARSC) deficiency (Ballabio and Shapiro, 2001), and chondrodysplasia punctata, a disorder affecting bone and cartilage due to arylsulfatase E (ARSE) deficiency (Franco et al., 1995). ARSE is also implicated in a drug-induced human malformation syndrome, Warfarin embryopathy, caused by inhibition of the enzymatic activity due to in utero exposure to warfarin during pregnancy (Franco et al., 1995).
In an intriguing human monogenic disorder, multiple sulfatase deficiency (MSD), all sulfatase activities are simultaneously defective Austin 1966, Kolodny and Fluharty 1995, Hopwood and Ballabio 2001. Consequently, the phenotype of this severe multisystemic disease combines the features observed in individual sulfatase deficiencies.”
(Cosma et al., page 445, right column, last paragraph – page 446, left column, first two paragraphs), which embraces a broad scope of diseases caused by deficiencies in sulfatase activity, as well as any/ all diseases “associated with” sulfatase deficiencies which encompass a vast spectrum of morbidity and pathogenic associations. Thus, considering that the scope of “third-generation retinoids” (which includes the genus of formula I and/or formula II), encompasses hundreds of millions of compound species, and potentially billions of retinoid compound species, and that diseases associated with sulfatase deficiencies are multisystemic and complex, it is evident that the claims are broad.
27. Yet, as discussed above, the instant Specification demonstrates the activity of only two third-generation compound species encompassed by formulae I and/or II as recited by the claims, for treating one disease, multiple sulfatase deficiency. As such, the claims are extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
28. Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to any third-generation retinoid (including any/ all compounds of formulae I, II, or a combination of formulae I and II), which are alleged by the Specification to increase arylsulfatase A activity in MSD cells. Since identifying any compound which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of “third-generation retinoid” (including any/ all compounds of formulae I, II, or a combination of formulae I and II) with respect to the disclosure since Formula (I) encompasses hundreds of millions of compound species, and potentially billions of compound species, whereas the instant Specification discloses only 2 such compound species exerting the disclosed activity. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan (armed with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods) could not reasonably predict which of the hundreds of millions of compounds encompassed by “third-generation retinoids” (including any/ all compounds of formulae I, II, or a combination of formulae I and II) would exert the alleged activity based on the limited disclosure of two active compounds. Although the skilled artisan would have known that certain chemical modifications to the disclosed compounds may predictably provide structurally related compounds having similarly activity, the skilled artisan would have also known that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, as evidenced by Ferreira et al, third generation retinoids can demonstrate significant limitations and unpredictability since even minor modifications result in drastic changes in activity. Thus, in order to identify usable retinoids, the skilled artisan (at minimum) would have to carry out ligand-based drug design methods using the two disclosed compounds as a starting point and, assuming the structure of the target receptor was known, combine the findings with data derived from structure-based drug design methods to arrive at a small library of “lead” compounds believed to possess the activity of interest. The skilled artisan would then synthesize lead compounds that are within the scope of formula I and/or formula II for in vitro testing. At this point, however, even "the top scoring molecule could fail in vitro assays” (Anderson page 794, column 1) and “hit rates are on the order of one in ten” (Thiel, page 517, column 2). Given the limitations and unpredictability of retinoids in particular, as evidenced by Ferreira et al, it is highly unpredictable whether any compound within the subgenus of compounds of formula I and/or formula II identified by rational drug design based on the instant disclosure would, in fact, be usable. Whether the other compounds of formula I and/or formula II (i.e., those not identified by rational drug design based on the instant disclosure) would be usable is even less predictable. As such, the only way to ascertain which of the hundreds of millions, and potentially billions, of claimed compounds encompassed by “at least one retinoid” or “formula I” and/or “formula II” are usable to treat any disease associated with sulfatase deficiencies, based on the limited disclosure, would require undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure, i.e. limit the scope of “a retinoid of the third-generation” and limit the scope of “diseases associated with sulfatase deficiencies.”
Claim Rejections - 35 USC § 102
28. Claims 1, 2, 4-6, and 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vahlquist et al., Acta Derm Venereol 2008, as evidenced by the webpage printout of https://medlineplus.gov/genetics/condition/multiple-sulfatase-deficiency/ (last updated May 17, 2021).
Claim 1 is drawn to a method of treatment of individuals suffering from diseases associated with sulfatase deficiencies, (more specifically a multiple sulfatase deficiency (claim 13)), comprising the step of administering at least once (more specifically periodic repetition (claim 2)), a therapeutically effective amount of at least one retinoid that is a retinoid of the third generation, (more specifically tazarotene, (ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)- nicotinate, (claims 6 and 14). Claims 4 and 5 embrace the retinoid tazarotene.
Claim 15 is drawn to claim 1, wherein at least two retinoids are administered.
In view of a broadest reasonable interpretation of claim 1, the recitation of “treatment of individuals” is construed to mean “the treatment of an individual.”
In view of a broadest reasonable interpretation of claim 2, the recitation of “periodically repeated” is construed to mean “daily administration.”
29. Vahlquist et al. teach the treatment of congenital Ichthyosis (i.e., non-bullous, non-syndromic, autosomal recessive congenital ichthyosis), comprising daily topical application of the retinoid tazarotene in combination with the retinoids acitretin or isotretinoin (see Table VI at page 9). Vahlquist et al. discuss the advantages of employing aromatic retinoids:
“[i]t is amazing that ichthyoses with such a broad spectrum of diverse aetiologies can respond to the same few systemic retinoid drugs. While the spectrum of efficacy and toxicity of different retinoids are similar and overlap, they are not identical. In different clinical situations there may be advantages of one retinoid over another. In the case of LI, both isotretinoin and the aromatic retinoids (etretinate, acitretin) have been found to be efficacious (46–48). The aromatic retinoids have a relatively greater effect on volar skin leading to an advantage in the treatment of palmoplantar hyperkeratosis”
(see the first full paragraph on page 10, left column).
