DETAILED ACTION
Claim Interpretation
BRI of the following claim terms is according to the definitions in the original specification:
therapeutically effective at p. 23, lines 12-27;
bolus at p. 23, lines 28-30;
a C-type natriuretic peptide or CNP at p. 24, lines 18-24;
a long acting CNP at p. 25, lines 8-25;
a very long acting CNP at p. 25, line 26 – p. 35, line 11;
a long acting CNP derivative at p. 26, line 12 – p. 27, line 6;
a very long acting CNP derivative at p. 27, line 7 – p. 28, line 2;
a NPRB agonist at p. 28, lines 7-15;
a long acting NPRB agonist at p. 28 lines 16-32;
a very long acting NPRB agonist at p. 29, lines 1-21;
treatment at p. 33, lines 28-29.
Claim Objections
Claims 21 and 27 are objected to because of the following informalities:
The amendment to claim 21 reads “wherein the subject has ALI is associated with…”. The grammatical issue can be resolved by inserting --and the ALI-- after “ALI”.
To properly depend from claim 1, claim 27 should be amended to include the word --is-- prior to each “caused” in the claim.
Appropriate correction is required.
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.
All rejections under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in view of the amendment filed May 18, 2026, except for the following.
Claim 20 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for subcutaneous, intravenous, and intramuscular administration, does not reasonably provide enablement for inhalation, nasal, or oral administration. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
This rejection can be overcome by deleting “nasal, by inhalation, enteral,” and
“, or
wherein the route of administration is subcutaneous; or
wherein the route of administration is intravenous; or
wherein the route of administration is intramuscular; or
wherein the route of administration is by inhalation; or
wherein the route of administration is nasal; or
wherein the enteral route of administration is oral” from claim 20.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
All rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendment filed May 18, 2026, except for the following.
Claims 1, 18, 20-21, 24, 27, 30, 35, 45, and 64-65 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims are indefinite because the structure of SEQ ID NO: 6 is ambiguous. SEQ ID NO: 6 is presented in the claims as:
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The definition of “CNP” on page 24, lines 18-24 of the specification states that a CNP has a 17 amino acid residue ring structure formed by a disulfide bond, and an additional 5 amino acid residue extension (Cys6 and Cys22 are linked by a disulfide bond). However, neither the claims nor the sequence listing require the disulfide bond. It is not clear whether the absence of the disulfide bond is an intentional modification of the CNP to a CNP derivative, or whether the disulfide is included based on the definition in the specification of CNP. Because of the alternative constructions, the structure of the long acting CNP derivative, even those that appear to be fully definite like SEQ ID NO: 6, are indefinite.
This rejection can be overcome by inserting --wherein the peptide includes a disulfide bond between the cysteine residues-- after [SEQ ID NO: 6] each time it appears in the claims.
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 following rejections have been modified to reflect the amendment filed May 18, 2026.
Claims 1, 18, 20-21, 24, 27, 30, 35, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Kimura et al. (Protective Effect of C-Type Natriuretic Peptide on Lipopolysaccharide-Induced Acute Lung Injury In Mice, Interactive CardioVascular and Thoracic Surgery, Volume 18, Issue suppl_1, June 2014, Page S53; hereafter “Kimura 2014”), and Kimura et al. (Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in Mice. Cancer Chemother Pharmacol 75, 1057–1063 (2015); hereafter “Kimura 2015”) in view of Castillo et al. (WO 2018/175534 A1).
Determining the scope and contents of the prior art.
Kimura 2014 teaches that C-type natriuretic peptide (CNP) had a protective effect on LPS-induced ALI mice accompanied by reducing the infiltration of inflammatory cells. CNP significantly attenuated the elevation of total cell counts and cytokine levels such as monocyte chemoattractant protein-1, tumour necrosis factor-alpha, interleukin-6, chemokine ligand 1, and macrophage inflammatory protein-2 in the BALF of mice after LPS injection. In addition, there were significantly fewer MPO-positive cells in the lung of CNP-treated mice than in control mice. Kimura 2014 teaches that CNP may be of value in prophylactic strategies for ALI following pulmonary resection surgery. See abstract.
