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 .
Claims 1, 11, and 15 have undergone amendments. Claims 2, 17 and 18 have been cancelled. Thus, claims 1, 3-12, 14-16, and 19-21, submitted on 6 August 2025, represent all claims currently under consideration.
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.
Response to Amendment
The objection to Claim 11 is withdrawn. Applicant has amended the claim to recite “wherein”.
Applicant has amended claim 1 to recite a singular salt, rather “pharmaceutically acceptable salts”.
The 35 U.S.C. § 112(a) rejection of Claims 1 and 3-14 is withdrawn. Applicant has amended the claim to specify that the method is for the treatment of non-small cell lung cancer.
The 35 U.S.C. § 112(b) rejections of Claim 18 are withdrawn. Applicant has cancelled the claim, rendering the rejections moot.
The 35 U.S.C. § 102 rejections of Claims 1, 3-8, 11-12, 14-17, and 19-21 over Towner 1, 2, 3, and 4 are withdrawn. Applicant has amended the claims to specify that the cancer to be treated is non-small cell lung cancer, which is not disclosed by the references cited in the prior office action.
The 35 U.S.C. § 102(a)(1) rejection of Claims 12, 14, 15, 16, 19, and 21 over Dong (US 2012/0197059; Publication Date: 2 August 2012) is withdrawn. Applicant has amended the claims to specify that the cancer to be treated is non-small cell lung cancer, which Dong does not state is being treated, and further has amended the claims to require a coating layer which Dong does not describe.
Applicant’s amendment, see Page 8, filed 6 August 2025, with respect to the rejection(s) of claim(s) 15-17 and 19-21 under 35 U.S.C. § 102 (a)(1) over Kopke (WO 2019/213245) have been fully considered and are persuasive as applicant has amended Claim 15 to include the limitation of the coating layer. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made over Kopke (WO 2019/213245) in view of Maderuelo (European Journal of Pharmaceutical Sciences, 138, 2019).
Applicant’s amendment, see Page 9, filed 6 August 2025, with respect to the rejection(s) of claim(s) 15-17 and 19-21 under 35 U.S.C. § 102 (a)(1) over Carney (US Patent No. 5,780,510) have been fully considered and are persuasive as applicant has amended Claim 15 to include the limitation of the coating layer. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made over Carney (US Patent No. 5,780,510) in view of Maderuelo (European Journal of Pharmaceutical Sciences, 138, 2019).
The 35 U.S.C. § 102(a)(1) rejection of Claims 12, 14, 15, 16, 19, and 21 over Garland is withdrawn. Applicant has amended the claims to specify a dosage of a range of about 5 mg/kg bodyweight/day to about 1,000 mg/kg bodyweight/day, while Garland discloses data demonstrating a range from between 1 and 3 mg/kg, which is outside of the claimed range. Garland also fails to disclose a composition comprising a coating layer that encapsulates the 2,4-ds-PBN which solubilizes at a pH of greater than about 5.0.
Response to Arguments
Applicant's arguments filed 6 August 2025 with respect to the 35 U.S.C § 102(a)(1) rejection of Claims 15-18 and 21 over Gammans (US 2018/0200192; Publication Date: 19 July 2018) have been fully considered but they are not persuasive. Applicant claims that while Gammans discloses a range of 250 to 3000 mg and that this is a fixed dosage regardless of the body weight of the subject, whereas the composition is a weight-based dosage that scales relative to the body weight of the subject. The Examiner disagrees. This dosage range falls within the range of what is claimed in the examined application, and the claims are written with an intended use, and as the prior art is capable of performing this intended use, it anticipates the limitations of the claims. The composition of Gammans anticipates the claimed usage as the intended use of the claimed invention does not result in a structural difference between the claimed invention and what is described in the prior art (See MPEP § 2122.2 (II)). The composition of Gammans has doses or amounts of constituents. Establishing pH, doses, or amounts of constituents is not patentable. In re Aller, 105 USPQ 232, 232; 220F. 2d 454, 456 (CCPA, 1955). “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges”. In re Aller, 105 USPQ 232, 235 (CCPA, 1955), In re Russel, 169 USPQ 426, 439 F2d 1228 (CCPA, 1971).
