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 of Claims
Claims 1-4 and 6-24 are pending. Claims 4 and 6-23 are withdrawn.
Priority
Instant application 17/850,720, filed 06/27/2022 claims priority as follows:
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Information Disclosure Statement
All references from IDS(s) received 05/18/2023 have been considered unless marked with a strikethrough.
Response to Amendment/Arguments
The amendment filed 03/20/2026 has been entered. Applicant has amended claims 1 and 3. Claim 5 has been cancelled. Claim 24 is new.
Claims 1 and 3 were previously rejected under 35 U.S.C. 102(a)(1) as being anticipated by DIETERS. In view of the amendments to claim 1 and 3, applicant has overcome the rejection. Therefore, the previous rejection under section 102(a)(1) is withdrawn.
Claims 1-3 and 5 were previously rejected under 35 U.S.C. 112(b) as indefinite. In view of the amendment to claim 1, applicant has overcome the rejection. Therefore, the previous rejection under section 112(b) is withdrawn.
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, 3, and 24 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, at least claim 1 is drawn to a composition comprising a caged mTOR inhibitor prodrug, wherein the prodrug comprises an mTOR inhibitor and a photo-removable caging moiety, wherein the caging moiety is bound to the inhibitor, wherein the caging moiety prevents the activity of the inhibitor, wherein the caging moiety is removable by exposure to visible light irradiation in vivo.
The “caged mTOR inhibitor” compounds recited by instant claim 1 are defined with partial structure, but are otherwise defined structurally. The structure provided in amended claim 1 is that the mTOR inhibitor and the caging moiety are “bound”; and the caging moiety is selected from the options now recited in the claim (e.g. DEACM, a boron-dipyrromethane derivative, etc.). Otherwise, the claim does not specify any particular structure of the mTOR inhibitor, nor does the claim explain how the mTOR inhibitor (which can vary considerably in structure) should be attached to the caging moiety to “prevent the activity of the inhibitor”.
A known correlation between the claimed genus (“caged mTOR inhibitor prodrug”) and the claimed function (“prevents activity of the inhibitor”) has not been established by the prior art; nor has the correlation been sufficiently disclosed by applicant. The skilled artisan must rely upon applicant’s disclosure in order to predict which of the many possible “caged mTOR inhibitor prodrugs” embraced by claim 1 possess the claimed function. However, Applicant has not explored and disclosed a representative number of species to adequately establish such a correlation. Instead, only two embodiments (cOSI-027 of FIG. 1 and the compound of FIG. 9, which is also a caged OSI-027 compound) are disclosed by applicant and tested for the functions recited in the claims.
Both compounds comprise a photo-caging moiety attached to OSI-027 through an ester linkage. No other point of attachment to the OSI-027 molecule was assessed. No other caging moieties were assessed with OSI-027. No other mTOR inhibitors were assessed with the caging moieties DEACM and Formula VIII. No guidance is provided establishing how the mTOR inhibitor should be attached to the caging moiety in order to ensure that when the inhibitor is caged, it lacks activity; and when the inhibitor is uncaged, the activity is restored.
A review of the prior art fails to provide the structure-function correlation which is missing in Applicant’s disclosure in order to support the entire claimed genus. For example, Sadovski et al. (Bioorganic & Medicinal Chemistry, Chemical Neurobiology, vol. 18, no. 22, Nov. 2010, pp. 7746–52) discloses caged rapamycin (page 7747, “(7-demethoxy-7-dimethoxy-2-nitrobenzyloxy-rapamycin” and page 7751, “C7-DMNB-caged rapamycin”). Sadovski discloses that “[c]aging was observed to block rapamycin activity very effectively” (page 7751, left side, 2nd para). The cage was attached to rapamycin at position 7 of the molecule as a benzyl ether.
Sadovski additionally teaches that “[a]n NBDF caged rapamycin could be produced by an analogous synthetic route. The larger size of the NBDF group may lead to even greater differences between caged and uncaged derivatives. While coumarin derivatives such as diethylaminocoumarin are appealing for longer wavelength uncaging, they have been reported to be ineffective for caging alcohols directly. Instead a 7-hydroxy rapamycin derivative would have to be caged as a coumarin carbonate” (page 7751, left side, 3rd para).
Note that Sadovski discloses a structure-function correlation, but it is specific to one mTOR inhibitor (rapamycin) and a one photocaging moiety (DMNB). The disclosure of Sadovski is insufficient to support the entire compound genus claimed by Applicant.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriads of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when the compounds are merely described partially. As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what elements must be present to achieve the recited functions.
