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 .
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.
Election/Restrictions
Applicant’s election in the reply filed on 6 July 2026, is acknowledged. 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)).
Applicants provided a compliant species election of compound:
PNG
media_image1.png
98
222
media_image1.png
Greyscale
, which is a species of genus formula I of instant claims 1, 28, and 39, wherein:
PNG
media_image2.png
62
642
media_image2.png
Greyscale
.
Examiner did not find prior art on the elected species.
Therefore, the Examiner extended the Markush search to:
PNG
media_image3.png
206
202
media_image3.png
Greyscale
which has prior art, and which is a species of genus formula I of instant claims 1 and 39, wherein: X is CR2d,
Y is CR2b,
Z is CR2e,
R1 is H,
R2a is H,
R2b is H,
R2c is H,
R2d is H,
R2e is F,
R3 is a piperidine (“two R3’s, with the carbon to which they are both attached, form an optionally substituted heterocyclyl”),
L is C(R4)2,
R4 is H,
n is 2,
p is 3.
Therefore, per Markush search practice, the Examiner will not extend the Markush search unnecessarily for additional species in this Office Action.
The Markush search reads on claims: 1, 15-16, 19, 29-31, 35-36, 38-39, 42-43, and 45.
Claims 3, 14, 17, 23, and 25-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6 July 2026.
Current Status of 18/699,841
This Office Action is responsive to the amended claims of 6 July 2026.
Claims 1, 15-16, 19, 29-31, 35-36, 38-39, 42-43, and 45 have been examined on the merits. Claims 1 and 39 are original. Claims 15-16, 19, 29-31, 35-36, 38, 42-43 and 45 are previously presented.
Priority
The effective filing date of the instant application is: 11 October 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6 July 2026; and 6 November 2024, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 15-16, 19, 29-31, 35-36, 38-39, 42-43, and 45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Factors to be considered in making the determination as to whether one skilled in the art would recognize that the applicant was in possession of the claimed invention as a whole at the time of filing include: (a) Actual reduction to practice; (b) Disclosure of drawings or structural chemical formulas; (c) Sufficient relevant identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and knowledge in the art and (f) Predictability in the art. While all of these factors are considered, a sufficient number for a prima facie case are discussed below.
Applicants’ claims are drawn to the embodiment “prodrug”. Here, Applicant provides no guidance as to ‘prodrugs'. The artisan understands that prodrug forms are generally determined a posteriori, and it is only through trial and error that prodrugs are identified. The artisan understands the concept of prodrugs, however the artisan does not per se understand what specifically describes a specific prodrug form. The reference HAN (Han, H. “Targeted Prodrug Design to Optimize Drug Delivery.” AAPS Pharmsci. (2000), Vol. 2 (1) article 6, pp. 1-11), acknowledges there is no specific definition for prodrug (e.g. page 1), but that in general, the 'prodrug' is an inactivated form of the drug that activates in vivo to the active form. While some prodrugs are simply esters or salts, other prodrug forms are not chemically or structurally related to their active form, one example being glucose as the prodrug form of hydrogen peroxide (Table 1, page 5), as is hypoxanthine, thus posing a problem as to understanding what is the exact prodrug form of a compound, as hydrogen peroxide has two prodrug forms in the limited set of compounds exemplified in Han.
According to the reference ETTMAYER (Ettmayer, P., et al. “Lessons Learned from Marketed and Investigational Prodrugs.” J. Med. Chem. (2004) 47(10), pages 2393-2404), prodrugs are often accidental discoveries. Furthermore, the reference TESTA (Testa, B. “Prodrug research: futile or fertile?” Biochem. Pharm. (2004) 68, pages 2097-2106), teaches that, “A number of challenges await medicinal chemists and biochemists carrying out prodrug research, such as the additional work involved in synthesis, physicochemical profiling, pharmacokinetic profiling and toxicological assessment. Two of these challenges are introduced here, namely biological variability and toxicity potential. The challenge of biological variety results principally but not only from the huge number and evolutionary diversity of enzymes involved in xenobiotic metabolism. Inter- and intra-species differences in the nature of these enzymes, as well as many other differences such as the nature and level of transporters, may render prodrug optimization difficult to predict and achieve.” (Testa, page 2098).