30. And, it is clear as evidenced by Medline Plus that ichthyosis is manifested in all three types of Multiple sulfatase deficiency, such that an individual suffering from a multiple sulfatase deficiency meets the limitation of an individual in need thereof (Page 1, paragraphs 2-4).
Claim Rejections - 35 USC § 103
31. 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.
32. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
33. Claims 16 is rejected under 35 U.S.C. 103 as being unpatentable over Vahlquist et al, Acta Derm Venereol 2008, as evidenced by the webpage printout of https://medlineplus.gov/genetics/condition/multiple-sulfatase-deficiency/ (last updated May 17, 2021), as applied to claims 1, 2, 4-6, and 13-15 above, and further in view of Azulay, Retinoids 2016.
Claims 1 and 15 are addressed in detail in the 35 USC 102(a)(1) rejection, above.
Claim 16 is drawn to claim 15, wherein the retinoids are selected from tazarotene, bexarotene and palvarotene.
34. Vahlquist et al. teach the treatment of an individual suffering from congenital Ichthyosis, which manifests in all three types of multiple sulfatase deficiency, comprising the topical application of the retinoid tazarotene in an individual in need thereof, but do not teach combined administration with bexarotene or palvarotene.
35. Yet, Azulay et al teach that tazarotene and bexarotene are both third generation aromatic retinoids: “the third generation is represented by bexarotene, adapalene, tazarotene, motretinide, and arotinoides. They are polyaromatic retinoids resulting from the cyclization of the polyenic side chain,” (see at page 4, first paragraph under “Third generation”). And, Vahlquist et al. suggest that the spectrum of efficacy of different retinoids are similar and overlap, (see the 35 U.S.C. 102(a)(1) rejection above).
36. Therefore, one of skill in the art before the effective filing date of the claimed invention would have been motivated to administer bexarotene with tazarotene for treating an individual suffering from multiple sulfatase deficiency (characterized by ichthyosis), with a reasonable expectation of success. And, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law, please see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings). Furthermore, MPEP 2144 teaches that the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination.
37. In the instant case, two known third generation retinoid compounds which individually demonstrate retinoid action could be combined in order to achieve an additive effect for increasing sulfatase activity, with the expected result of a composition suitable for the treatment of an individual with Ichthyosis, present in all three types of multiple sulfatase deficiency.
Please refer to MPEP 2144.06 “I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE” wherein Kerkhoven is specifically referenced:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
As stated by the Court in KSR International Co., v. Teleflex Inc., 127 US 1727 (2007), “when a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious” (quoting Sakraida v. AG Pro, Inc., 425 US 273 (1976); see also: Merck v. Biocraft (874 F.2d 804, 807 (Fed. Cir. 1989), indicating that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands; Sundance, Inc. v. DeMonte Fabricated, Ltd., 550 F.3d 1356 (Fed. Cir. 2008): a claimed invention is obvious is it is a combination of known prior art elements that would reasonably have been expected to maintain their respective properties or functions after they had been combined; Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945): indicating that “[r]eading a list and selecting a known component to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle”.
As such, a prima facie case of obviousness is established.
Double Patenting
38. 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).
39. 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).
40. 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.
41. 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.
42. Claims 1, 2, 4-6 and 13-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,696,897. Although the claims at issue are not identical, they are not patentably distinct from each other because Applicant’s instant claims recite:
Claim 1 is drawn to a method of treatment of individuals suffering from diseases associated with sulfatase deficiencies, (more specifically a multiple sulfatase deficiency (claim 13)), comprising the step of administering at least once (more specifically periodic repetition (claim 2)), a therapeutically effective amount of at least one retinoid that is a retinoid of the third generation, (more specifically tazarotene, (ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)- nicotinate, (claims 6 and 14). Claims 4 and 5 embrace the retinoid tazarotene.
Claim 15 is drawn to claim 1, wherein at least two retinoids are administered. Claim 16 is drawn to claim 15, wherein the retinoids are selected from tazarotene, bexarotene and palvarotene.
42. Claims 1-6 of U.S. Pat. No. 11,696,897 B2 recite the following :
PNG
media_image1.png
386
368
media_image1.png
Greyscale
PNG
media_image2.png
491
743
media_image2.png
Greyscale
43. Thus, the instantly recited method of treating an individual suffering from a multiple sulfatase deficiency comprising administering the third generation retinoid tazarotene to said individual is fully embraced by the claims of U.S. Pat. No. 11,696,897 B2. Claim 1 of U.S. Pat. No. 11,696,897 also embraces administering the combination of tazarotene and bexarotene. Claim 2 of U.S. Pat. No. 11,696,897 recites daily administration. As such, it would have been obvious to one skilled in the art to practice the known method of administering the third generation retinoid tazarotene to an individual suffering from a multiple sulfatase deficiency, with a reasonable expectation of success.
Thus claims 1, 2, 4-6 and 13-16 are prima facie obvious over claims 1-6 of U.S. Patent No. 11,696,897.
Conclusion
44. Claims 1, 2, 4-16 and 21 are present in the application, and claims 7-12 are presently withdrawn from consideration. 1, 2, 4-6, 13-16 and 21 are rejected. No claim is presently allowable.
45. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached on Monday-Friday 8:30AM-5PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JANET L COPPINS/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628