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, the specification fails to provide adequate written description for the genus of claims 1, 3 and 24 and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to Arguments
In the Remarks filed 03/20/2026, applicant traverses the rejection and argues that a structure-function correlation is disclosed (Remarks, page 15). Applicant states that “[t]he prodrug is synthesized by masking a functional group of the mTOR inhibitor, such as carboxyl group, with a photo-removable caging moiety…[t]his masking with photo-removable caging moiety recited in amended claim 1 ensures that the prodrug does not exhibit inhibitory effects until irradiated with visible light.”
Applicant additionally argues that the disclosure extends beyond the reduced-to-practice embodiments (Remarks, page 16). Applicant states “the specification also provides a detailed description of mTOR inhibitors…as well as exemplary prodrugs and methodologies for building the caged mTOR inhibitor prodrug”. In response to the examiner’s assertion that the specification fails to establish where and how the mTOR inhibitor and the caging moiety would be attached in order to achieve the claimed function, applicant states that “such details are not required to satisfy the written description requirement. A person of ordinary skill in the art would recognize that the specification describes a representative functional group (a carboxyl groups) suitable for conjugation and provides an exemplary methodology for coupling photoremovable caging moieties to mTOR inhibitors through routine covalent linkage strategies” (Remarks, page 19). Applicant states that these methodologies are routine to synthetic chemists and are widely used in prodrug design to attach coumarin-based photoremovable groups to bioactive small molecules.
Applicants’ arguments have been fully considered but are not found persuasive.
MPEP 2163 provides guidelines for the examination under 35 U.S.C. 112(a), and states:
“For example, in the biotech art, if a strong correlation has been established between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
For a genus claim defined by function, the specification must establish a correlation between structure and the claimed function across the breadth of the genus. Here, applicant’s argument implicitly assumes a structure-function correlation, particularly that every mTOR inhibitor has some functional group whose masking with a photocage will (1) prevent mTOR inhibitory activity, (2) be synthetically feasible, and (3) be photocleavable to restore the active drug. This assumption breaks down for at least the following reasons:
First, the cageable functional handle is structure-specific. For OSI-027, the handle is the carboxylic acid. Applicant argued that for Torin2, it would be the amine; and for PI-103, it would be the phenol. But for many other mTOR inhibitors, there is no single obvious handle to cage. See, for example, OLEKSAK (European Journal of Medicinal Chemistry, vol. 238, Aug. 2022, p. 114498).
Oleksak is a review of mTOR inhibitor scaffolds reported in patents from 2015 to 2021 (Oleksak, title; abstract). Oleksak discloses mTOR inhibitors such as vistusertib (Fig. 4d) or datolisib (Fig. 4c):
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Oleksak discloses other mTOR inhibitors such as PKI-179 (Fig. 5) or omipalisib (Fig. 5):
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There is no single obvious functional “handle” to conjugate a caging group to in the above molecules that would predictably (1) prevent mTOR inhibitory activity, (2) be synthetically feasible, and (3) be photocleavable to restore the active drug.
The above examples represent a small subset of the second-generation mTOR inhibitor compounds disclosed in Oleksak. More compounds are disclosed in Figs. 6 and 7, and include chemotypes such as triazine derivatives, benzopyrazine derivatives, pyridopyrimidine derivatives, imidazolopyrimidine derivatives, pyridopyridine derivatives, and triazoloimidazoquinoline derivatives, pyrazole derivatives, piperazine derivatives, dihydroimidazopyrazinone derivatives, and dihydropyrazinopyrazinone derivatives. A significant number of the compounds disclosed by Oleksak do not have an obvious functional “handle” for conjugation.
Second, the relationship between caging and activity loss is unpredictable across the genus. For OSI-027, the carboxylic acid is on a peripheral cyclohexane and caging it apparently disrupts binding. But for other mTOR inhibitors with completely different structures from OSI-027, it is unclear where caging should be performed in order to disrupt binding and prevent activity. While published after the filing date, the prior art reference BRETON-PATIENT (ChemBioChem, vol. 25, no. 8, Apr. 2024, p. e202300855) demonstrates the unpredictability of identifying an appropriate photocaging site to prevent activity of a small molecule inhibitor.
Breton-Patient discloses the development of a photocaged TAM kinase inhibitor (Breton-Patient, abstract). The authors synthesized multiple prodrugs, installing a DEACM photocage (the same photocage recited in claims 1 and 24 and used in cOSI-027) at different positions of the molecule (Fig. 1c):
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Compounds 1 and 2 were 16-fold and 90-fold less active than the original inhibitor, whereas only compound 3 displayed no inhibitory effect (Breton-Patient, page 4, right side). The differences between compounds 1-3 were not predictable and could only be discovered by synthesizing and testing each compound individually. Therefore, a PHOSITA would have understood that the relationship between caging and activity loss across the genus of the instant claims is unpredictable.
