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 .
Any rejection or objection from the previous office action, which is not restated here, is withdrawn.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 31, 2023, has been entered.
Election/Restrictions
Applicant’s election of Group I (i.e., claims 1-17 drawn to a cyclic peptide having an amino acid sequence expressed by the formula I) in the reply filed on May 22, 2019, is acknowledged. Additionally, Applicant’s election of Species A (i.e., a single and specific cyclic peptide as SEQ ID NO: 63); and Species B (i.e., a single and specific use as a medicament, a quasi-drug and cosmetic product) in the reply filed on May 22, 2019, is acknowledged. However, as indicated in the accompanying interview summary, both species would be considered incomplete because SEQ ID NO: 63 comprises variable residues and because the elected use does not constitute a single and specific use. As such, Applicant’s election of Species A (i.e., a single and specific cyclic peptide as SEQ ID NO: 63); and Species B (i.e., a single and specific use as a medicament, a quasi-drug and cosmetic product) in the interview held on August 15, 2019, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
However, please note that in light of the Examiner’s search, the scope of Species A is expanded to include a derivative of SEQ ID NO: 3. As such, instant claim 5 is hereby rejoined and examined.
Additionally, as indicated in the Restriction Requirement mailed on March 22, 2019, the grouping of the claims would need to be modified depending on the amendment to claim 18 (note: claim 18 was omitted from the groupings because it did not recite a recognized statutory class of invention). Accordingly, the groupings are modified as follows:
Group I, claims 1-17 and 27-28, drawn to a cyclic peptide having an amino acid sequence of formula I, an external preparation comprising one or more cyclic peptides, and a medicament comprising one or more cyclic peptides.
Group II, claim 18, drawn to a method of manufacturing a topical agent comprising combining the cyclic peptide of claim 1 with a constituent of an external preparation.
Group III, claims 19-26, drawn to a method of using the external preparation comprising applying the external preparation to skin and/or mucosa of a subject.
It is noted that the updated Groups lack unity of invention for the reasons stated in the Restriction Requirement mailed on March 22, 2019.
Status of Claims
Claims 1-28 were originally filed on January 31, 2018.
The amendment received on June 25, 2018, amended claims 5-7, 9-10, 15-19, 25, and 27. The amendment received on May 22, 2019, amended claims 1, 17-18, and 20-26. The amendment received on December 23, 2019, amended claims 1, 5, 8, 10, and 16-17. The amendment received on September 30, 2020, canceled claims 2-4, 6, 11-14, and 18-26; amended claim 1; and added new claims 29-36. The amendment received on September 30, 2021, amended claims 1 and 36. The amendment received on April 15, 2022, amended claim 9. The amendment received on May 31, 2023, amended claim 1.
Claims 1, 5, 7-10, 15-17, and 27-36 are currently pending and claims 1, 5, 7-10, 15-17, 27, and 32-36 are under consideration as claims 2-4, 6, 11-14, and 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, and claims 18-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 22, 2019.
Priority
The present application claims status as a 371 (National Stage) of PCT/JP2016/072562 filed August 1, 2016, and claims priority under 119(a)-(d) to Japanese Application No. 2015/152722 filed on July 31, 2015.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Japanese Application No. 2015/152722, which papers have been placed of record in the file. Please note that the Japanese application is in Japanese and therefore cannot be verified.
Sequence Interpretation
Please note that the Examiner is interpreting the scope of claim 1 as closed-ended requiring 100% identity and the same length to SEQ ID NO: 63. As such, the claimed cyclic peptide does not encompass any N-/C-terminal additions. Moreover, by requiring that the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence preclude where additional residues are inserted or deleted within the amino acid sequence. However, the claimed cyclic peptide does encompass a derivative thereof but the derivative cannot include additional amino acid residues at the N-/C-terminals and/or modifications of the peptide bonds. Thus, the scope of claim 1 is analogous to “consisting of SEQ ID NO: 1” above.
