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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a hydrogel conjugate of a CNP, claimed in claims 1-12 and 14 in the reply filed on 2/18/26 is acknowledged. Election was made of SEQ ID NO: 4, Formula IV (new claim 18) as the hydrogel and the linker variables (claim 5) are: Z is a triazole, n=1, R4 is CH3, R1 is N,N-dimethylamino)SO2 and R2 is H.
Claims 1-18 are pending
Claims 13 and 15-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group or species, there being no allowable generic or linking claim.
Claims 1-12, 14 and 17-18 are under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-12 and 14 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 1 is drawn to a hydrogel conjugate of a C-natriuretic peptide having formula I: M-(L-E)a, wherein M is a hydrogel matrix, L is a linker, E is a C-natriuretic peptide and a is an integer that represent the number of L-E moieties that yield a suitable concentration of E in a given volume of matrix.
The USPTO provides claim terms with broadest reasonable interpretation in light of the specification. The instant specification defines “CNP” [PGPUB0054]:
The term “CNP” includes all peptides characterized by the ability to bind NPR-B and thereby regulate the growth, proliferation, and differentiation of chondrocytes. This includes, without limitation, sequences listed in PCT Publications 2009/067639, 2010/135541, and 2016/110577; and Morozumi et al. (2019) PLoS ONE 14(2): e0212680. Preferably, the term “CNP” refers to a peptide of SEQ ID No: 1-6 and stabilized analogs thereof. Particularly preferred are CNP analogs wherein particular amino acid residues have been replaced so as to improve the stability of the peptide.
Therefore, the CNP is not limitation by size or structure and includes variants and mutants.
The instant specification states that the hydrogels are extended release [PGPUB0003], however the structure of the linker and hydrogel are broad.
Assessment of whether species are support in the original specification
Two embodiment of the invention of the claims were reduced to practice (claims 17 and 18). Furthermore, the instant specification discloses the structure of the CNP as SEQ ID NO: 1-6.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the disclosure of SEQ ID NOs: 1-6 are not representative of the genus of CNP that can include mutants and fragments thereof. Furthermore, the hydrogel and linker of claims 17 and 18 (also Fig. 3) are not representative of the broad genus of hydrogel of Formula III (claim 4) and linker of claim 5. Importantly, claim 1 recites that “a” is an integer representing the number of L-E moieties that yield a suitable concentration of E in a given volume of matrix, but the range of the integer is not defined in the claim. Consequently, the disclosure does not reasonable convey that one of ordinary skill in the art had full possession of the full scope of hydrogel-CNP conjugates.
Identifying characteristics and structure/function correlation
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. In the instant case, the claims encompass a broad species of peptide, linker and hydrogel and the specification only provides limited working examples involving a specific hydrogel, specific linker and specific CNP peptide. The specification states that the hydrogel have extended release properties but provides the support for only specific hydrogel. The disclosure does not demonstrate that hydrogels with different linkers and hydrogel structure or different values of “a” would necessarily exhibit extended release properties.
Satish et al. (Indian Journal of Pharmaceutical Sciences, April 2006) states that factors like polymer composition, water content, crosslinking density and crystallinity ca be used to control the release rates and release mechanisms from hydrogels (p. 133, bottom of 1st col.). Therefore, the art recognizes that the release behavior in hydrogel conjugates is highly dependent on formulation parameters. Because the specification provides only limited working examples, the disclosure does not reasonably convey passion of the full scope of the claims.
The specification lacks representative species across the breadth of the claimed genus and does not identify structural common features that would lead to one of ordinary skill to recognize that the inventors had possession of the full scope of the claims.
Claim Rejections - 35 USC § 112
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.
Claims 1-12, 14 and 17-18 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.
Claim 1 is indefinite because the limitation “a is an integer that represent the number of L-E moieties that yield a suitable concentration of E in a given volume of matrix” is unclear. The claims fails to define what constitutes “a suitable concentration” of E. Therefore, the term “a suitable concentration” is a relative term which renders the claim indefinite. The limitation is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The value of “a” is determined by reference to the undefined and subjective term “suitable concentration”, therefore the claim scope is unclear.
Claims 2-12, 14 and 17-18 do not cure the deficiencies of claim 1 and rejected.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sprogoe et al. (WO2017/118700).
Please note that the instant specification defines “CNP” [PGPUB0054]:
The term “CNP” includes all peptides characterized by the ability to bind NPR-B and thereby regulate the growth, proliferation, and differentiation of chondrocytes. This includes, without limitation, sequences listed in PCT Publications 2009/067639, 2010/135541, and 2016/110577; and Morozumi et al. (2019) PLoS ONE 14(2): e0212680. Preferably, the term “CNP” refers to a peptide of SEQ ID No: 1-6 and stabilized analogs thereof. Particularly preferred are CNP analogs wherein particular amino acid residues have been replaced so as to improve the stability of the peptide.
Sprogoe et al. teach and claim a controlled release CNP agonist (claims 1 and 10). Sprogoe et al. defines “CNP agonist” : “As used herein the term "CNP agonist" refers to any compound that activates natriuretic peptide receptor B (NPR-B) and has an EC50 that is at most 50-fold higher than the NPR-B activity of CNP-22 (SEQ ID NO: l)” (middle of p. 3). Therefore, the CNP agonist of Sprogoe et al. meets the limitation of CNP of the instant claims. Sprogoe teach:
PNG
media_image1.png
66
226
media_image1.png
Greyscale
wherein D is a CNP agonist, L1 is a linker and L2 is a single chemical bond and Z is a water soluble carrier moiety (claim 10). Because the claim broadly recites a linker between the hydrogel and CNP and does not require the linker to consist of a specific structure, the linker and spacer region disclosed in Sprogoe satisfies the claimed linker region.
Therefore, Sprogoe et al. anticipates instant claim 1.
With respect to claim 2, Sprogoe et al. teach the sequence of CNP is SEQ ID NO: 24 which is identical to instantly claimed SEQ ID NO: 3 (p. 6).
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Sprogoe et al.
The teachings of Sprogoe et al. are presented in detail above. The reference does not teach the composition has a pH between 3 and 7, however the reference is suggestive of the limitation.
Sprogoe et al. teach the composition comprises buffering agents: physiologically tolerated buffers to maintain pH in a desired range. Sprogoe et al. teach physiological conditions refers to an aqueous buffer at pH 7.4.
It would have been obvious to a person of ordinary skill in the art to optimize the pH of the composition to arrive at the range of claim 1. The pH of a composition is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the pH, to arrive at the dose ranges of claim 14.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
Prosecution Insights