DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status
The present office action is in responsive to December 1, 2023 Amendment and Response to Pre-Formalities Notice and corresponding miscellaneous documents.
Claims 1-15, 17 and 20-21 are pending, claims 3-14, 17 and 20 are amended and claims 16 and 18-19 are cancelled in the above-identified application.
Priority
U.S. Pat. Appln. Ser. No.: 18/302,313, Filed: April 18/2023 is a U.S. Continuation of 17/075,004 , Filed: October 20, 2020, now U.S. Pat. No.: 11,661,423, which is a U.S. Continuation of 16/093,858, Filed: October 15, 2018, now U.S. Pat. No.: 10,844,067, which is a 371 Nat.’l Stage Entry of WO 2017/178845 A1 (i.e., PCT/GB2017/051077, Intern.’l Filing Date: April 18, 2017), which claims foreign priority to GB1606635.9, Filed: April 15, 2016.
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on April 18, 2023 is in compliance with the provisions of 37 CFR 1.97.
Accordingly, Information Disclosure Statements have been considered by the Examiner.
Examiner Comments: Unconventional Chemical Functional Group Definitions
It is generally accepted under US patent law that Applicants are allowed to be their own lexicographers, esp. in light of 35 USC 112(b). The instant application incorporates use of claim language not generally used in the chemical arts to define functional groups (i.e., with apparent definitional support in the specification). An example of this is found in the instant specification for allyl groups as follows:
PNG
media_image1.png
76
924
media_image1.png
Greyscale
However, while the unconventional notation is acceptable if defined, using standard nomenclature ((C1-C6)alkyl) is often preferred to reduce the risk of future claim construction disputes.
Claim Objections
[1] Claims 1 and 2, respectively, are objected to for claim format as being in improper format. For example, claim 1 recites:
"A compound, or a pharmaceutically acceptable salt or solvate thereof, having the structural formula (Id)" is stylistically awkward and potentially confusing as to whether the structural formula (Id) applies only to the "compound" or also to the "salt or solvate." (i.e., also rejection under 35 USC 112(a) below).
For improved clarity and to follow standard practice in the art, it is recommended that the claim be amended to recite:
“A compound of Formula (Id), or a pharmaceutically acceptable salt thereof.”
This amendment would more clearly associate the structural formula with the parent compound while explicitly including its salts”.
Likewise, a similar amendment should be made for claim 2 directed toa compound of Formula (If).
[2] Claims 1 and 4, respectively, are objected to for minor informalities, typographical errors and/or punctuation and not referring to definitions in the alternative. In particular, the variable HET is:
defined by a series of chemical structures that do not have commas separating each structure; and
is missing the alternative article in between the last two HET chemical structures substituents.
[3] Claims 1, 6-9 and 12 are objected to for the presence of the following types of limitations within parentheses: S(O)pRc (where p is 0, 1 or 2); (CH2)qNRcRd (where q is 1, 2 or 3); S(O)rRh (where r is 0, 1 or 2); S(O)r1Rk (where r1 is 0, 1, or 2); S(O)r2Rh (where r2 is 0, 1, or 2); (where s is 1, 2, or 3); (CH2)vNRjRk (where v is 1, 2, or 3); (CH2)v1NRj1Rk1 (where v1 is 1, 2, or 3); (CH2)yNRlRm (where y is 0, 1, or 2); and the like.
Applicants are requested to review and amend all claims to remove parentheses, either by adding appropriate punctuation before or after each integer definition or by setting apart all such integer definitions at the end of the claims.
Claim Rejections - 35 USC § 112
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, 12 and 13, respectively, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd para., 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.
In general, the claims of the present invention fail to define the metes and bounds of the claimed invention due to use of indefinite, vague, ambiguous or unclear or poorly defined functional terms and/or language (i.e., such that exact scope of the claimed invention cannot be ascertained) without support from the specification within the claim itself. Claims must particularly point out and distinctly the claimed invention. Moreover, claims identified above also lack clarity, due to unnecessary use of repetitive and/or redundant terms.