Maintained/Modified Rejections in light of Applicants’ Amendments
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) 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. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary 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.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 5, 7-9, 15-17, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Golembo et al. U.S. Patent No. 7,276,481 B2 issued on 10/2/07 at Fig. 3C (cited in the IDS received on 5/22/19), alone or as evidenced by, Merriam-Webster, “Medicament”, available online at https://www.merriam-webster.com/dictionary/medicament, 11 pages (accessed on 8/12/19) (hereinafter the “Merriam-Webster” reference). Please note that the rejection has been updated in light of Applicant’s amendment to claim 1.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claim 1, with respect to a cyclic peptide consisting of an amino acid sequence expressed by the Formula I wherein X1 is Gly, X2 can be Leu or Ala, X3 is Val, X4 can be Ser, Ala or Thr, X5 is Ser, and X6 can be Leu or Met thereby resulting in SEQ ID NO: 63 where the two cysteine residues are linked via a disulfide bond and where the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence:
Golembo et al. teaches a pharmaceutical composition comprising natriuretic peptides (NP) wherein the NP includes a CNP (See Golembo specification, col. 4, lines 8-11; col. 5, lines 25-32). In particular Golembo et al. examined CNP analog sequences of a shortened CNP 5-22 peptide (i.e., SEQ ID NO: 2) which was shown to be active in cGMP assay (See Golembo specification, col. 14, lines 41-46). Table 3 depicts additional 17mer variants that were synthesized and tested for activation of cGMP by determining the percent binding (See Golembo specification, col. 15, lines 50-55; col. 16, lines 50-55). SEQ ID NO: 52 is a specific CNP analog sequence where Ile at position 13 (i.e., corresponds to instant X3) is substituted from Ile to Val (See Golembo specification, Table 3). As such, when comparing Golembo’s SEQ ID NO: 52 with instant SEQ ID NO: 63, there is 100% identity where X1 is Gly, X2 can be Leu, X3 is Val, X4 can be Ser, X5 is Ser, and X6 is Leu.
Moreover, it is noted that Golembo’s SEQ ID NO: 52 is 17 amino acids in length thereby constituting where the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence. Moreover, Golembo et al. teaches that a disulfide bond exists between the N- and C-terminal cysteine residues and there are no peptide bonds other than between the amino acids in the amino acid sequence given that these CNP variant sequences are based on the shortened CNP 5-22 fragment as depicted in Figure 3, which contains a disulfide bond (See Golembo specification, Fig. 3; col. 14, lines 42-49). Therefore, the teachings of Golembo et al. satisfy the claim limitations with respect to a cyclic peptide consisting of an amino acid sequence expressed by the Formula I wherein X1 is Gly, X2 can be Leu or Ala, X3 is Val, X4 can be Ser, Ala or Thr, X5 is Ser, and X6 can be Leu or Met thereby resulting in SEQ ID NO: 63 where the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence as recited in instant claim 1.
For claim 1, with respect to where for at least of X1-X6: X1 does not denote Gly, X2 doe not denote Leu, X3 does not denote Ile, X4 does not denote Ser, X5 does not denote Ser, and X6 does not denote Leu:
Golembo’s SEQ ID NO: 52 does not denote Ile at the position corresponding to instant X3. However, Golembo’s SEQ ID NO: 52 does not expressly denote where one of X1-X2 or X4-X6 are not on the identified residues in claim 1.