Applicant's arguments filed 6 August 2025 with respect to the 35 U.S.C. § 103 rejection of Claims 1-12 and 14-21 have been fully considered but they are not persuasive. Applicant claims that Woo teaches away from the use of OKN-007 for the treatment of NSCLC, and that one of ordinary skill in the art would not expect tumor growth of NSCLC to be inhibited based off of the data of Woo. Applicant further states that the reliance on Lemjabbar-Alaoui is misplaced and that the reference does not teach that SULF2 is essential for tumor growth, citing a study referencing the methylation of SULF2 in NSCLC progression, stating that the patients which had methylated SULF2 did not have significantly greater median progression free survival compared to patients that did not have methylated SUFL2, stating that the artisan would know that methylation of SULF2 may result in inhibition of SULF2 activity, and that the data presented in Exhibit A indicates that inhibiting SULF2 activity does not necessarily improve the survival rates in a statistically significant manner. The Examiner disagrees. Woo was not intended to demonstrate that OKN-007 is toxic towards non-small cell lung cancer, as none of the cell lines which were tested are non-small cell lung cancer cell lines. Woo demonstrates a mechanism by which this compound functions, which is through inhibition of expression of SULF2, and demonstrates that the inhibition of SULF2 has utility in the treatment of certain types of cancer. Lemjabbar-Alaoui establishes that SULF2 is crucial to the growth of NSCLC, and that in human samples, there is increased expression of SULF2 and levels of Sulf-2 protein in two major classes of NSCLC. When this is knocked down, the NSCLC reversed their phenotypes in vitro and blunted xenograft tumor formation in nude mice. When non-malignant bronchial epithelial cells were forced to express Sulf-2, they transformed into a cancerous phenotype, supporting an essential role for Sulf2 in the pathogenesis of NSCLC. When NSCLC cells were transfected with Sulf-2 specific shRNAs, cell proliferation was significantly decreased, and tumors derived from cells that underwent this knockdown grew at markedly slower rates than the control. Taken together, these data indicate a crucial role for Sulf2 in the growth of NSCLC, and demonstrate that when this is knocked down and expression and activity are decreased, cancer cell viability and tumor growth is significantly reduced. Thus, this provides both a motivation and a reasonable expectation of success in applying the known cancer treatment of OKN-007 to treat NSCLC, as the mechanism by which it operates (inhibition of expression of SULF-2) has been shown to inhibit the growth of NSCLC.
Claim Rejections - 35 USC § 112(a)- NEW GROUNDS OF REJECTION
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 19 and 20 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 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 of structural chemical formulas; (c) Sufficient 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:
The claims are directed to a pharmaceutical composition comprising a therapeutically effective amount of 2,4-ds-PBN, wherein the composition comprises at least one coating layer, wherein the at least one coating layer encapsulates the 2,4-ds-PBN or pharmaceutically acceptable salt thereof and solubilizes at a pH of greater than about 5.0 in a physiological environment, with Claims 18 and 19 further claiming that this formulation is in the form of a solution or a liquid for intravenous injection or intra-arterial injection. The use of enteric coated formulations (formulations which remain insoluble in the acidic stomach environment but solubilize in the higher pH small and large intestines) are well known in the art, and are commonly employed for the formulation and delivery of oral pharmaceutical formulations. The specification does not provide any examples of a formulation of 2,4-ds-PBN which has at least one coating layer that encapsulates the compound and solubilizes it at a pH of greater than 5.0 and is formulated for IV or intraarterial delivery. The artisan would generally have the skills to develop oral formulations of this compound which have enteric coatings and are capable of solubilizing at pH values greater than 5.0, but would lack the skills and training to develop a formulation, which has an enteric coating, that is in a form of a solution or a liquid for IV or intra-arterial injection. There are no examples in the pharmaceutical arts of enteric coated formulations that are specifically in a form suitable for IV or intraarterial injection. Therefore, there is no support in the specification that would lead one of ordinary skill in the art to recognize that applicant was in possession of the claimed invention as a whole at the time of filing.