[1] Claim 1 lacks clarity, is indefinite vague, ambiguous and indeterminate, because it is unclear what the metes and bounds of the claimed invention are given that:
while claim 1 does not define “R3 = hydrogen”, but claims 12 and 13 dependent from claim 1 includes the definition “R3 = hydrogen”
PNG
media_image2.png
450
713
media_image2.png
Greyscale
[2] Dependent claims 12 and 13 are rejected for recitation of the variable R3 = “hydrogen”, which lacks antecedent basis from independent claim 1 from which it depends; i.e., claim 1 does not recite R3 is hydrogen.
Regarding [1] and [2] above, This inconsistency or internal contradiction within the scope of the claimed subject matter creates a lack of clarity as to whether the actual scope of R3 can or cannot include hydrogen in claim 1 and consequently in claims 12 and 13 renders claims indefinite such that the metes and bound of the claimed invention indeterminate.
To overcome these rejections, Applicants must amend the claims to provide clarity and specificity accordingly.
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.
Claims 12 and 13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim 1 upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 12 and 13 include or introduce subject matter (R3 = hydrogen) that is inconsistent with the apparent definition of R3 in 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 § 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 1-15, 17 and 20-21 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.
Claims 1-15, 17 and 20-21 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for:
[a] Pyrazolopyrimidines compounds of Formula D and Formula E as shown below:
PNG
media_image3.png
374
583
media_image3.png
Greyscale
; or
a pharmaceutically acceptable salt thereof” (i.e., as in claims 1-15);
[b] corresponding to compounds 1-88, intermediate compounds 1-28 and synthetic methods of making intermediates or final compounds, pharmaceutical compositions which comprises a compound of Formula (D) or (E) or a pharmaceutically acceptable salt thereof;
[c] methods of treating non-small lung and medullary thyroid cancers
DOES NOT reasonably provide enablement or sufficient guidance for:
Broad scope of ANY or ALL:
compounds of Formula (Id) or (If) or pharmaceutically acceptable salt, hydrates or solvates thereof;
corresponding pharmaceutical compositions thereof; and
uses of the above for treatment methods directed to cancers in general.
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 the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
Nature Of The Invention.
The nature of the invention relates to:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
2. Scope Of The Claims.
The scope of the claims relates to these classes exemplified by independent claim types:
PNG
media_image4.png
89
460
media_image4.png
Greyscale
PNG
media_image4.png
89
460
media_image4.png
Greyscale
Thus, the scope of claims is very broad.
3 & 4) State of the Art and Predictability In The Art.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally
considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (i.e., see MPEP 2164.03)
Amount Of Guidance Provided By Applicants and 6. Working Examples.
Applicants provide guidance in the detailed specification and working examples demonstrate the practicality of the claimed invention, which include detailed examples exemplified by:
Synthetic compound Final Examples 1-86 and corresponding intermediate Examples 1-28 and other intermediate examples at paras. [0748]-[0764], preparation methods and characterizing data thereof.
Other than specific compounds encompassed by the subgenus of Formulas (D) and/or (E), there is NO teaching in the specification directed to any other examples encompassing the:
Broad scope of claimed compounds encompassed by all generic formulas defined therein, and/or
solvates or hydrates of any of the compounds of any of the Formulas described therein.