Additional specific CNP analog sequences (i.e., SEQ ID NOs: 45-47 for instant X2 substitutions, SEQ ID NOs: 54-57 for instant X4 substitutions and SEQ ID NOs: 61-64 for instant X6 substitutions) examined by Golembo include where the Leu at position 10 (i.e., correspond to instant X2) is substituted to Ala, Ile, and Val; the Ser at position 15 (i.e., corresponds to instant X4) is substituted to Ala, Gly, Thr, and Asn; and where the Leu at position 20 (i.e., corresponds to instant X6) is substituted to Gln, Met, Ala, and Gly (See Golembo specification, Table 3). It is noted that one of the three substitutions at X2 are encompassed by instant X2 (i.e., Ala), two of the four substitutions at X4 are encompassed by instant X4 (i.e., Ala and Thr), and two of the four substitutions at X6 are encompassed by instant X6 (i.e., Met and Ala). It is further noted that Golembo’s SEQ ID NO: 52 exhibited a relative binding percentage of about 27%, SEQ ID NOs: 45-47 exhibited a relative binding percentage of about 11%, 88%, and 66%, SEQ ID NOs: 54-57 exhibited a relative binding percentage of about 54%, 27%, 74%, and 27%, respectively, and SEQ ID NOs: 61-64 exhibited a relative binding percentage of about -3.4%, 51%, -1%, and -10%, respectively (See Golembo specification, Table 3). Moreover, Golembo et al. teaches that SEQ ID NOs: 45-47 and 54-57 included modifications directed to cleavage sites and maintained activity (See Golembo specification, Table 3; col. 19, lines 42-47). Golembo’s SEQ ID NO: 56, which contains a substitution at instant X4 from Ser to Thr, exhibits the second highest binding activity percentage compared to any other CNP analog sequences in Table 3 (See Golembo specification, Table 3). Therefore, with respect to instant X2 or X4, as will be further articulated below, an ordinary skilled artisan would be motivated with a reasonable expectation of success to modify Golembo’s SEQ ID NO: 52 with an additional substitution at the position corresponding to instant X2 from Leu to Ala, or X4 from Ser to Ala or Thr, and in particular Thr, given that each of these substitutions reduced degradation of the CNP analog sequence (i.e., an ordinary skilled artisan would expect a substitution at a cleavage site to improve degradation of the resulting sequence) and maintained activity to bind to cGMP, especially since the Ser to Thr substitution maintained relatively high activity.
Similarly, with respect to instant X6, the only substitution that maintained binding to cGMP is the substitution from Leu to Met (i.e., 51%). Therefore, as will be further articulated below, an ordinary skilled artisan would motivated to, at a minimum, to try with a reasonable expectation of success to modify Golembo’s SEQ ID NO: 52 with an additional substitution at the position corresponding to instant X6 from Leu to Met to improve binding to cGMP given that only a finite number of substitutions at instant X6, i.e., Leu to Met, resulted in maintained binding efficiency to cGMP. Thus, the teachings of Golembo suggest the claim limitation with respect to where for at least of X1-X6: X1 does not denote Gly, X2 do not denote Leu, X3 does not denote Ile, X4 does not denote Ser, X5 does not denote Ser, and X6 does not denote Leu as recited in instant claim 1.
For claim 5, with respect to where a derivative of SEQ ID NO: 63 is substituted by a substituent which is capable of replacing an amino group, hydrogen atom, or carboxyl group in the cyclic peptide:
Golembo et al. teaches that the CNP analogs may be modified by incorporation of a reporter molecule that allows detection such as a biotin or fluorescein, at either the N-terminus or C-terminus of the peptide (See Golembo specification, col. 14, lines 64-67). Thus, the teachings of Golembo et al. suggest modifying the N-terminus or C-terminus of the cyclic peptide thereby necessarily encompassing where a hydrogen atom, carboxyl group (i.e., C-terminus), or amino group (i.e., N-terminus) of the cyclic peptide is substituted with a reporter molecule such as a biotin or fluorescein as recited in instant claim 5.