Claim Rejections - 35 USC § 102- REJECTIONS MAINTAINED
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 15, 16, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gammans (US 2018/0200192; Publication Date: 19 July 2018).
Gammans (See IDS, 24 August 2024) discloses compositions comprising N-acetylcysteine and a second compound that is a pharmaceutically acceptable compound capable of forming a radical adduct and a coating layer encapsulating at least the first compound (Abstract). In some embodiments, the second compound is 2,4-disuflophenyl-N-tert-butyl nitrone (Paragraph 0008). In some embodiments, the coating layer encapsulates the first and second compound. In some embodiments, the coating layer solubilizes at a pH greater than 7.0 in a physiological environment. In some embodiments, the composition is a pharmaceutical composition suitable for oral administration (Paragraph 0008). In some embodiments, the second compound is in the form of pellets, and the pellets comprise a core that contains the second compound and a coating encapsulating that core prevents the release of the second compound at a pH of less than 5.5. In some embodiments, the second compound is 2,4-disuflophenyl N-tert-butyl nitrone. In some embodiments, the modified release pharmaceutical composition is in the form of a capsule (Paragraph 0010). In some embodiments, the amount of pharmaceutically acceptable compound capable of forming a radical adduct is administered in an amount of from about 250 mg to about 3000 mg based on the weight of the pharmaceutically acceptable compound capable of forming a radical adduct moiety (Paragraph 0012). Claims 15 and 21 are written as “intended use” claims, and as such, this composition anticipates the claimed usage as the intended use of the claimed invention does not result in a structural difference between the claimed invention and the prior art (See MPEP § 2122.2 (II)). The range of dosages described by Gammans (250 to 3000 mg) falls within the claimed dosage range of 5 mg/kg body weight to 1,000 mg/kg body weight for 50 kg (5 mg/kg body weight to 60 mg/kg body weight) to over 100 kg body weight (0.25 mg/kg body weight to 30 mg/kg body weight). The composition of Gammans has doses or amounts of constituents. Establishing pH, doses, or amounts of constituents is not patentable. In re Aller, 105 USPQ 232, 232; 220F. 2d 454, 456 (CCPA, 1955). “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges”. In re Aller, 105 USPQ 232, 235 (CCPA, 1955), In re Russel, 169 USPQ 426, 439 F2d 1228 (CCPA, 1971).
Claim Rejections - 35 USC § 103- REJECTIONS MAINTAINED AND NEW GROUNDS OF REJECTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3-12, 14-16, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Woo (US 2020/0085802; Publication Date: 19 March 2020, Priority to KR2017-0034642, Date: 20 March 2017) in view of Lemjabbar-Alaoui (Oncogene, 2010, 29 (5):635-646), Towner (US 2017/0027891; Publication Date: 2 February 2017) and Maderuelo (European Journal of Pharmaceutical Sciences, 138, 2019).
Woo teaches a method to increase sensitivity to sorafenib treatment using inhibition of the SULF2 gene (Abstract). Woo demonstrates that treatment of HepG2, Huh7, and Hep3B cells with OKN-007 inhibits expression of SULF2, and increases susceptibility of these cells to apoptosis with sorafenib (Figure 9, Paragraph 0028). Woo demonstrates that OKN-007 (2,4-ds-PBN) inhibits expression of SULF2, and this has utility in the treatment of cancer.
Woo does not demonstrate that demonstrate that SULF2 inhibition is an effective treatment of non-small cell lung cancer.