Biological Data
PNG
media_image5.png
517
398
media_image5.png
Greyscale
PNG
media_image6.png
282
442
media_image6.png
Greyscale
PNG
media_image7.png
750
498
media_image7.png
Greyscale
While the claimed invention is directed to:
“A method for the treatment of cancer in a subject in need of such treatment, said method comprising administering a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt or hydrate thereof (i.e., as in claim 20)”
biological assay data set forth in the specification teaches specific engineered cell lines are often used to determine efficacy of selected compounds, such as those of the claimed invention to assist in identifying potential mechanisms of action; i.e., e.g., where:
PNG
media_image8.png
69
493
media_image8.png
Greyscale
PNG
media_image8.png
69
493
media_image8.png
Greyscale
The specification provides screening based on the above cell lines that are associated with the identified cancers (i.e., non-small lung cancer or medullary thyroid cancer), there is:
NO teaching directed to broad scope of all cancers, based on the insufficient examples in the specification (i.e., e.g., there is lack of target disease data, no identified specific disease indication,
NO basis for demonstrating any therapeutic effect or what compounds of the present invention adaptable for treatment of any or all cancers, if any.
Therefore, the instant application fails to satisfy the enablement requirement of 35 U.S.C. § 112(a) because the specification does not provide an adequate teaching for one of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation. The disclosure relies primarily on in vitro biochemical (e.g., RET and KDR IC50) and cell-based (e.g., BaF3, cancer cell lines) assay data. This data provides a mere starting point or "invitation to a research project" and does not establish a sufficient or reasonably predictable correlation to the claimed in vivo treatment of complex diseases such as medullary thyroid or non-small cell lung cancer in a patient. A person skilled in the art would have to engage in substantial and undue experimentation (such as conducting extensive animal studies or clinical trials not described) to bridge the significant unpredictable gap between the disclosed in vitro activity and the claimed therapeutic effect in the full scope of subjects.
Regarding noted above, these cannot be simply willed into existence. As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190 “The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However,...there is no evidence that such compounds exist...the examples of the '881 patent do not produce the postulated compounds...there is...no evidence that such compounds even exist.
The same circumstance appears to be true here. Hence, Applicants must show that the scope of claimed compounds and other requirements yields all the desired effects of scope claimed, other than those exemplified by the limited Experimental Example section of the present invention, where examples can be made/ used for the stated purpose in all situations across the board, not just in animals, but also in human subjects or limit the claims accordingly.
7. Level Of Skill In The Art (High)
An ordinary artisan in the area of drug development would have experience in screening chemical compounds for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
An ordinary artisan with expertise in the biological areas of molecular biology, immunology, biopharma, biotech, pharmacology, medicinal chemistry organic, biological, organic, and /or related drug development technologies would recognize the significance of biological mechanisms of action involving use of tubulin polymerization inhibitors for treatment of various types of cancer.
The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known.
Additionally, while high throughput screening assays can often be employed, developing a therapeutic method for a complex invention as claimed, is generally not well-known or routine, given the complexity of certain biological systems. Screening of new drug candidates, while complex, is routine in the art.
MPEP §2164.01 (a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here as Applicants are not enabled for making or using all these compounds (i.e., as described in general terms, inc., but not limited to starting materials, intermediates, etc.) or pharmaceutical compositions thereof (i.e., e.g., by using not specifically reagents and/or, reactions conditions, etc. ) or treating the diseases taught in the specification.
In summary, the instant application fails to satisfy the enablement requirement of 35 U.S.C. § 112(a) because the specification does not provide an adequate teaching for one of ordinary skill in the art to practice the full scope of the claimed invention, which includes the broad scope of compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions and treatment methods directed to all cancers without undue experimentation. The disclosure relies primarily on in vitro biochemical (e.g., RET and KDR IC50) and cell-based (e.g., BaF3, cancer cell lines) assay data. This data provides a mere starting point or "invitation to a research project" and does not establish a sufficient or reasonably predictable correlation to the claimed in vivo treatment of complex diseases such as medullary thyroid or non-small cell lung cancer in a patient. A person skilled in the art would have to engage in substantial and undue experimentation (such as conducting extensive animal studies or clinical trials not described) to bridge the significant unpredictable gap between the disclosed in vitro activity and the claimed therapeutic effect in the full scope of subjects. Thus, the specification does not set forth or indicate how a person of ordinary skill in the art could apply the instant invention in methods to activate any kinase, including AMPK or broad or specific disease types defined in the specification without resorting to undue experimentation; i.e., e.g.,:
the burden is on the applicant to show that the disclosure is enabling for the full scope of the claimed invention, but here, the disclosure of success based on multi oral dosing studies, without out indicating what diseases to treat is not commensurate with the breadth of the claim.