For claim 7, with respect to an external preparation comprising one or more cyclic peptides of claim 1:
Golembo et al. teaches pharmaceutical compositions and medicament formulations comprising the NP in combination with a pharmaceutically acceptable carrier (See Golembo specification, col. 7, lines 39-59). Moreover, Golembo et al. teaches that the pharmaceutical composition include those suitable for intra-articular, intravenous, intramuscular, subcutaneous, intradermal, intrathecal, intranasal, oral, or topical administration (See Golembo specification, col. 8, lines 5-18; col. 9, lines 13-63). Plus, Golembo et al. teaches that the drug is absorbed through the mucous membrane when administered as an intranasal spray (See Golembo specification, col. 8, lines 14-18). It is noted that the instant specification defines an “external preparation” as an agent that is applied to skin and/or mucosa (See instant specification, paragraph [0062]). As such, intranasal and topical administration taught by Golembo et al. constitute an external preparation. Thus, the teachings of Golembo et al. satisfy the claim limitation as recited in instant claim 7.
For claims 8-9, with respect to where the one or more cyclic peptides is an ingredient for a therapeutic for a skin-care product as recited in instant claim 8; and with respect to where the skin-care product is for preventing/improving dry skin as recited in instant claim 9:
Golembo et al. teaches that the drug is absorbed through the mucous membrane when administered as an intranasal spray (See Golembo specification, col. 8, lines 14-18). Plus, Golembo et al. teaches that the pharmaceutical formulations administered topically are in the form of a gel, ointment, cream, emulsion, solid, or a sustained release formulation including a transdermal patch (See Golembo specification, col. 9, lines 55-63).
Additionally, although Golembo et al. does not teach that the NP is an ingredient for a skin-care product wherein the skin-care product is for improving dry skin, the Examiner would like to remind Applicants that the preamble recites an external preparation, and while the use of a descriptive clause, i.e. “an ingredient for a skin-care product” or “a skin-care product for improving dry skin” when referring to the contemplated use (i.e. “intended use”) of a claimed compound is proper, it is not a limitation and thus of no significance in determining the patentability thereof over the prior art, please refer to In re Thomas (CCPA 1949) 178 F2d 412, 84 USPQ 132. Therefore, the teachings of Golembo et al. satisfy the claim limitation as recited in instant claims 8-9 given that Golembo et al. teaches that the pharmaceutical formulations are suitable for intranasal or topical administration in the form of an intranasal spray, gel, ointment, cream, emulsion, solid, or a sustained release formulation including a transdermal patch.
Additionally and/or alternatively, although Golembo et al. does not teach that the NP is an ingredient for a skin-care product wherein the skin-care product is for improving dry skin, it is unnecessary for a prior art reference to teach the intended use of the external preparation because the intended use of the external preparation (i.e., ingredient for a skin-care product wherein the skin-care product is for improving dry skin) does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed external preparation. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the intended use of the external preparation (i.e., ingredient for a skin-care product wherein the skin-care product is for improving dry skin) is an intended result of the claimed external preparation that gives little meaning and purpose to the structure of the claimed external preparation. Accordingly, claims 8-9 recite an intended result that does not render material to patentability.
For claim 15, with respect to where the external preparation is a solid, semi-solid, powder, liquid, spray, ointment, cream, emulsion, gel or patch:
Golembo et al. teaches that the drug is absorbed through the mucous membrane when administered as an intranasal spray (See Golembo specification, col. 8, lines 14-18). Plus, Golembo et al. teaches that the pharmaceutical formulations administered topically are in the form of a gel, ointment, cream, emulsion, solid, or a sustained release formulation including a transdermal patch (See Golembo specification, col. 9, lines 55-63). Thus, the teachings of Golembo et al. satisfy the claim limitation as recited in instant claim 15.
For claim 16, with respect to where the external preparation comprises the cyclic peptide at a concentration from 0.0001 to 1000000 mcg/mL:
Golembo et al. teaches that the dose of the pharmaceutical composition comprising the NP may vary with the kind of disease, the age of patient, body weight, the severity of disease, the route of administration, etc.; typically, it can be administered in a daily dose of 0.5-500 mcg/kg (See Golembo specification, col. 7, lines 60-64). Assuming that water is an excipient in the claimed external preparation the density of water is 1 g/mL, the claimed concentration can be divided by 1 g/ml thereby resulting in a claimed range of 1 x 10-2 to 1 x 109 mcg/kg. As such, the taught dosage range of Golembo et al. falls within the claimed concentration range.
