DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-18 are pending.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/US2022/033159, filed on June 11, 2022. This application also claims the benefits of foreign priority to CN202110653751.3, filed on June 11, 2021 and CN202210187387.0, filed on February 28, 2022.
Specification - Abstract
The abstract of the disclosure is objected to because it is not in compliance with 37 C.F.R. 1.72 (b). Specifically, the sheet presenting the abstract includes other parts of the application or other material. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The inclusion of instant Formula (I) in the abstract is appropriate and may be retained in the revised abstract.
Additionally, instead of reciting “phosphonate-containing heterocycle compounds,” the abstract should read “phosphine oxide-containing heterocycle compounds.” This is because “phosphonate” refers to the following group:
PNG
media_image1.png
201
242
media_image1.png
Greyscale
whereas “phosphine oxide” refers to the following group:
PNG
media_image2.png
200
225
media_image2.png
Greyscale
The latter structure more closely resembles the general structure of the instant compound.
Appropriate correction is required.
Specification - Disclosure
The 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 Objections
Claims 1, 4, 6, 7, 9, and 17 are objected to because of the following informalities:
In claims 1 and 9:
“R1 is C1-6 alkyl… wherein C1-6 alkyl… and C3-6 cycloalkyl)” should read“R1 is C1-6 alkyl… wherein C1-6 alkyl… and C3-6 cycloalkyl” [i.e., “)” after “C3-6 cycloalkyl” is removed”]
In claims 4 and 7:
“claims 1” should read “claim 1”
In claim 6:
There are two moiety B that are the same and listed side-by-side:
PNG
media_image3.png
72
164
media_image3.png
Greyscale
(see claims document, pg. 11, 1st row, 2nd and 3rd moiety B)
One of them may be removed.
Further in claim 7:
The last word of the claim (“, substituted”) can be removed.
In claim 17:
The set of “wherein” clauses defining the various diseases or disorders is recited twice.
For example:
the “wherein the autoimmune disease or inflammation disease is…” block appears on pg. 29 and 30 of the claim set,
the “wherein the enteritis is…” block appears on pg. 29 and 30 of the claim set,
the “wherein the skin disease is…” block appears on pg. 29 and 31 of the claim set
and so on
The claim must be amended to delete the repeated language.
Appropriate correction is required.
As there are a number of claim objections identified, Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification
Claim 18 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. See the “Claim Rejections - 35 USC § 112(d)” section below for details. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Examiner’s note on novelty and nonobviousness
The closest prior art is:
Gao et al. (Gao) (WO2020156311A1; published August 6, 2020).
Novelty:
Gao teaches pyridazine derivative inhibitors of formula (I) (herein, referred to as Gao-formula-I):
PNG
media_image4.png
375
287
media_image4.png
Greyscale
(see Gao, abstract)
as compounds capable of inhibiting TYK2 activity. The variables of Gao-formula-I are defined in claim 1 of Gao (note: the triazole group corresponds to “ring A” of instant formula (I)). The TYK2 inhibitors represented by Gao-formula-I differ from those presently claimed in that all the compounds disclosed in Gao do not comprise a phosphine oxide moiety that is bonded to the triazole moiety (which corresponds to “ring A” of instant formula (I)).
Thus, the instant invention is considered novel.
Nonobviousness:
Both Gao and the present invention disclose TYK2 inhibitors. An example of a compound disclosed by Gao is compound 64 (herein, referred to as Gao-compound-64) which has the following structure (pg. 64 of original Chinese document provided by Applicant):
PNG
media_image5.png
300
312
media_image5.png
Greyscale
.
If Gao-compound-64 was modified to include a phosphine oxide moiety bonded to the triazole ring, the resulting compound would fall within the scope of instant claim 1. However, Gao neither teaches nor suggests this structure modification, nor does Gao provide any teaching or suggestion that such a modification would improve inhibition of TYK2 activity in cells.