Accordingly, above-identified claims of the instant invention are non-enabled under 35 U.S.C. § 112(a).
Claim Rejections - 35 USC § 102
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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
THE CLAIMED INVENTION AS IT RELATES TO PRIOR REJECTIONS
While pending claim 1 does not appear to include “hydrogen: in the definition of R3, claims 12 and 13 dependent from claim 1 actually define R3 = “hydrogen”, which supports the presumption that an inadvertent omission was made in not including R3 = “hydrogen” by Applicants in claim 1 (i.e., see this noted under the rejection under 35 USC 112(b)):
Pending claim 1 relates to a compound of Formula (Id):
PNG
media_image9.png
232
193
media_image9.png
Greyscale
; or
a pharmaceutically acceptable salt or solvate thereof;
i.e., e.g.:
R3 ≠ “H” and
Het selected from a list inc.:
PNG
media_image10.png
227
228
media_image10.png
Greyscale
.
PNG
media_image2.png
450
713
media_image2.png
Greyscale
This is further supported by the fact that compounds recited in claim 15 (and in Table C of the instant specification), R3 = “hydrogen” and “halogen”.
Independent claim 15 recites compound species from Table C, where R3 = H and Halogen
Table C compounds, where:
R3 = “hydrogen”
R3 = “halogen”
Compounds 1, 2, 5, 6, 9, 11, 13, 15, 17, 20, 21, 22, 27, 28, 31, 32, 36, 37, 39, 40, 41, 42, 43, 44, 47, 50, 54, 70, 73, 74, 75, 84, 88
R3 = Cl
Compounds 3 , 4 , 7, 8, 10 , 12, 14, 16, 18, 19 , 23, 24, 25, 26, 29, 30, 33, 35, 38, 45, 46, 48 , 51, 52, 53, 55, 56, 57, 58, 59, 60, , 61, 62, 63, 64, 65, 66, 67, 68, 69, 71, 72, 77, 78, 79, 80, 81, 82, 83, 85, 86, 87- Cl
R3 = Br
Compounds 34, 49
R3 = F
Compound 76
Under the broadest reasonable interpretation that claims 12 and 13 are correctly dependent from claim 1, which inadvertently omitted R3 = “hydrogen” in error, then the following prior art reads on the claimed invention. As per rejections of record under 35 USC 112 (b) and (d), Applicants are requested to amend claim 1 to resolve to include R3 = “hydrogen” or amend claims 12 and 13 to delete R3 = “hydrogen” to eliminate this inconsistency.
This rationale is considered with regard to the following prior art rejections
PRIOR ART REJECTIONS
[1] Claims 12 and 13 are rejected under 35 U.S.C. 102(a)(1) as anticipated by US 2011/0224223 A1 to Shokat et al. (Filing Date: July 8, 2009 ).
[OR:
Claims 1-15, 17 and 20-21 are rejected under 35 U.S.C. 102(a)(1) as anticipated by US 2011/0224223 A1 to Shokat et al. (Filing Date: July 8, 2009 ) (i.e., if claim 1 inadvertently did not include R3 = “hydrogen”]
Sholat discloses and teaches:
compounds useful for treatment of cancer, including compound 3-3 (p. 15 and p. 38)
PNG
media_image11.png
329
225
media_image11.png
Greyscale
, which is a compound of formula 1b, where R1 is -L-Y-Q, where L is absent or 1-5C(alkylene), Y is absent, Q is (1-6C)alkyl, X1 is CH, R2 is 3C(alkyl), b is 1, and a is 0, (i.e., which covers compound 13 identified in Table C of the instant invention and reads on the claims 1-15, 17 and 20-21
pharmaceutical compositions comprising the disclosed compounds (Abstract, [0091], [0098], [0223]).
methods of treatment of cancer comprising administration of the disclosed compounds, including compound 3-3 (see [0016], [0159], [0163], including cancers selected from the cancers recited in claims 20-21 (i.e., non small lung cancer (NSCLC) and medullary thyroid cancer see paras. [0163], [0167]).