For claim 17, with respect to where the external preparation is formulated for use as a medicament, a quasi-drug or a cosmetic product:
Golembo et al. teaches pharmaceutical compositions and medicament formulations comprising the NP in combination with a pharmaceutically acceptable carrier (See Golembo specification, col. 7, lines 39-59). Golembo et al. also teaches that the NPs are prepared as medicaments useful in the treatment of various skeletal disorders (See Golembo specification, col. 10, lines 43-46). By administering the NPs to a subject for use in treating various skeletal disorders constitutes where the NP is an external preparation (See discussion of claim 7) that is formulated as a medicament. Thus, the teachings of Golembo et al. satisfies the claim limitation as recited in instant claim 17.
Additionally and/or alternatively, although Golembo et al. discloses that the NP is an external preparation (See discussion of claim 7) that is formulated as a medicament, the Examiner would like to remind Applicants that the preamble recites an external preparation, and while the use of a descriptive clause, i.e. “for use as a medicament,…” when referring to the contemplated use (i.e. “intended use”) of a claimed compound is proper, it is not a limitation and thus of no significance in determining the patentability thereof over the prior art, please refer to In re Thomas (CCPA 1949) 178 F2d 412, 84 USPQ 132. Therefore, the teachings of Golembo et al. satisfy the claim limitation as recited in instant claim 17.
Additionally and/or alternatively, although Golembo et al. teaches that the NP is an external preparation (See discussion of claim 7) that is formulated as a medicament, it is unnecessary for a prior art reference to teach the intended use of the external preparation because the intended use of the external preparation (i.e., for use as a medicament, a quasi-drug, or a cosmetic product) does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed external preparation. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the intended use of the external preparation (i.e., for use as a medicament, a quasi-drug, or a cosmetic product) is an intended result of the claimed external preparation that gives little meaning and purpose to the structure of the claimed external preparation. Accordingly, claim 17 recites an intended result that does not render material to patentability.
For claim 27, with respect to a medicament comprising one or more cyclic peptides of claim 1:
Golembo et al. teaches pharmaceutical compositions and medicament formulations comprising the NP in combination with a pharmaceutically acceptable carrier (See Golembo specification, col. 7, lines 39-59). Golembo et al. also teaches that the NPs are prepared as medicaments useful in the treatment of various skeletal disorders (See Golembo specification, col. 10, lines 43-46).
Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. As such, given that the instant specification does not define what is meant by a “medicament”, the plain and ordinary meaning of the word applies. “Medicament’ is defined as a substance used in therapy (See Merriam-Webster reference, pg. 2). Thus, by administering the NPs as a medicament useful in the treatment of various skeletal disorders constitutes where the NP is a medicament. Thus, the teachings of Golembo et al. satisfy the claim limitation as recited in instant claim 27.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Golembo et al. does not expressly teach a specific embodiment of a cyclic peptide consisting of amino acid sequence of SEQ ID NO: 63 as recited in instant claim 1. However, the teachings of Golembo et al. cure this deficiency by constituting 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 and/or utilizing the "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant under KSR.
Golembo et al. does not expressly teach a specific embodiment where a derivative of the cyclic peptide has been substituted with a substituent that is replaceable for the hydrogen atom, hydroxyl group, carboxyl group, or amino group in the cyclic peptide as recited in instant claim 5. However, the teachings of Golembo et al. cure this deficiency by constituting 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 pursuant under KSR.