Thus, the instant invention is considered nonobvious.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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 1-13 and 15-18 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:
A compound of Formula (I):
PNG
media_image6.png
302
209
media_image6.png
Greyscale
or a pharmaceutically acceptable salt, solvate, isotope-labeled derivative, or isomer thereof, wherein:
n is 0, 1, 2, or 3
X1 is N or CH
each of X2, X3, and X4 is independently CH, C-halide, or N
ring A is phenyl, 5- or 6-membered heteroaryl
R1 = C1-6 alkyl, -NH(deuterated C1-6 alkyl), or -NH(C1-6 alkyl)
wherein C1-6 alkyl is unsubstituted
R2 =
PNG
media_image7.png
114
171
media_image7.png
Greyscale
R3 = H, halide, CN, unsubstituted C1-6 alkyl, or unsubstituted -O(C1-6 alkyl)
R4 = H, unsubstituted C1-6 alkyl, C1-6 alkyl substituted with deuterium, or unsubstituted C3-6 cycloalkyl
each of R5 and R6 is independently unsubstituted C1-6 alkyl or unsubstituted C3-6 cycloalkyl or
R5 and R6, together with P attached thereto, form an unsubstituted 5-6 membered heterocycloalkyl
R7 = H; and
A method for treating a disease or disorder by inhibiting TYK2 mediated signal transduction in a subject suffering therefrom, comprising administering to the subject a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt, solvate, isotope-labeled derivative, or isomer thereof, wherein the disease or disorder is psoriasis;
does not reasonably provide enablement for elements that are outside the scope of the enabling elements listed above. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
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, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims phosphine oxide-containing heterocycle compounds with TYK2 kinase inhibitory activity, pharmaceutical compositions comprising the same, and applications thereof. The present disclosure provides compounds of Formula (I), as inhibitors of TYK2 kinase. These compounds can be used for treating TYK2 kinase-related diseases and/or conditions.
Formula (I) is provided and its variables are defined in instant claim 1.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in medicinal chemistry and organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
State of the prior art
Regarding the structure of the instant compounds:
See the “Examiner’s note on novelty and nonobviousness” section above.
Regarding typical animal models used for the in vivo study of specific diseases:
Collagen-induced arthritis (CIA) is an established experimental model of human rheumatoid arthritis induced by immunization of mice with bovine or chicken type II collagen emulsified in complete Freund’s adjuvant (CFA) that results in rheumatic symptoms such as joint inflammation and swelling.
Richter, J. et al. Clinical and Experimental Immunology 2014, 177, 121-133.; pg. 122, left col., 2nd paragraph, 1st sentence.
Xenograft models are generated by implanting human cancer cells into immune-deficient mice and are widely used to evaluate the efficacy and toxicity of candidate anticancer agents.
Jung, J. Toxicol. Res. 2014, 30, pg. 1-5; pg. 1, introduction.
The presence or absence of working examples; the amount of direction or guidance present; and quantity of experimentation necessary
Part I:
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
Even though the instant specification provides, for example, data regarding inhibition of TYK2 activity in cells by compounds of varying structures (see Table 3 of instant specification on pg. 92-94), the disclosure does not include any data on the TYK2 inhibitory activity of compounds of instant Formula I with structural elements that are outside the scope of the enabling elements listed above. For example, there are no working examples of a compound of instant Formula I wherein:
R1 is a C3-6 cycloalkyl or
R2 is an aryl, heteroaryl, or heterocycloalkyl or
R7 is any of the substituents listed in instant claim 1 except for H.
Thus, the specification is not adequately reflecting the structural diversity of the claimed genus.
In the absence of clear guidance, a person of ordinary skill in the art would require undue experimentation to:
make all compounds comprising structural elements that are outside the scope of the enabling elements listed above and
determine which of those compounds are TYK2 inhibitors.
Part 2:
The instant specification discloses pharmacokinetic evaluation of the claimed compounds in mice, rats, and beagle dogs (see Example 23). The instant specification further provides an in vivo efficacy study for a single compound (i.e., instant compound B41) in an IL-23 induced psoriasis model.
However, instant claim 17 encompasses methods of treating a broad range of distinct diseases and disorders, including rheumatoid arthritis and various cancers. The specification does not provide experimental data demonstrating efficacy of the claimed compounds in established in vivo models relevant to these conditions. For example, as stated above, evaluation of a compound’s therapeutic efficacy in rheumatoid arthritis is commonly assessed using CIA models while a compound’s antitumor efficacy is typically evaluated using xenograft tumor models. The present application does not disclose testing of the claimed compounds in such models, nor does it provide sufficient guidance enabling treatment of these distinct disease states.