Third, the caging chemistry is different for each functional handle/drug chemotype. Ester linkage for carboxylic acids, carbamate linkage for amines, carbonate linkage for phenols, etc. Each class requires a different synthetic route, and the photocleavage kinetics and efficiency differ for each linkage type. The specification demonstrates only one linkage type on one mTOR inhibitor (ester-linked DEACM to OSI-027’s carboxyl or ester-linked BODIPY to OSI-027’s carboxyl).
Therefore, while the specification demonstrates that the recited function is achievable for one specific mTOR inhibitor (OSI-027), it provides no structural or mechanistic basis for extending this to the hundreds of structurally diverse mTOR inhibitors encompassed by the genus of claims 1, 3, and 24. Moreover, the prior art shows that this extension is unpredictable. Accordingly, the rejection is maintained for claims 1, 3, and 24.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Dieters et al. (WO 2012024558 A2) in view of Reesing et al. (Current Medicinal Chemistry, vol. 24, no. 42, Jan. 2018) and further in view of Mateo et al. (British Journal of Cancer, vol. 114, no. 8, Apr. 2016, pp. 889–96; cited in IDS).
The elected species is drawn to a pharmaceutical composition comprising the mTOR inhibitor OSI-027 caged by DEACM.
Dieters discloses photoactivatable rapamycin compounds (i.e., mTOR inhibitors) and the use of photoactivatable rapamycin compounds to regulate the dimerization and/or activity of polypeptides in a light dependent manner (abstract). In particular, Dieters discloses a photoactivatable rapamycin compound, comprising a caging group attached to rapamycin or an analog thereof (para. [0007]). Dieters contemplates irradiation of the photoactivatable compound by any known means in the art (para. [0109]), which includes visible light.
Dieters does not explicitly disclose the elected species compound comprising OSI-027 attached to DEACM.
However, Dieters teaches that specific rapamycin analogs include, inter alia, OSI-027 (para. [0059]). Further, Dieters teaches that specific caging groups include, inter alia, compounds having the formula (para. [0066]):
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Dieters teaches DMACM, which comprises a dimethylamino substituent, whereas the elected species requires DEACM comprising a diethylamino substituent.
However, the prior art recognized DEACM as a visible-light activated photo-caging group. For example, Reesing is drawn to approaches towards photoactivated chemotherapy and teaches caged organic chemotherapeutic agents (abstract; page 4925, section 3.2). Reesing articulates a general problem with photoswitchable drugs, namely that the need of UV light for their activation limits their application (abstract). Ressing later suggests that photoactivatable drugs which are activated by visible or near-infrared (NIR) light are preferable (abstract and page 4906, right side). Reesing teaches various prodrugs of paclitaxel comprising photocleavable coumaroyl moieties, including compound 68 which comprises DEACM (page 4934, Fig. 31A).
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (A) and/or (G), it would have been prima facie obvious to prepare a photoactivatable mTOR inhibitor comprising OSI-027 and DEACM as a photocaging moiety. Dieters teaches that the caging group can be linked to the rapamycin or analog thereof by any suitable linkage including, without limitation, carbonate, ether, ester, carbamate, or urea linkage (para. [0067]. OSI-027 has a carboxylic acid which the person having ordinary skill would have recognized as a suitable linkage point to form an ester with the DEACM photocage. Light-mediated activation enables special and temporal control of rapamycin (and rapamycin analog)-mediated protein dimerization and regulation of kinases (see Dieters, para. [0134]). Therefore, a skilled person would have been motivated to prepare a photocaged variant of OSI-027.
With respect to the intended “use” of the composition of claim 1 for the treatment of cancer, the prior art recognized OSI-027 for treating cancer. See, for example Mateo et al. which discloses that mTOR is a well-established target for cancer therapy and discloses a dose-finding study of OSI-027 in patients with advanced solid tumors (abstract). Mateo teaches that OSI-027 inhibits mTORC1/2 in patients with solid tumors in a dose-dependent manner but doses above the tolerable levels in S1 and S3 are required for a sustained biological effect in tumor biopsies (abstract, conclusions).
In the context of chemotherapy, Reesing teaches that as light can be delivered with very high spatiotemporal resolution, light-activated compounds are a promising strategy to selectively activate cytotoxic drugs at their site of action and thus to improve the tolerability and safety of chemotherapy (see Reesing, Abstract). Therefore, a skilled person would have been motivated to prepare a photocaged variant of OSI-027 for use in the treatment of cancer.