Therefore, the Sholat reference anticipates the claimed invention.
[2] Claims 12 and 13 are rejected under 35 U.S.C. 102(a)(1) as anticipated by U.S. Pat. No. 9,174,994 B2 to Liu et al. (i.e., PCT Filing Date: November 21, 2012; 371 Date: May 22, 2014; Issue Date: November 3, 2015; “U.S. ‘994 Pat.”).;
[OR:
Claims 1-15, 17 and 20-21 are rejected under 35 U.S.C. 102(a)(1) as anticipated by U.S. Pat. No. 9,174,994 B2 to Liu et al. (i.e., PCT Filing Date: November 21, 2012; 371 Date: May 22, 2014; Issue Date: November 3, 2015; “U.S. ‘994 Pat.”). (i.e., if claim 1 inadvertently did not include R3 = “hydrogen”)]
U.S. ‘994 Pat. discloses and teaches:
compounds useful for treatment of cancer, which include:
compound 48 (col. 231):
PNG
media_image12.png
229
136
media_image12.png
Greyscale
, which is a compound of formula 1b, where R1 is -L-Y-Q, where L is absent, Y is absent, Q is 6-membered heterocyclyl containing 1 N, X1 is CH, R2 is Cl, b is 1, and a is 0.
compound 23 (col. 217):
PNG
media_image13.png
239
137
media_image13.png
Greyscale
, which is a compound of formula 1b, where R1 is -L-Y-Q, where L is absent or 1-5C(alkylene), Y is absent, Q is (1-6C)alkyl, X1 is CH, R2 is NRj1Rk1, Rj1 is H, Rk1 is H, b is 1, and a is 0;
which read on claims 1-15, 17 and 20-21
pharmaceutical compositions comprising the disclosed compounds (Abstract, col. 13 lines 16-25, col. 253 lines 30-37, col. 257 line 48-col. 269 line 10).
methods of treatment of cancer comprising administration of the disclosed compounds, including compounds 23 and 48 (col. 5 lines 51-54, col. 248 lines 45-51, claims 1-21) including cancers recited in claims 20-21 (i.e., non small lung cancer (NSCLC) and medullary thyroid cancer see paras. (see col. 249-252).
Therefore, the U.S. ‘994 Pat. anticipates the claimed invention.
[3] Claims 22-23, 26, 30 and 35 are rejected under 35 U.S.C. 102(a)(2) as anticipated by the compound represented by CAS Registry No. 950187-48-1 (Database Registry Chemical Abstracts Service, Columbus, OH) entered 11 Oct 2007.
The reference compound has the following structural formula:
PNG
media_image14.png
436
301
media_image14.png
Greyscale
, which is a compound of formula 1b, where R1 is -L-Y-Q, L is absent, Y is absent, Q is C4alkyl, X1 is -CH, b is 0 and a is 0.
An electronic publication, including an on-line database or Internet publication, is considered to be a “printed publication” within the meaning of 35 U.S.C. 102(a) and (b) provided the publication was accessible to persons concerned with the art to which the document relates. See In re Wyer, 655 F.2d 221, 227, 210 USPQ 790, 795 (CCPA 1981). Since this date represents the date that each compound entered the Registry database on STN, this represents the date that each compound was made accessible to the public. See MPEP 2128: ELECTRONIC PUBLICATIONS AS PRIOR ART Status as a "Printed Publication".