Evaluating the therapeutic efficacy of the instantly claimed compounds in established in vivo models appropriate for each of the numerous diseases recited in instant claim 17 would require extensive additional experimentation beyond that disclosed in the specification.
Thus, while the specification may enable treatment of psoriasis based on the working example provided (i.e., Example 24), it does not enable the full scope of the claimed methods encompassing the wide range of autoimmune, oncologic, and other diseases recited in instant claim 17.
The breadth of the claims
The claims are broad insofar as the instant claims recite a compound of general formula (I) wherein the compound can possess a structurally diverse range of chemical groups. Further, the instant claims recite a method of treating an extensive range of disease categories (see instant claim 17), each of which comprises numerous distinct disease entities.
Claims 2-13 and 15-18, which are dependent on claim 1, are also rejected for further requiring and/or reciting elements that are outside the scope of the enabling elements listed above.
Claim Rejections - 35 USC § 112(a) – Enablement
Claims 1-18 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
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, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
See the “1. The nature of the invention” subsection of the “Claim Rejections - 35 USC § 112(a) – Scope of Enablement” section above.
The level of the skill in the art
See the “2. The level of the skill in the art” subsection of the “Claim Rejections - 35 USC § 112(a) – Scope of Enablement” section above.
State of the prior art
See the “3. State of the prior art” subsection of the “Claim Rejections - 35 USC § 112(a) – Scope of Enablement” section above.
The presence or absence of working examples; the amount of direction or guidance present; and the quantity of experimentation necessary
The quantity of experimentation needed to make or use the invention must be considered to determine if undue experimentation is present. With regard to quantity of experimentation needed, (note Wolff et. al., "Burger's Medicinal Chemistry and Drug Discovery," 5th Ed. Part 1, pp. 975-977 (1995) provided with this action), which emphasizes the many experimental factors for consideration for a successful prodrug as well as the difficulty in extrapolating data from one species to another. See p.975-977. “Extensive development must be undertaken to find the correct chemical modification for a specific drug. Additionally, once a prodrug is formed, it is a new drug entity and therefore requires extensive and costly studies to determine safety and efficacy.” Banker, et. al., (1996), Modern Pharmaceutics, p.596, section “B. Prodrugs”, last paragraph. In view of all these factors undue experimentation would be required to practice the invention.
The scope of prodrugs is not adequately enabled or defined. Applicants provide no guidance as how the compounds are made more active in vivo nor do they provide any working examples of suitable prodrugs. The choice of a prodrug will vary from drug to drug. Therefore, more than minimal routine experimentation would be required to determine which ester, for instance, will be suitable for the instant invention. The application does not provide any guidance for one skilled in the art on how the prodrug is converted to active compounds, by what mechanisms and at what site the prodrug will be activated, what in vivo enzymes are likely involved in cleaving the protected group, etc.
Applicants provide no reasonable assurance that any and all known prodrugs will have the ability to regenerate in vivo to the instant compounds by one or more biological processes. It is not the norm that one can predict with any degree of accuracy a particular prodrug form of an active compound will be more soluble, more easily handled in formulations or more bioavailable without actual testing in vivo. Pursuant to In re Wands, 8 USPQ2d 1400, factors such as direction or guidance are not seen in the specification.
Many functional groups (e.g., hydroxy, amino groups) present in drugs are capable at least in theory to being derivatized but determining what is a prodrug and what is not requires knowledge of an intended effect (i.e. modification of an undesirable property in the parent drug- poor solubility, poor bioavailability, poor shelf-life) which is never identified by the specification.
The breadth of the claims
See the “5. The breadth of the claims” subsection of the “Claim Rejections - 35 USC § 112(a) – Scope of Enablement” section above.
Claim 16, which is dependent on claim 1, is also rejected for further requiring and/or reciting the non-enabling element (i.e., “prodrug” and “ester”) as discussed above.
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 1-18 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.
Claims 1-15, 17, and 18 recite “prodrug” and “ester.” The terms “prodrug” and “ester” render claims 1-15, 17, and 18 indefinite as a prodrug and an ester are general terms that do not have a defined structure known in the art. For example, one would not be apprised of the pharmacologically inactive form of the claimed compound from the simple recitation of “prodrug” or “ester” as the compound itself has multiple sites to which a prodrug or ester moiety could bind. Moreover, one could not ascertain as to which prodrug or ester moieties are within the scope of the claim, resulting in millions of combinations of prodrug and ester moieties associated with the claimed compound at different locations on its structure. One could not possibly envisage all the possibilities of a prodrug or ester of any compound of the instant invention.