Lemjabbar-Alaoui teaches the role of Sulf2 in the growth of NSCLC. Heparan sulfate proteoglycans (HSPGs) regulate the signaling of growth factors and morphogens. Sulf-1 and Sulf-2 are extracellular neutral pH sulfatases and are involved in the post-synthetic regulation of HSPG function, modulating several signaling pathways including Wnt signaling. They found increased expression of SULF2 and increased Sulf-2 protein in human lung adenocarcinoma and squamous cell carcinoma, two major classes of non-small cell lung cancer, and confirmed widespread Sulf-2 protein expression in human specimens. shRNA-mediated SULF-2 knockdown in 5 Sulf-2+ NSCLC cell lines reversed their transformed phenotype in vitro, eliminated autocrine Wnt signaling, and blunted xenograft tumor formation in nude mice. Forced Sulf-2 expression in non-malignant bronchial epithelial cells produced a transformed phenotype. The results support an essential role for Sulf-2 in lung cancer (Abstract). Transduction of cells with one of two Sulf-2 specific shRNAs inhibited cell proliferation by 44 to 50% in all tested cell lines. Knocked of Sulf2 increased apoptosis by 2-3 fold, indicating that Sulf2 promotes cell growth in lung cancer cell lines (Page 4). Tumors derived from cells that underwent Sulf2 knockdown grew at markedly slower rates than control (60-85% reduction) (Figure 5).
Towner (See IDS, 24 August 2024) teaches the use of 2,4-ds-PBN in the treatment of gliomas. The 2,4-ds-PBN may be used alone or combined with other traditional chemo- and radiotherapies and surgery, to treat gliomas occurrence, recurrence, spread, growth, metastasis, or vascularization (Abstract). The effective dose may be from about 5 to about 150 mg/kg body weight per day. Administering may be through oral administration in the form of a pill or in liquid form, or via intravenous injection (Paragraph 0015). In one embodiment, 2,4-ds-PBN may be used in conjunction with another glioma therapy, such as radiation, PCV, DFMO, CCNU, or BCNU (Paragraph 0065). The 2,4-ds-PBN therapy may precede or follow the other agent treatment by intervals ranging from minutes to weeks. In some situations, it may be desirable to extend the time period for treatment significantly, however, where several days or weeks lapse between administrations (Paragraph 0066). Figure 4 represents a series of MRI images taken over a period of 25 for an untreated group and representative data for 2,4-ds-PBN treated rats, showing that for PBN treating rats, the C6 glioma tumor volumes decreased by more than 15-fold compared to untreated (Paragraph 0121). Claim 33 claims the treatment method using 2,4-ds-PBN where it is administered enterally, intravenously, or intraarterially. Figure 6 illustrates that 2,4-dsPBN in rat C6 cells is found to be pro-apoptotic as concentration increases. The figure demonstrates that pro-caspase 3 and 9 increase in expression with increasing concentration of OKN-007 (Paragraph 0027). Pro-caspase 3 and 9 are markers of apoptosis within cells.
Maderuelo reviews the benefits of enteric coating. Enteric coating is commonly used in the development of oral pharmaceutical dosage forms, protecting the drug from the acidic pH and enzymatic degradation in the stomach (Abstract). This method guarantees the stability of the drug and ensures its release in the digestive tract (Page 1). There are several motivations for enteric coating, including altering the odor or taste of the drug, protecting against environmental conditions, protection of gastric mucosa against irritation, or allowing for site or time specific drug release (Page 2, Enteric Coating and its Function).
Woo, Lemjabbar-Alaoui, Towner, and Maderuelo are considered analogous to the claimed invention as all are involved in the development of pharmaceuticals. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use OKN-007 for the treatment of NSCLC, as Woo demonstrates that it is an inhibitor of SULF2, and Lemjabbar-Alaoui demonstrates that knockdown of SULF2 blunts NSCLC xenograft tumor formation and induces apoptosis of NSCLC cells in vitro, providing the artisan a reasonable expectation of success in applying the known SULF2 inhibitor OKN-007 for the treatment of NSCLC. Towner establishes dosing of OKN-007 for the treatment of cancers such as gliomas, describes both oral and intravenous formulations of this compound, and combinatorial treatment strategies of OKN-007 and other chemotherapeutics, radiation, or surgery. For oral dosage forms, Maderuelo describes the well-known technique of enteric coating, and as such, The use of enteric coating on the formulations is prima facie application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)), wherein the known technique is enteric coating of oral formulations, as described by Maderuelo, applied to the known oral formulations of OKN-007 Towner, predictably resulting in an oral formulation that will solubilize at a pre-determined range of pH values. Claims 15 and 21 are written as “intended use” claims, and as such, this composition anticipates the claimed usage as the intended use of the claimed invention does not result in a structural difference between the claimed invention and the prior art (See MPEP § 2122.2 (II)). The range of dosages described by Towner (5 to 150 mg/kg body weight per day) falls within the claimed dosage range of 5 mg/kg body weight to 1,000 mg/kg body weight.