Kimura 2015 teaches CNP inhibits nephrotoxicity and kidney cell damage induced by cisplatin. The mechanism of action may involve down-regulation of inflammatory cytokine expression in cisplatin-induced kidney injury and attenuation of apoptosis in renal tubular cells. CNP (2.5 μg/kg/min, subcutaneous reduced histological renal tubular damage and apoptosis induced by cisplatin and suppressed plasma blood urea nitrogen and creatinine levels, which were elevated by cisplatin administration. CNP treatment decreased the expression of kidney injury molecule-1 and monocyte chemoattractant protein-1, which were elevated in the kidney by cisplatin administration. CNP treatment attenuated the decrease in GC-B expression in cisplatin-induced kidney injury. See abstract.
Ascertaining the differences between the prior art and the claims at issue.
Neither Kimura 2014 not Kimura 2015 teach: 1) bolus administration, 2) that the CNP is SEQ ID NO: 6.
Resolving the level of ordinary skill in the pertinent art.
It is within the ordinary level of skill in the pertinent art to use long-acting and very long-acting CNPs, such as SEQ ID NO: 6, for therapeutic applications.
Castillo et al. teach that natriuretic peptides increase cyclic guanosine monophosphate (cyclic-GMP) and can be used to treat a variety of vascular and cardiovascular diseases and conditions (p. 1). Castillo et al. identified a problem in the prior art: medicinal use of natriuretic peptides including C-type natriuretic peptide (CNP) is limited by their short half-life, limited activity to provide sufficient cyclic-GMP, and requirement for continuous intravenous administration (p. 2, lines 2-5). To solve this problem, Castillo et al. developed natriuretic peptides with extended half-lives and enhanced activity as measured by an increase in cyclic-GMP (p. lines 24-27). The natriuretic peptides can be administered by parenteral routes, including subcutaneous bolus administration (p. 3, lines 16-23; Example 1).
Castillo et al. teach a long-acting CNP with the structure CH3(CH2)16COKKKKGGGGLSKGCFGLKLDRIGSMSGLGC (compound CNP 72; p. 42), which is identical to instant SEQ ID NO: 6.
Castillo et al. teach that this compound has “unexpectedly increased potency” and “prevented apparent receptor depletion/internalization” (p. 39, lines 1-9). The CNP 72 (instant SEQ ID NO: 6) has the highest level of activity at 2 hours and 6 hours compared to hCNP (compound 57) of the derivatives tested by Castillo et al. (see data on p. 42; the activity columns show data at 2 hours and 6 hours)
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Castillo et al. teach a method of increasing blood cGMP in a patient comprising parenterally or subcutaneously administering the natriuretic peptide at a dose of less than 1.5 mg/kg/day of body weight in a pharmaceutically acceptable carrier or excipient (p. 28, lines 8-20). Single injections were reduced to practice, which constitutes a bolus dose (Example 1, p. 35, lines 8-10).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The results presented in the specification are expected in view of the cited references.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute bolus administration of the long-acting CNP identical to instant SEQ ID NO: 6 taught by Castillo et al. for the CNP in the method of treating LPS-induced ALI taught by Kimura 2014 or for the CNP in the method of treating cisplatin-induced kidney injury taught by Kimura 2015. The rationale for obviousness is simple substitution of one known element for another to obtain predictable results (MPEP § 2143.01(B)). The relevant findings for this rationale are as follows.
(1) The prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components. In the instant case, the primary references of Kimura 2014 and Kimura 2015 teach a method of which differs from the claimed method by the substitution of continuous administration of CNP with bolus administration of long-acting CNP SEQ ID NO: 6. Therefore, prior art contained a method which differed from the claimed device by the substitution of some step with other steps.
(2) The substituted components and their functions were known in the art. Castillo et al. teach SEQ ID NO: 6 and its administration to a subject by a bolus dose, which is the substituted component. The function of SEQ ID NO: 6 is known in the art because Castillo et al. teach that this compound has “unexpectedly increased potency” and “prevented apparent receptor depletion/internalization” (p. 39, lines 1-9). Castillo et al. provide a direct comparison between CNP (compound 57 in Castillo et al.) and SEQ ID NO: 6 (compound 72 in Castillo et al.): SEQ ID NO: 6 has significantly increased potency at 2 hours as well as at 6 hours (p. 42, Table reproduced above). Therefore, the substituted components and their functions were known in the art.