With respect to the limitation requiring that the composition comprises a dosage of between about 0.1 mg/kg body weight and about 1000 mg/kg body weight, Mateo teaches a potentially effective dose for OSI-027 of 120 mg QD 3 consecutive days per week.
However, differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. In the instant case, the dose of the photocaged OSI-027 compound is considered a result-effective variable that impacts, for example, the effectiveness of the treatment or the occurrence of non-tolerable side effects. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
Accordingly, claims 1-3 and 24 are rejected.
Response to Arguments
In the Remarks filed 03/20/2026, applicant traverses the rejection and argues that Dieters does not disclose or suggest cancer treatment or pharmaceutical compositions suitable for treating disease in a subject.
Applicant’s arguments have been fully considered but are not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The rejection is based on the combination of Dieters, Ressing, and Mateo. Dieters is drawn to photoactivation of caged rapamycin and rapamycin analogs for photo-control of rapamycin and rapamycin analog activity. Mateo teaches that mTOR inhibitors (i.e., rapamycin, rapamycin analogs, and the particular mTOR inhibitor OSI-027) are known in the art as having anti-cancer activity. Applicant’s own specification (“Background of the Invention”) extensively admits that OSI-027 therapy induces significant adverse effects, and that there is a need to improve the specificity of OSI-027 as a therapeutic drug, and to significantly reduce or avoid the adverse effects associated with mTOR inhibition as anti-cancer therapy. Reesing teaches that as light can be delivered with very high spatiotemporal resolution, light-activated compounds are a promising strategy to selectively activate cytotoxic drugs at their site of action and thus to improve the tolerability and safety of chemotherapy.
Applicant argues that the prodrugs in Dieters “focus on decaging under UV light”. Applicant points to para. [0109] in Dieters and states “Dieters teaches photo-removal of a caging group using UV light irradiation in the range of 10 nm to 400 nm” (Remarks, page 23). But the above statement from applicant is missing the full context of Dieters’ para. [0109]. The full para. [0109] passage in Dieters states:
The photoactivatable rapamycin compound can be irradiated at an appropriate wavelength or wavelength range and for a sufficient period of time to remove the caging group, e.g., a sufficient period of time to modulate the activity of the polypeptide comprising the RBD. If the rapamycin is a photoswitchable compound, the compound can be activated repeatedly by supplying and removing irradiation or by using two different wavelengths, one for activation and one for deactivation. The level of activation can be regulated by controlling the level and/or time of irradiation. In certain embodiments, irradiation can lead to deactivation of the first polypeptide (e.g. , using photoactivatable compounds comprising photoswitchable groups). For example, irradiation at one wavelength can lead to activation of the polypeptide while irradiation at a second wavelength leads to deactivation of the polypeptide. Irradiation can be provided by any means known in the art, e.g., by using a broad spectrum ultraviolet light (e.g., in the range of about 10 nm to about 400 nm) or a light providing a narrower wavelength range, such as UV-A light (about 315 nm to about 400 nm), or a single wavelength (e.g., about 365 nm), e.g., using a UVP UVGL-25 transilluminator.
It is clear from Dieters that means other than UV light are contemplated, and a PHOSITA would recognize visible light as an “appropriate means” or “appropriate wavelength” depending on the photocleavable group employed. Indeed, the specific wavelength used to activate a photocleavable group is considered a result-effective variable which the skilled artisan is equipped to arrive at through routine optimization.
Applicant argues that amended claim 1 recites DEACM and that “Reesing and Mateo do not disclose any of the caging groups recited in amended claim 1”.
Applicant’s argument has been fully considered but is not found persuasive. As noted in the rejection, Reesing teaches the photoremovable caging group DEACM in compound 68 (Reesing, page 4934). A person having ordinary skill, in search of a photocleavable group for OSI-027 and recognizing the carboxyl group as an obvious “functional handle” for photocaging, would have been motivated to selected an alcohol-containing photocage such as DEACM to prepare an ester. As admitted by Applicant in their remarks (page 20), “These reactions are routine methodologies of synthetic chemists and are widely used in prodrug design to attach coumarin-based photoremovable groups to bioactive small molecules”. The person having ordinary skill would have enjoyed a reasonable expectation that the resulting ester could have been cleaved under irradiation with light to release the active OSI-027 compound.
Accordingly, the rejection is maintained for claims 1-3 and new claim 24.
Conclusion
Claims 1-3 and 24 are rejected. Claims 4 and 6-23 are withdrawn.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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