Methods of making compounds, in general, are known to the artisan, however the methods of making any specific prodrug are complex and poorly understood, requiring an undue amount of experimentation to determine if a compound is actually a prodrug, and the instant specification fails to provide guidance to overcome the complexity and difficulties known to the artisan, as discussed above.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Thus, claims 1, 15-16, 19, 29-31, 35-36, 38-39, 42-43, and 45 are rejected under 35 USC 112(a) as lacking written description.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 15-16, 19, 29-31, 35-36, 38-39, 42-43, and 45 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
STOCKWELL (WO 2019/169306 A1, referenced in IDS of 6 Nov 2024).
The prior art reference STOCKWELL teaches a compound 12g:
PNG
media_image3.png
206
202
media_image3.png
Greyscale
(page 170, compound 12g), which is a species of genus formula I of instant claim 1, or a pharmaceutically acceptable salt (page 323, claim 38), stereoisomer (page 102, para [0312]):
wherein:
X is CR2d,
Y is CR2b,
Z is CR2e,
R1 is H,
R2a is H,
R2b is H,
R2c is H,
R2d is H,
R2e is F,
R3 is a piperidine (“two R3’s, with the carbon to which they are both attached, form an optionally substituted heterocyclyl”),
L is C(R4)2,
R4 is H,
n is 2,
p is 3,
This anticipates instant claims 1, 15-16, and 19.
The Examiner interprets the limitation "inhibitor of TYRO3" to be an inherent property or function of STOCKWELL per MPEP 2112.01(I) and (II). Therefore, this anticipates instant claim 29.
STOCKWELL further teaches a pharmaceutical composition (claim 11, page 300-305), pharmaceutically acceptable salt (claim 11, page 300-305), stereoisomer (para [0312], page 102), pharmaceutically acceptable carrier (claim 9, page 298), diluent (claim 11, page 300-305), and excipient (para [0254], page 86). This anticipates claim 30.
In connection to compound 12g as mapped above, STOCKWELL teaches a method for treating or ameliorating the effects of a disorder, wherein the disorder is a disease characterized by aberrant kinase levels in the subject (claim 28, page 318). Although STOCKWELL does not specifically identify “tyro3-mediated disease or disorder”, claims 35, 36, and 38 provide various diseases that supplement the definition to said “tyro3-mediated disease or disorder” as in claim 31. Therefore, due to the claim construction provided by the applicant, claim 31 is anticipated by STOCKWELL.
Claim 35, denoting a method for treating various diseases including leukemia, is anticipated by STOCKWELL, which teaches a method for treating leukemia using compound 12g (claim 33, page 318).
Claim 36, denoting a method for treating various disease including melanoma, is anticipated by STOCKWELL, which teaches a method for treating melanoma using compound 12g (claim 33, page 318).
Claim 38, denoting a method for treating various disease including astrocytoma, is anticipated by STOCKWELL, which teaches a method for treating astrocytoma using compound 12g (claim 33, page 321).
Claim 39 denotes a method for inhibiting a TYRO3-mediated disease or disorder by administering a compound of Structure (II), which is equivalent to Structure (I) presented in claim 1. In connection to compound 12g as mapped above, STOCKWELL teaches a method for treating or ameliorating the effects of a disorder, wherein the disorder is a disease characterized by aberrant kinase levels in the subject (claim 28, page 318). Although STOCKWELL does not specifically identify “tyro3-mediated disease or disorder”, claims 42, 43, and 45 provide various diseases that supplement the definition to said “tyro3-mediated disease or disorder” as in claim 39. Therefore, due to the claim construction provided by the applicant, claim 39 is anticipated by STOCKWELL.
Claim 42, denoting a method for treating various diseases including leukemia, is anticipated by STOCKWELL, which teaches a method for treating leukemia using compound 12g (claim 33, page 318).
Claim 43, denoting a method for treating various disease including melanoma, is anticipated by STOCKWELL, which teaches a method for treating melanoma using compound 12g (claim 33, page 318).
Claim 45, denoting a method for treating various disease including astrocytoma, is anticipated by STOCKWELL, which teaches a method for treating astrocytoma using compound 12g (claim 33, page 321).
Conclusion
No claims are presently allowable as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p.
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, Andrew D Kosar can be reached at (571) 272-0913. 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.
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
Prosecution Insights