(3) One of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. One of ordinary skill in the art would expect that the long-acting CNP SEQ ID NO: 6 performs the function of elevating intracellular cyclic-GMP in the combination because Castillo et al. demonstrate by direct comparison to CNP that SEQ ID NO: 6 has this function in vivo and in fact has enhanced potency relative to hCNP-22. The CNP and SEQ ID NO: 6 (compound CNP 72 of Castillo et al.) share the same core CNP sequence. SEQ ID NO: 6 (compound CNP 72) is modified at the N-terminus with an amino acid sequence KKKKGGG and a fatty acid CH3(CH2)16C=O. The N-terminal modification with the CH3(CH2)16C=O KKKKGGG is responsible for the increased potency, extended activity, and suitability for bolus administration. In view of the data from a direct comparison provided by Castillo et al., one of ordinary skill in the art would have a reasonable expectation that SEQ ID NO: 6 (compound CNP 72) would be effective in the method of treating LPS-induced ALI taught by Kimura 2014 and in the method of treating cisplatin-induced kidney injury taught by Kimura 2015. In addition, one of ordinary skill in the art would expect based on the direct comparison and the reduction to practice in Castillo et al. that the SEQ ID NO: 6 (compound CNP 72) would have the benefit of being long-acting and being suitable for bolus administration. Therefore, one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable.
(4) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The specification does not provide evidence of unexpected results sufficient to overcome the prima facie case.
The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. Therefore, claims 1, 18, and 35 are obvious over the cited art.
Regarding claim 20, Castillo et al. teach bolus administration via a subcutaneous route (p. 3, lines 16-23; Example 1; p. 35, lines 8-10).
Regarding claims 21, 24, and 27, the LPS-induced ALI taught by Kimura 2014 is a model for ALI associated with sepsis and infectious disease.
Claims 64-65 are rejected under 35 U.S.C. 103 as being unpatentable over Kimura et al. (Protective Effect of C-Type Natriuretic Peptide on Lipopolysaccharide-Induced Acute Lung Injury In Mice, Interactive CardioVascular and Thoracic Surgery, Volume 18, Issue suppl_1, June 2014, Page S53; hereafter “Kimura 2014”), and Kimura et al. (Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in Mice. Cancer Chemother Pharmacol 75, 1057–1063 (2015); hereafter “Kimura 2015”) in view of Castillo et al. (WO 2018/175534 A1), as applied to claims 1, 18, 20-21, 24, 27, 30, 35, and 45 above in further view of Bogdanov et al. (Protected Graft Copolymer (PGC) in Imaging and Therapy: A Platform for the Delivery of Covalently and Non-Covalently Bound Drugs. Theranostics. 2012;2(6):553-76) and Castillo et al. (Extending Residence Time and Stability of Peptides by Protected Graft Copolymer (PGC) Excipient: GLP-1 Example. Pharm Res (2012) 29:306–318; cited by Applicant).
Neither Kanagawa et al. nor Castillo et al. (WO 2018/175534 A1) teach that the long-acting CNP is combined with a polymer excipient comprising a poly(amino acid) grafted with PEG, fatty acid, anionic moieties, or any combination thereof.
Bogdanov et al. teach the family of protected graft copolymers (PGC) is based on a conjugate of polylysine backbone to which methoxypoly(ethylene glycol) (MPEG) chains are covalently linked in a random fashion via N-[Symbol font/0x65]-amino groups PGC is capable of long circulation times after injection into the blood stream. Bogdanov et al. teach that the PGC can bind natriuretic peptides and be used to deliver natriuretic peptides and extend their half-life (Section 5.3.2).
Castillo et al. teach a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty acid at the epsilon amino groups (abstract). Castillo et al. that the PGC can bind the peptide GLP1 and can be used to deliver GLP1 and extend its half-life (abstract).
It would have been obvious to improve the half-life of the CNPs taught by Kanagawa et al. and Castillo et al. (WO 2018/175534 A1), including SEQ ID NO: 6 (aka compound 72) by combining it with the PGC excipients taught by Bogdanov et al. and Castillo et al. The resulting compositions would satisfy all of the limitations of claims 64-65 because the references teach that the poly(amino acid) polylysine is grafted with MPEG and a fatty acid, and that the excipient binds to the peptide for delivery and half-life extension. One of ordinary skill in the art would have been motivated to do so because Bgdanov et al. and Castillo et al. teach that PGC excipients are a solution to the problem of short half-lives that limit the use of the peptide drugs and that Castillo et al. (WO 2018/175534 A1) teach that this is a problem for CNP in particular (p. 2, lines 2-5). There would have been a reasonable expectation of success given that Bogdanov et al. teach that the PGC can bind natriuretic peptides and be used to deliver natriuretic peptides and extend their half-life (Section 5.3.2).