Golembo et al. does not expressly teach a specific embodiment where the external preparation comprises the cyclic peptide at a concentration from 0.0001 to 1000000 mcg/mL as recited in instant claim 16. However, the taught dosage range of Golembo et al. lies within the claimed dosage range as further articulated below.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a cyclic peptide consisting of amino acid sequence of SEQ ID NO: 63 as recited in instant claim 1, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to follow the teachings of Golembo et al. and modify the cyclic peptide of SEQ ID NO: 52 with an additional substitution at the position corresponding to instant X4 from Ser to Ala or Thr, or X6 from Leu to Met thereby resulting in a CNP analog sequence with a substitution at the position corresponding to instant X3 from Ile to Val and to either instant X2 from Leu to Ala, instant X4 from Ser to Ala or Thr, or instant X6 from Leu to Met and thereby reducing protein degradation when the substitution is at the position corresponding to X2 or X4 and maintaining CNP activity. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because CNP variant peptides having a substitution at the position corresponding to X2 or X4 were known to exhibit improved stability by reducing degradation by NEP or NRP-C and maintained CNP activity, and because a CNP variant peptide having a substitution at the position corresponding to X6 from Leu to Met was known to maintain CNP activity as taught by Golembo et al.
One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the cyclic peptide of SEQ ID NO: 52 of Golembo et al. contained a substitution at the position corresponding to instant X3 from Ile to Val and maintained CNP binding activity to cGMP. Therefore, modifying Golembo’s SEQ ID NO: 52 with an additional substitution at the position corresponding to X2 or X4 such that Leu is substituted for Ala at instant X2 or Ser is substituted for Ala or Thr at instant X4 would support the improved stability of the CNP variant peptide by reducing protein degradation and the maintenance of CNP activity by constituting 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 pursuant under KSR.
Additionally and/or alternatively, one of ordinary skill in the art at the time the invention was made would be motivated to try with a reasonable expectation of success given that the cyclic peptide of SEQ ID NO: 52 of Golembo et al. contained a substitution at the position corresponding to instant X3 from Ile to Val and maintained CNP binding activity to cGMP. Therefore, modifying Golembo’s SEQ ID NO: 52 with an additional substitution at the position corresponding to X6 from Leu to Met in light of the finite number of substitutions taught at the position corresponding to X6 would support the maintenance of CNP activity by constituting the "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant under KSR.
With respect to where a derivative of the cyclic peptide has been substituted with a substituent that is replaceable for the hydrogen atom, hydroxyl group, carboxyl group, or amino group in the cyclic peptide as recited in instant claim 5, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to follow the teachings of Golembo et al. and modify the N- or C-terminus of the cyclic peptide with a reporter molecule such as biotin in order to allow for detection thereby resulting where a hydrogen atom, carboxyl group or amino group of the cyclic peptide is substituted. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because modifying the N-terminus or C-terminus of the cyclic peptide was known to allow for detection of the peptide as taught by Golembo et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the cyclic peptide of Golembo et al. was examined for activity by utilizing an enzyme immunoassay and therefore modifying the N-terminus or C-terminus with a reporter molecule such as biotin by substituting a hydrogen atom, carboxyl group or amino group of the cyclic peptide would support the detection of the cyclic peptide in the enzyme immunoassay by constituting 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 pursuant under KSR.
With respect to where the external preparation comprises the cyclic peptide at a concentration from 0.0001 to 1000000 mcg/mL as recited in instant claim 16, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed concentration range of the cyclic peptide in the external preparation would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 0.5 to 500 mcg/kg) lies within with the claimed concentration range of the cyclic peptide (i.e., 0.0001 to 1000000 mcg/mL).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 7, 10, 17, and 32-36 are rejected under 35 U.S.C. 103 as being unpatentable over Golembo et al. U.S. Patent No. 7,276,481 B2 issued on 10/2/07 (cited in the IDS received on 5/22/19), alone or as evidenced by, Merriam-Webster, “Medicament”, available online at https://www.merriam-webster.com/dictionary/medicament, 11 pages (accessed on 8/12/19) (hereinafter the “Merriam-Webster” reference), as applied to claims 1, 8, and 17 above, and further in view of Endo U.S. Publication No. 2012/0208756 A1 published on August 16, 2012 (cited in the IDS received on 5/22/19), as applied to claims 10 and 32-36 herewith.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 1, 7, and 17, please see discussion of Golembo et al. above.