The aforementioned compound anticipates the instantly-claimed compound genus. It is further noted that for the purposes of determining if a reference is a “printed publication” for the purposes of 102(b), MPEP 2128 states the following:
PNG
media_image15.png
124
600
media_image15.png
Greyscale
where “prior art disclosures…on an on-line database are considered to be publicly available as of the date the item was publicly posted.” Since each the database entry above lists the date that the compound was entered into the on-line database, the compound was made publicly.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
[1] Claims 1-15, 17 and 20-21 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,661,423 B2
(Filing Date: October 20, 2020; Issued: May 30, 2023).
[2] Claims 1-15, 17 and 20-21 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-14 22-23 and 26-27 of
U.S. Patent No. 11,548,896 B2 (Filed Date: February 2, 2021; Issued: January 10, 2023).
[3] Claims 1-15, 17 and 20-21 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-3, 5-7, 10-14, 16 and 20-22 of U.S. Pat. No. 10,844,067 B2 (i.e., PCT Filed: April 18, 2017; 371 Filing Date: October 15, 2018, Filing Date: May15, 2023; Issued: November 24, 2020).
[4] Claims 1-15, 17 and 20-21 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 10,954,241 B2 (i.e., PCT Filed: April 18, 2017; 371 Filing Date: October 15, 2018; Issued: March 23, 2021).
[5] Claims 1-15, 17 and 20-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 11-15, 21 and 24-25 of co-pending U.S. Appln. Ser. No. 18/967,321 (i.e., Filing Date: December 3, 2024)
With regard to each of the above non statutory and/or provisional non-statutory double patenting rejections:
although the conflicting claims are not identical, they are not patentably distinct from each other because the compounds encompassed by the genus of Formula (I) or pharmaceutically acceptable salts thereof (i.e., including other encompassed formulas defining other subgenus etc.), corresponding pharmaceutical compositions and/or treatment methods for cancer of the instant invention, because:
in general, the claimed invention overlaps in scope with the claimed matter of each of the patents and/or patent applications identified in the chart below, which encompass and read on each and every element of the claimed invention (i.e., including compounds, compositions/formulations, treatment methods for specific disease and the like); and
in particular, see chart below which generally indicates that overlapping subject matter is associated with the following variables in claim 1 and other dependent claims that correspond to:
R1, R2, [R2]b,X1 to X4 (i.e., inc. CR2, -L-Y-Q) groups and underlying functional groups; i.e., e.g., which primarily occurs at R1, R2, R3 positions in Formula (I) of the claimed invention and cited patent references.
Applicants are requested to carefully review and amend the claims to remove overlapping subject matter from the claims accordingly.
NON-STATUTORY OBVIOUSNESS-TYPE DOUBLE PATENTING REJECTION: PATENTED
CLAIMED INVENTION
REJECTED AS BEING UNPATENTABLE OVER CLAIMS
[1]
PNG
media_image16.png
1
28
media_image16.png
Greyscale
PNG
media_image16.png
1
28
media_image16.png
Greyscale
PNG
media_image17.png
29
392
media_image17.png
Greyscale
PNG
media_image16.png
1
28
media_image16.png
Greyscale
PNG
media_image16.png
1
28
media_image16.png
Greyscale
U.S. Pat. No. 11,661,423 B2
Issue Date May 30, 2023
Compound Claims 1-15, 17
Pharma composition 16
Methods for trmt of cancer 18-24
PNG
media_image18.png
73
142
media_image18.png
Greyscale
PNG
media_image18.png
73
142
media_image18.png
Greyscale
PNG
media_image19.png
365
426
media_image19.png
Greyscale
[2]
U.S. Pat. No. 11,548,896 B2
Issue Date January 10, 2023
Compound Claims 1-15, 17
Pharma composition 16
Methods for trmt of cancer 18-24
PNG
media_image20.png
520
462
media_image20.png
Greyscale
PNG
media_image21.png
276
296
media_image21.png
Greyscale
[3]
U.S. Pat. No. 10,954,241 B2
Issue Date March 23, 2021
Compound Claims 1-3, 5-7, 9-14 and 16
Pharma composition 20
Methods for trmt of cancer 21-22
PNG
media_image22.png
386
382
media_image22.png
Greyscale
PNG
media_image23.png
207