Claims 1, 18, 20, 30, and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Bae et al. (C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis and inflammation in non-alcoholic steatohepatitis. Life Sciences 209 (2018) 349-356) in view of Castillo et al. (WO 2018/175534 A1).
Determining the scope and contents of the prior art.
Bae et al. teaches that CNP has anti-fibrotic and anti-inflammatory effects in the liver during HFD-induced NASH in mice (abstract).
Ascertaining the differences between the prior art and the claims at issue.
Bae et al. does not teach bolus administration of the CNP SEQ ID NO: 6.
Resolving the level of ordinary skill in the pertinent art.
It is within the ordinary level of skill in the pertinent art to use long-acting and very long-acting CNPs, such as SEQ ID NO: 6, for therapeutic applications.
Castillo et al. teach that natriuretic peptides increase cyclic guanosine monophosphate (cyclic-GMP) and can be used to treat a variety of vascular and cardiovascular diseases and conditions (p. 1). Castillo et al. identified a problem in the prior art: medicinal use of natriuretic peptides including C-type natriuretic peptide (CNP) is limited by their short half-life, limited activity to provide sufficient cyclic-GMP, and requirement for continuous intravenous administration (p. 2, lines 2-5). To solve this problem, Castillo et al. developed natriuretic peptides with extended half-lives and enhanced activity as measured by an increase in cyclic-GMP (p. lines 24-27). The natriuretic peptides can be administered by parenteral routes, including subcutaneous bolus administration (p. 3, lines 16-23; Example 1).
Castillo et al. teach a long-acting CNP with the structure CH3(CH2)16COKKKKGGGGLSKGCFGLKLDRIGSMSGLGC (compound CNP 72; p. 42), which is identical to instant SEQ ID NO: 6.
Castillo et al. teach that this compound has “unexpectedly increased potency” and “prevented apparent receptor depletion/internalization” (p. 39, lines 1-9). The CNP 72 (instant SEQ ID NO: 6) has the highest level of activity at 2 hours and 6 hours compared to hCNP (compound 57) of the derivatives tested by Castillo et al. (see data on p. 42; the activity columns show data at 2 hours and 6 hours)
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Castillo et al. teach a method of increasing blood cGMP in a patient comprising parenterally or subcutaneously administering the natriuretic peptide at a dose of less than 1.5 mg/kg/day of body weight in a pharmaceutically acceptable carrier or excipient (p. 28, lines 8-20). Single injections were reduced to practice, which constitutes a bolus dose (Example 1, p. 35, lines 8-10).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The results presented in the specification are expected in view of the cited references.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute bolus administration of the long-acting CNP identical to instant SEQ ID NO: 6 taught by Castillo et al. for the CNP in the method of inducing anti-fibrotic and anti-inflammatory effects in NASH taught by Bae et al. The rationale for obviousness is simple substitution of one known element for another to obtain predictable results (MPEP § 2143.01(B)). The relevant findings for this rationale are as follows.
(1) The prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components. In the instant case, the primary reference of Bae et al. teach a method of which differs from the claimed method by the substitution of overexpression of CNP with bolus administration of long-acting CNP SEQ ID NO: 6. Therefore, prior art contained a method which differed from the claimed device by the substitution of some step with other steps.
(2) The substituted components and their functions were known in the art. Castillo et al. teach SEQ ID NO: 6 and its administration to a subject by a bolus dose, which is the substituted component. The function of SEQ ID NO: 6 is known in the art because Castillo et al. teach that this compound has “unexpectedly increased potency” and “prevented apparent receptor depletion/internalization” (p. 39, lines 1-9). Castillo et al. provide a direct comparison between CNP (compound 57 in Castillo et al.) and SEQ ID NO: 6 (compound 72 in Castillo et al.): SEQ ID NO: 6 has significantly increased potency at 2 hours as well as at 6 hours (p. 42, Table reproduced above). Therefore, the substituted components and their functions were known in the art.