For claims 10, 32-34, and 36, with respect to where the external preparation is a bathing agent, body cleansing agent, hair cleansing agent, hair rinse/treatment, hair tonic, hair oil, hair lotion, or scalp care agent as recited in instant claim 10; with respect to where the cosmetic product is a skin lotion, emulsion, cream, and facial mask as recited in instant claim 32; with respect to where the cosmetic product is a make-up cosmetic, hair cosmetic, body cleansing agent, or bathing agent as recited in instant claim 33; with respect to where the make-up cosmetic is a foundation cream or make-up base as recited in instant claim 34; and with respect to where the body cleansing agent is a cleanser as recited in instant claim 36:
Golembo et al. discloses that the drug is absorbed through the mucous membrane when administered as an intranasal spray (See Golembo specification, col. 8, lines 14-18). Plus, Golembo et al. discloses that the pharmaceutical formulations administered topically are in the form of a gel, ointment, cream, emulsion, solid, or a sustained release formulation including a transdermal patch (See Golembo specification, col. 9, lines 55-63).
Endo teaches a skin preparation composition comprising a CNP or BNP including CNP analogs (See Endo specification, paragraph [0060]-[0061], [0087]-[0090], [0098], [0106], [0108]-[0109]) where the composition is a skin texture-improving agent that is used for improving dry skin and is a skin care product and a skin care cosmetic product (See Endo specification, paragraph [0061], [0087]-[0090], [0116]). Endo teaches that when the skin external-preparation composition is to be used as a skin texture-improving agent, the preferred dosage forms include cream, foam, skin lotion, facial mask, skin-softening water, skin emulsion, foundation, makeup base, essence, soap, liquid cleanser, bath agent, sun-block cream, suntan oil or spray-type liquid preparation (See Endo specification paragraph [0061], [0116]). As such, the teachings of Endo suggest the external preparation being applied topically as a bathing agent or body cleansing agent as recited in instant claim 10; being used as a skin care cosmetic product that is a skin lotion, emulsion, cream, gel, or facial mask as recited in instant claim 32; being used as a skin care cosmetic product that is a make-up, body cleansing agent or bathing agent as recited in instant claim 33; being used as a skin care cosmetic product is a foundation cream or make-up base as recited in instant claim 34; and being used as a skin care cosmetic product that is a body cleansing agent and is a cleanser as recited in instant claim 36.
For claim 35, with respect to where the hair cosmetic is shampoo, hair rinse, conditioner, hair color, hair tonic, hair-set agent, or hair permanent agent as recited in instant claim 35:
Golembo et al. discloses that the drug is absorbed through the mucous membrane when administered as an intranasal spray (See Golembo specification, col. 8, lines 14-18). Plus, Golembo et al. discloses that the pharmaceutical formulations administered topically are in the form of a gel, ointment, cream, emulsion, solid, or a sustained release formulation including a transdermal patch (See Golembo specification, col. 9, lines 55-63).