145
media_image23.png
Greyscale
[4]
U.S. Pat. No. 10,844,067 B2
Issue Date Nov 24, 2020
Compound Claims 1-15, 25-27
Pharma composition 16
Methods for trmt of cancer 17-24
PNG
media_image24.png
359
327
media_image24.png
Greyscale
PNG
media_image25.png
203
167
media_image25.png
Greyscale
PNG
media_image26.png
262
169
media_image26.png
Greyscale
Provisional Non-Statutory Double Patenting Rejection:
Claimed Invention
US Patent Over Claims
Claimed Invention are rejected as being unpatentable over claims
[5]
PNG
media_image16.png
1
28
media_image16.png
Greyscale
PNG
media_image16.png
1
28
media_image16.png
Greyscale
PNG
media_image17.png
29
392
media_image17.png
Greyscale
PNG
media_image16.png
1
28
media_image16.png
Greyscale
U.S. Pat. Appln. No. 18/967,321
Filing Date Dec. 3, 2024
Compound Claims 1-3, 5-7, 11-15
Pharma composition Claim 21
Trmt Methods for cancer claims 24-25
(inc. medullary thyroid & non-small cell lung cancer)
PNG
media_image27.png
429
709
media_image27.png
Greyscale
PNG
media_image28.png
151
163
media_image28.png
Greyscale
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 non-statutory double patenting context. See also Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008);Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
The ordinary artisan would recognize as obvious that determination of whether “said compounds were present in the prior art,” is implicit in the patented claim in view of Sun Pharmaceutical Industries, LTD. v. Eli Lilly and Company which states the following: “Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see U.S. Patent No. SUN PHARMACEUTICAL v. ELI LILLY 85,563,165 (“’165 patent”), at [57], col.1 11.11-14, col.3 11.3-27. The later patent then claimed a method of using these compounds for treating inflammation, inflammation-associated disorders, and specific inflammation-associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent No. 5,760,068 (“’068 patent”) col.97 1.49- col. 108 1.29. After rejecting the patentee’s objection to our consideration of the specification of the earlier patent, we determined that the later patent “merely claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier] patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent was invalid for obviousness-type double patenting. Id. at 1368.
However, one skilled in the art would recognize that the issued patent specifically contains the compounds of Formula (I) seen in claim 1 in the instant application.
A non-statutory obviousness-type 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); and In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985).
Obviousness-type double patenting requires rejection of an application claim when the claimed subject matter is not patentably distinct from the subject matter claimed in a commonly owned patent, or a non-commonly owned patent but subject to a joint research agreement as set forth in 35 U.S.C. 103 (c)(2) and (3), when the issuance of a second patent would provide unjustified extension of the term of the right to exclude granted by a patent. See Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 58 USPQ2d 1869 (Fed. Cir. 2001); Ex parte Davis, 56 USPQ2d 1434, 1435-36 (Bd. Pat. App. & Inter. 2000).
One having ordinary skill in the art at the time of the invention would have noted that subject matter exists in both the instant invention and the co-pending applications that is not patentably distinct from each other. It has also been held that a prior art disclosed genus of useful compounds is sufficient to render prima facie obvious a species falling within a genus. In re Susi, 440 F.2d 442, 169 USPQ 423, 425 (CCPA 1971), followed by the Federal Circuit in Merck & Co. v. Biocraft Laboratories, 847 F.2d 804, 10 USPQ 2d 1843, 1846 (Fed. Cir. 1989).
Appropriate action is required accordingly.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689.
The Examiner can normally be reached Monday-Friday 7:30 am - 6 pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicants 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 on 571-272-9023.
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.
/G.C.H./
Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624