(3) One of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. One of ordinary skill in the art would expect that the long-acting CNP SEQ ID NO: 6 performs the function of elevating intracellular cyclic-GMP in the combination because Castillo et al. demonstrate by direct comparison to CNP that SEQ ID NO: 6 has this function in vivo and in fact has enhanced potency relative to hCNP-22. The CNP and SEQ ID NO: 6 (compound CNP 72 of Castillo et al.) share the same core CNP sequence. SEQ ID NO: 6 (compound CNP 72) is modified at the N-terminus with an amino acid sequence KKKKGGG and a fatty acid CH3(CH2)16C=O. The N-terminal modification with the CH3(CH2)16C=O KKKKGGG is responsible for the increased potency, extended activity, and suitability for bolus administration. In view of the data from a direct comparison provided by Castillo et al., one of ordinary skill in the art would have a reasonable expectation that SEQ ID NO: 6 (compound CNP 72) would be effective in the method of inducing anti-fibrotic and anti-inflammatory effects in NASH as taught by Bae et al. In addition, one of ordinary skill in the art would expect based on the direct comparison and the reduction to practice in Castillo et al. that the SEQ ID NO: 6 (compound CNP 72) would have the benefit of being long-acting and being suitable for bolus administration. Therefore, one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable.
(4) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The specification does not provide evidence of unexpected results sufficient to overcome the prima facie case.
The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. Therefore, claims 1, 18, and 66 are obvious over the cited art.
Regarding claim 20, Castillo et al. teach bolus administration via a subcutaneous route (p. 3, lines 16-23; Example 1; p. 35, lines 8-10).
35 USC § 103 - Response to Arguments
Applicant's arguments filed May 18, 2026, have been fully considered but they are not persuasive.
Applicant argues that a prima facie case has not been established because the combination of references fails to establish a reasonable expectation of success. Applicant argues that none of the cited references disclose experimental data showing that SEQ ID NO: 6 has efficacy in a model of lung, liver, and/or kidney injury. This argument is not persuasive because if any single reference taught that SEQ ID NO: 6 has efficacy in a model of lung, liver, and/or kidney injury an anticipation rejection would have been made. 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).
Applicant points to evidence in the specification in which bolus administration of SEQ ID NO: 6 is more effective than bolus administration of CNP in animal models of ALI, kidney injury, and liver fibrosis. Applicant correctly points out that specification provides a comparison between a bolus dose of hCNP-22, SEQ ID NO: 6, and the derivative of SEQ ID NO: 6 formulated with polylysine grafted with polyethylene glycol in animal models of ALI, kidney injury, and liver fibrosis and that the results show that a bolus dose of SEQ ID NO: 6 is effective in these models. This evidence is acknowledged but is not persuasive to overcome the rejection.
MPEP 716.02(b) states: The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992).
The data in the specification show that long-acting CNP SEQ ID NO: 6 and the very long-acting CNP SEQ ID NO: 6 formulated with polylysine grafted with polyethylene glycol are more effective than a bolus dose of unmodified CNP. However, Applicant has not shown how these data are unexpected in view of the prior art, namely the comparison in Castillo et al. showing that SEQ ID NO: 6 has enhanced potency relative to hCNP-22. Castillo et al. teach that hCNP-22 has a short half-life, and requires continuous, not bolus, intravenous administration (p. 2, lines 2-5). In contrast, Castillo et al. teach CNPs with extended half-lives and enhanced activity, including SEQ ID NO: 6 (p. lines 24-27). Because of this reported activity and property, Castillo et al. teach that SEQ ID NO: 6, unlike hCNP-22, can be administered by parenteral routes, including subcutaneous bolus administration (p. 3, lines 16-23; Example 1). Therefore, one of ordinary skill in the art would expect the SEQ ID NO: 6 and its derivative to be superior in comparison to a bolus dose of hCNP-22 in the Example 15 of the specification. Although the other references disclose continuous administration, Castillo et al. is directed to solving this problem and using bolus administration as an improvement. The evidence relied upon to overcome the rejected is expected, not unexpected in view of the art, and therefore insufficient to overcome the prima facie case.
Applicant points to evidence in the specification in which bolus administration of SEQ ID NO: 6 is more effective than bolus administration of CNP in animal models of IPF. Applicant correctly points out that specification provides a comparison between a bolus dose of hCNP-22, SEQ ID NO: 6, and the derivative of SEQ ID NO: 6 formulated with polylysine grafted with polyethylene glycol in animal models of IPF and that the results show that a bolus dose of SEQ ID NO: 6 is effective in these models. This evidence is acknowledged but is not persuasive to overcome the rejection because the result is not commensurate with the full scope of the claims, which include treatment of other conditions disclosed by the prior art (MPEP 716.02(d)).
For these reasons, the rejection is maintained.
Conclusion
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 CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
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