Endo teaches a skin preparation composition comprising a CNP or BNP including CNP analogs (See Endo specification, paragraph [0060]-[0061], [0087]-[0090]) where the composition is a skin texture-improving agent that is used for improving dry skin and is a skin care product and a skin care cosmetic product (See Endo specification, paragraph [0061], [0087]-[0090], [0116]). Also, Endo teaches that a lotion preparation means a liquid external preparation where CNP is dissolved or homogenously dispersed in a liquid (See Endo specification, paragraph [0146]). Lotions are suitable for use on the head hair region, etc. where the form of lotions may be any of a suspension lotion base, an emulsion lotion, and a solution-type lotion base (See Endo specification, paragraph [0146]) thereby encompassing shampoo and/or conditioner. As such, the teachings of Endo suggest the external preparation being applied topically as a hair cosmetic product that is a shampoo and/or a conditioner as recited in instant claim 35.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Golembo et al. does not expressly teach where the external preparation is a bathing agent or body cleansing agent as recited in instant claim 10; where the cosmetic product is a skin lotion, emulsion, cream, and facial mask as recited in instant claim 32; where the cosmetic product is a make-up cosmetic, hair cosmetic, body cleansing agent, or bathing agent as recited in instant claim 33; where the make-up cosmetic is a foundation cream or make-up base as recited in instant claim 34; where the hair cosmetic is shampoo, hair rinse, conditioner, hair color, hair tonic, hair-set agent, or hair permanent agent as recited in instant claim 35; and where the body cleansing agent is a cleanser as recited in instant claim 36. However, the teachings of Endo cure this deficiency by constituting 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 and/or the use of known technique to improve similar devices (methods, or products) in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant under KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to where the external preparation is a bathing agent or body cleansing agent as recited in instant claim 10; where the cosmetic product is a skin lotion, emulsion, cream, and facial mask as recited in instant claim 32; where the cosmetic product is a make-up cosmetic, hair cosmetic, body cleansing agent, or bathing agent as recited in instant claim 33; where the make-up cosmetic is a foundation cream or make-up base as recited in instant claim 34; where the hair cosmetic is shampoo, hair rinse, conditioner, hair color, hair tonic, hair-set agent, or hair permanent agent as recited in instant claim 35; and where the body cleansing agent is a cleanser as recited in instant claim 36, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Golembo et al. and formulate the pharmaceutical composition comprising instant SEQ ID NO: 63 as described supra as an external preparation suitable for topical administration wherein the formulated external preparation is in the form of a bathing agent, body cleansing agent, skin lotion, emulsion, cream, gel, facial mask, a foundation cream, a make-up base, shampoo, conditioner, or a cleanser in order to improve dry skin on a subject as a skin care cosmetic product. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because a skin external-preparation composition comprising CNP-22 variants was known to be formulated as a skin care cosmetic product in the form of a bathing agent, body cleansing agent, skin lotion, emulsion, cream, gel, facial mask, a foundation cream, a make-up base, shampoo, conditioner, or a cleanser in order to improve dry skin as taught by Endo. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the cyclic peptide of Golembo et al. was formulated as an external preparation for topical administration as a gel, ointment, cream, emulsion, or solid and therefore formulating the external preparation for topical administration as a skin care cosmetic product in the form of a bathing agent, body cleansing agent, skin lotion, emulsion, cream, gel, facial mask, a foundation cream, a make-up base, shampoo, conditioner, or a cleanser would support the improvement of dry skin by constituting 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 and/or the use of known technique to improve similar devices (methods, or products) in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant under KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments with respect to claims 1, 5, 7-10, 15-17, 27, and 32-36 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. However, the Examiner would like to address Applicants’ arguments as they pertain to the new rejection supra.
It is acknowledged that the substitution of Ile to Val at the position corresponding to instant X3 was not previously addressed. However, given that not every encompassed embodiment recited in instant claim 1 is required to be rejected, it is unnecessary for the Examiner to reject each and every embodiment encompassed by a Markush group. Furthermore, as discussed in the new rejection supra, Golembo et al. does teach a specific CNP analog sequence with the substitution at the position corresponding to instant X3 from Ile to Val where this substitution is located at a cleavage site thereby suggesting that such a substitution would reduce protein degradation. Therefore, contrary to Applicant’s argument, Golembo does contemplate a CNP analog sequence with a substitution of Ile to Val at the position corresponding to instant X3.
Accordingly, the rejections of claims 1, 5, 7-10, 15-17, 27, and 32-36 are maintained as Applicants’ arguments are found unpersuasive.
Conclusion
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
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