Regarding Claims 9 and 10, Towner teaches that this compound induces apoptosis, and demonstrates an increase in apoptosis by measuring the levels of the caspases 3 and 9, which are well-known markers of apoptosis. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify this measurement of markers of apoptosis to counting apoptotic cancer cells and/or tumor cells. The artisan would recognize that caspases 3 and 9 are markers of apoptosis, and it flows from the data of Towner that this treatment induces apoptosis in tumor cells; the artisan would have a reasonable expectation that this increase in molecular markers of apoptosis would translate to an increase in apoptotic cancer or tumor cells when measured using other techniques, such as immunohistochemistry for markers such as caspase 3 or 9, or flow cytometry using markers for cellular death.
Claims 15, 16, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Carney (US Patent No. 5,780,510) in view of Maderuelo (European Journal of Pharmaceutical Sciences, 138, 2019).
Carney discloses 2,4-ds-PBN and its pharmaceutically acceptable salts (Abstract). The compound can be formulated into pharmaceutical compositions suitable for oral or parenteral, e.g., intravenous or intramuscular injection administration (Column 6, Lines 17-19). With oral dosing, one to three oral doses per day, each from about 0.02 to about 50 mg/kg are called for (Column 7, Lines 27-28). Intravenous dose levels for treating conditions range from 0.1 mg/kg/hour to at least 10 mg/kg/hour, all for from about 1 to about 120 hours and especially 24 to 86 hours. A preloading bolus of from about 10 to about 500 mg may be administered to achieve adequate steady state levels (Column 6, Lines 56-61).
Carney does not disclose the use of an enteric coating on the formulation of 2,4-ds-PBN.
Maderuelo, as described previously, teaches the use of enteric coating of oral pharmaceutical formulations, and describes the benefits of this technique.
Carney and Maderuelo are considered analogous to the claimed invention as all are involved in the development of oral formulations of pharmaceuticals. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply an enteric coating, as taught by Madeuelo, to the oral formulations of 2,4-ds-PBN of Carney. Enteric coating to protect oral formulations from degradation in the stomach is commonly used in the pharmaceutical arts, and as Maderuelo teaches, is used to guarantee the stability of the drug and protect the gastric mucosa against irritation. The use of enteric coating on the formulations of Carney is prima facie application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)), wherein the known technique is enteric coating of oral formulations, as described by Maderuelo, applied to the known oral formulations of Carney, predictably resulting in an oral formulation that will solubilize at a pre-determined range of pH values. Claims 15 and 21 are written as “intended use” claims, and as such, this composition anticipates the claimed usage as the intended use of the claimed invention does not result in a structural difference between the claimed invention and the prior art (See MPEP § 2122.2 (II)). The dosages described for both oral administration (0.02 to 50 mg/kg) and intravenous dosing (0.1 mg/kg/hour to 10 mg/kg/hour for 1 to about 120 hours) falls within the claimed dosage ranges of 5 mg/kg body weight/day to 1,000 mg/kg body weight per day. The composition of Carney has doses or amounts of constituents. Establishing pH, doses, or amounts of constituents is not patentable. In re Aller, 105 USPQ 232, 232; 220F. 2d 454, 456 (CCPA, 1955). “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges”. In re Aller, 105 USPQ 232, 235 (CCPA, 1955), In re Russel, 169 USPQ 426, 439 F2d 1228 (CCPA, 1971).
Claims 15, 16, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kopke (WO 2019/213245; Publication Date: 7 November 2019) in view of Maderuelo (European Journal of Pharmaceutical Sciences, 138, 2019).