Claim 16, which is dependent on claim 1, is also rejected for further requiring and/or reciting the indefinite limitation of claim 1.
Regarding claims 1, 3, and 9, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 17 and 18, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 2 recites the limitation "substituted or unsubstituted 5-10 membered heteroaryl" on pg. 5, line 2 of the claim set. Note: this limitation is not defining R2. Instead, this limitation is what R2 could be substituted with. Claim 2 is dependent on claim 1 which does not recite that R2 can further be substituted with a substituted or unsubstituted 5-10 membered heteroaryl. Thus, there is insufficient antecedent basis for this limitation in the claim.
Claims 6 and 11 recite the limitation “wherein the moiety B [as recited in claim 6 or moiety D as recited in claim 11] is selected from the group consisting of: …
PNG
media_image8.png
98
215
media_image8.png
Greyscale
…
PNG
media_image9.png
133
240
media_image9.png
Greyscale
PNG
media_image10.png
146
119
media_image10.png
Greyscale
…
PNG
media_image11.png
97
155
media_image11.png
Greyscale
…
PNG
media_image12.png
144
220
media_image12.png
Greyscale
…
PNG
media_image13.png
74
211
media_image13.png
Greyscale
…
PNG
media_image14.png
127
165
media_image14.png
Greyscale
…”
Regarding
PNG
media_image8.png
98
215
media_image8.png
Greyscale
PNG
media_image9.png
133
240
media_image9.png
Greyscale
and
PNG
media_image10.png
146
119
media_image10.png
Greyscale
”
Claims 6 and 11 are dependent on claims 4 and 9, respectively, which states that R2 can be any of the listed substituents, wherein, specifically, alkyl, deuterated alkyl, halo-alkyl, alkoxy, halo-alkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with one or more groups independently selected from the list of substituents recited in claims 4 or 9. Claims 4 or 9 never recites that R2 (i.e., referred to as moiety B in claim 6 and moiety D in claim 11) can be an imine group. Thus, there is insufficient antecedent basis for this limitation in claims 6 and 11.
Regarding
PNG
media_image11.png
97
155
media_image11.png
Greyscale
:
Claims 6 and 11 are dependent on claims 4 and 9, respectively, which recites that R2 can be a heterocycloalkyl that is substituted with one or more groups including C1-3 alkyl. Claims 4 and 9 never state that the substituent, C1-3 alkyl, can be further substituted with a cycloalkyl group. Thus, there is insufficient antecedent basis for this limitation in claims 6 and 11.
Regarding
PNG
media_image12.png
144
220
media_image12.png
Greyscale
,
PNG
media_image13.png
74
211
media_image13.png
Greyscale
, and
PNG
media_image14.png
127
165
media_image14.png
Greyscale
:
Claims 6 and 11 are dependent on claims 4 and 9, respectively, which recites that R2 can be -NRbRc wherein Rb is H and Rc is a heteroaryl (e.g., a pyridyl) that is substituted with a halide (e.g., F) and a C1-3 alkyl group (as recited in claim 4 or C1-6 alkyl group as recited in claim 9) (e.g., isopropyl). However, claims 4 and 9 never state that when the heteroaryl is substituted with a C1-3 alkyl group, the alkyl substituent can further be substituted with an -OH group. Thus, there is insufficient antecedent basis for this limitation in claims 6 and 11. As such, since substituents like an alkyl group cannot be further substituted, there is also an insufficient antecedent basis for the following limitation from claims 6 and 11:
“wherein, if present, each R11 is independently hydrogen, deuterium, halide, amino, -NO2, -CN, -OH, C1-3 alkyl, or C1-3 alkoxy”
which allows substituents like an alkyl group be further substituted by a R11 group.
Based on the claim language of claims 6 and 11 (i.e., which allows groups to be substituted with substituents wherein the substituent can be further substituted by R11), Examiner interprets claim 5 to mean that moiety A can have an R4 that can be further substituted with a R10. This means if R4 is a C1-6 alkyl group, it can be substituted with a R10 wherein R10 = C1-3 alkoxy. However, R4 being an alkyl-alkoxy group is not encompassed by claim 4 (i.e., the claim in which claim 5 is dependent upon). Thus, there is insufficient antecedent basis for this limitation in the claim.