Kopke discloses a method for reducing accumulated pathologic tau proteins in a subject in need thereof comprising administering 2,4-ds-PBN (Abstract). In some embodiments, the 2,4-ds-PBN is administered as a pharmaceutical composition which further comprises a pharmaceutically acceptable carrier (Paragraph 0004). In some embodiments, the 2,4-ds-PBN is administered to the subject orally, intravenously, subcutaneously, sublingually, sub-dermally, intrathecally, by inhalation, or within an ear (Paragraph 0005). The 2,4-ds-PBN can be administered at a dose of between 1 mg/kg to about 500 mg/kg body weight (Paragraph 0033).
Kopke does not disclose the use of an enteric coating on the formulation of 2,4-ds-PBN.
Maderuelo, as described previously, teaches the use of enteric coating of oral pharmaceutical formulations, and describes the benefits of this technique.
Kopke and Maderuelo are considered analogous to the claimed invention as all are involved in the development of oral formulations of pharmaceuticals. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply an enteric coating, as taught by Madeuelo, to the oral formulations of 2,4-ds-PBN of Kopke. Enteric coating to protect oral formulations from degradation in the stomach is commonly used in the pharmaceutical arts, and as Maderuelo teaches, is used to guarantee the stability of the drug and protect the gastric mucosa against irritation. The use of enteric coating on the formulations of Kopke is prima facie application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)), wherein the known technique is enteric coating of oral formulations, as described by Maderuelo, applied to the known oral formulations of Kopke, predictably resulting in an oral formulation that will solubilize at a pre-determined range of pH values. The composition of Kopke anticipates Claim 21 and Claim 15 as the claims have intended use language, and this composition is capable of performing this function, anticipating the limitation. The range of dosages described by Kopke (1 to 500 mg/kg body weight per day) falls within the claimed dosage range of 5 mg/kg body weight to 1,000 mg/kg body weight. The composition of Kopke has doses or amounts of constituents. Establishing pH, doses, or amounts of constituents is not patentable. In re Aller, 105 USPQ 232, 232; 220F. 2d 454, 456 (CCPA, 1955). “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges”. In re Aller, 105 USPQ 232, 235 (CCPA, 1955), In re Russel, 169 USPQ 426, 439 F2d 1228 (CCPA, 1971).
Claims 15, 16, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Towner (WO 2017/0027891; Publication Date: 2 February 2017) in view of Maderuelo (European Journal of Pharmaceutical Sciences, 138, 2019).
As described above, Towner teaches the use of 2,4-ds-PBN in the treatment of gliomas, as well as oral dosage forms of this compound.
Towner fails to teach a composition wherein the composition comprises at least one coating layer which solubilizes at a predetermined range of pH.
Maderuelo, as described previously, teaches the use of enteric coating of oral pharmaceutical formulations, and describes the benefits of this technique.
Towner and Maderuelo are considered analogous to the claimed invention as all are involved in the development of oral formulations of pharmaceuticals. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply an enteric coating, as taught by Madeuelo, to the oral formulations of 2,4-ds-PBN of Towner. Enteric coating to protect oral formulations from degradation in the stomach is commonly used in the pharmaceutical arts, and as Maderuelo teaches, is used to guarantee the stability of the drug and protect the gastric mucosa against irritation. The use of enteric coating on the formulations of Towner is prima facie application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)), wherein the known technique is enteric coating of oral formulations, as described by Maderuelo, applied to the known oral formulations of Towner, predictably resulting in an oral formulation that will solubilize at a pre-determined range of pH values. Claims 15 and 21 are written as “intended use” claims, and as such, this composition anticipates the claimed usage as the intended use of the claimed invention does not result in a structural difference between the claimed invention and the prior art (See MPEP § 2122.2 (II)). The range of dosages described by Towner (5 to 150 mg/kg body weight per day) falls within the claimed dosage range of 5 mg/kg body weight to 1,000 mg/kg body weight. The composition of Towner has doses or amounts of constituents. Establishing pH, doses, or amounts of constituents is not patentable. In re Aller, 105 USPQ 232, 232; 220F. 2d 454, 456 (CCPA, 1955). “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges”. In re Aller, 105 USPQ 232, 235 (CCPA, 1955), In re Russel, 169 USPQ 426, 439 F2d 1228 (CCPA, 1971).
Conclusion
Claims 1, 3-12, 14-16, and 19-21 are rejected.
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 PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625