Examiner also interprets claim 5 to mean that moiety A can be substituted with R10 at any position. However, a compound wherein the methyl groups (i.e., the groups bonded to P) being substituted with R10 = C1-3 alkoxy is not encompassed by claim 4. Thus, there is also an insufficient antecedent basis for this limitation in claim 5.
Based on the claim language of claims 6 and 11, Examiner interprets claim 10 to mean that moiety C as a whole can be substituted with 0 to 3 R10. This means, according to claim 10, the cyclopropyl groups bonded to P(=O) can be substituted with C1-3 alkoxy. However, R5 or R6 being a cyclopropyl-alkoxy group is not encompassed by instant claim 9 (i.e., the claim in which claim 10 is dependent upon). Thus, there is insufficient antecedent basis for this limitation in the claim.
Claim 18 is directed towards the compound of claim 1 for use in the treatment of a disease or disorder by inhibiting TYK2 mediated signal transduction in a subject suffering therefrom. Claim 18 is considered indefinite as it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q).
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 18 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.
According to MPEP §2111.02(II):
“If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
Furthermore, claim 17 recites a method for treating a disease or disorder by inhibiting TYK2 mediated signal transduction in a subject suffering therefrom, comprising administering the subject a therapeutically effective amount of the compound of claim 1. Claim 17 does not restrict the compound to any particular subset of compounds within claim 1. Instead, it encompasses all compounds of claim 1 for use in treating the diseases or disorders recited in claim 17.
Accordingly, claim 18 merely recites the compound of claim 1 for an intended use that is already encompassed by claim 17. The recitation “for use in the treatment of a disease or disorder by inhibiting TYK2 mediated signal transduction in a subject suffering therefrom” does not further limit the compound of claim 1 structurally. Therefore, claim 18 does not further limit claim 1 and is, in fact, a substantial duplicate of claim 1.
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 18 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See or example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
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 1-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-6 and 9-20 of U.S. Patent Application No. 18881281 (‘281)
claims 1-13 of U.S. Patent Application No. 18579862 (‘862)
Although the claims are not identical, they are not patentably distinct from each other because the compounds claimed in the co-pending application are obvious homologs of the compounds claimed in the present application.
The claim set of ‘281 discloses a compound of the following formula (herein, referred to as Formula-I-281):
PNG
media_image15.png
325
253
media_image15.png
Greyscale
.
Formula-I-281 (with the exception of the region indicated by the dashed circle) encompasses the corresponding structural regions of instant Formula (I). The main structural distinction between Formula-I-281 and instant Formula (I) resides in the circled region. Specifically, Formula-I-281 requires the substituent in that position to be -NH2, whereas instant Formula (I) recites that if the substituent in that position is an amino group, it can only be -NH(C1-6 alkyl) or a -NH(deuterated C1-6 alkyl) group.
According to MPEP 2144.09:
I. REJECTION BASED ON CLOSE STRUCTURAL SIMILARITY IS FOUNDED ON THE EXPECTATION THAT COMPOUNDS SIMILAR IN STRUCTURE WILL HAVE SIMILAR PROPERTIES
A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c).
II. HOMOLOGY AND ISOMERISM ARE FACTS WHICH MUST BE CONSIDERED WITH ALL OTHER RELEVANT FACTS IN DETERMINING OBVIOUSNESS
Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).
In other words, hydrogen and methyl are considered to be homologs, and substitution between homologous groups is a routine modification that is presumed to yield compounds with similar properties.
Thus, the claimed compounds are not patentably distinct from those of the co-pending application.
Regarding ‘862:
Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap between the instant claims and the co-pending application.
Further, claim 13 of ‘862 recites the following compound:
PNG
media_image16.png
267
220
media_image16.png
Greyscale
(see claim 13 of ‘862 claim set on pg. 6, 2nd row, 2nd compound). One of ordinary skill in the art would have found it obvious to make the non-deuterated form of the compound from claim 13 of ‘862 to form instant compound B40 (see instant claim 14):
PNG
media_image17.png
234
176
media_image17.png
Greyscale
.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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, JEFFREY H. MURRAY can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624