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 .
DETAILED ACTION
Application status
Claims 150-179 are pending in this application.
Priority
It is acknowledged that the instant application is a CON of PCT/US2021/034576 filed on 05/27/2021, which claims benefit of 63030870 filed on 05/27/2020.
Election
Applicant's election of Group II, Claims 166-179 in the response filed on 08/12/2025, 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 § 818.03(a)).
Applicants’ election of species: ENPP1-Fc polypeptide (agent), subject having a tissue injury (treatment), and saline (carrier), is acknowledged. Applicants traverse the election of species saline, noting that election of saline is not relevant to the elected Group II, which is drawn to a methods of treatment.
Applicants’ argument is found persuasive and the species election requirement for carrier is withdrawn.
Claims 150-165 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention.
For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/09/2023, 08/17/2023, 05/20/2024, and 06/18/2024 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 166 is objected to because of the following informalities:
Claim 166 is objected to because the recitations of abbreviations “ENPP1” and “ENPP3” without writing out in full what these terms abbreviate. The Examiner suggest replacing the noted terms with ---ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1)--- and ---ectonucleotide pyrophosphatase/phosphodiesterase-3 (ENPP3)---, respectively
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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.
Claims 166-179 are rejected under 35 U.S.C. § 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 166-172 and 174-179 recite “ENPP3 agent” which is unclear because it is not defined in the specification like the “ENPP1 agent”. On page 26 of the instant specification, the phrase “ENPP1 agent” is defined as:
“the term "ENPP1 agent" refers to ENPP 1 polypeptide or fusion protein or ENPP 1 fragment comprising at least catalytic domain capable of producing plasma pyrophosphate (Ppi) by cleavage of adenosine triphosphate (ATP) or a polynucleotide such as cDNA or RNA encoding ENPP 1 polypeptide or fusion protein or ENPP 1 fragment comprising at least catalytic domain capable of producing PPi by enzymatic cleavage of ATP or a vector such as a viral vector containing a polynucleotide encoding the same.”
However, such definition does not exist for “ENPP3 agent” rendering what the phrase encompasses unclear. In the interest in advancing prosecution, the phrase “ENPP3 agent” is interpreted as similarly as “ENPP1 agent, referring to “ENPP3 polypeptide or fusion protein or ENPP3 fragment comprising at least catalytic domain capable of producing plasma pyrophosphate (Ppi) by cleavage of adenosine triphosphate (ATP) or a polynucleotide such as cDNA or RNA encoding ENPP3 polypeptide or fusion protein or ENPP3 fragment comprising at least catalytic domain capable of producing PPi by enzymatic cleavage of ATP or a vector such as a viral vector containing a polynucleotide encoding the same.”
Claim 166 (167-179 dependent therefrom) recites the phrase “administering…to reduce and/or prevent progression of vascular smooth muscle cell proliferation” which is a term of degree rendering this claim unclear. It is unclear what is considered reduction or prevention in comparison to. The Examiner suggests inserting a phrase “compared to untreated subject” or the like.
Claim 177 recites the phrase “the heterologous protein increases the circulating half-life” which is a term of degree rendering this claim unclear. It is unclear what is considered an increase in comparison to. The Examiner suggests inserting a phrase “compared to untreated subject” or the like.
Claim 179 recites the limitation “the ENPP1 or ENPP3 peptide” in claim 177. There is insufficient antecedent basis for this limitation in the claim. The Examiner suggests replacing the noted phrase with ---the ENPP1 or ENPP3 polypeptide---.
The following is a quotation 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.
Claims 166-174 and 176-179 are rejected under 35 U.S.C. § 112(a), written description, 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(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of a genus of any ENPP1 or ENPP3 agent, including any ENPP1 or ENPP3 variants that retain enzymatic activity, effective to reduce and/or prevent progression of vascular smooth muscle cell proliferation at the site of injury or the surgical site in the subject (italicized for added emphasis, the scope of claim 166 is given a broadest, reasonable interpretation based on claim 172).
To satisfy the written description aspect of 35 U.S.C. § 112(a) for a claimed genus of [compositions or methods], it must be clear that: (1) the identifying characteristics of the claimed [compositions or methods] have been disclosed, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these; and (2) a representative number of species within the genus must be disclosed.
University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lily and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description as noted from Enzo Biochemical (see above).
The specification discloses only a single representative species of ENPP1 or ENPP3 variants thereof, i.e., amino acids 99 to 925 SEQ ID NO: 1 fused to Fc, that can be used in the claimed method. However, this single disclosed species fails to provide adequate written description for a genus of any ENPP1 or ENPP3 variants that retain enzymatic activity. The instant specification fails to describe any identification of structural characteristics or properties of any ENPP1 or ENPP3 variants as to which amino acids can be modified, including any addition, deletion, substitutions, and/or covalent modifications, in order to retain the desired enzymatic activity. As such, the genus of “any ENPP1 or ENPP3 variants that retain enzymatic activity” encompasses widely variant species, having essentially any structure.
It is noted by the Examiner that all of the dependent claims, with the exception of claim 175, fail to remedy the deficiency noted above regarding the written description requirement.
While M.P.E.P. section 2163 acknowledges that a single species can describe a genus, it also acknowledges that for a genus that encompasses widely variant species, disclosure of a single species within the genus fails to adequately describe all members of the genus. Please refer to the M.P.E.P. section 2163.05 [R-7.2022] under I, B for more details with respect to sufficient number of representative species that should be disclosed to describe a widely variant genus.
Given the lack of additional representative species of a genus of any ENPP1 or ENPP3 variants that retain enzymatic activity, which can be used in the claimed methods, as encompassed, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112(a) published in the Official Gazette and also available at www.uspto.gov.
Claims 166-179 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of an ENPP1 polypeptide; a nucleic acid encoding an ENPP1; or a viral vector comprising a nucleic acid encoding an ENPP1 polypeptide, effective to reduce and/or prevent progression of vascular smooth muscle cell proliferation at the site of injury or the surgical site in the subject, does not reasonably provide enablement for a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of an ENPP3 polypeptide; a nucleic acid encoding an ENPP3; or a viral vector comprising a nucleic acid encoding an ENPP3 polypeptide, effective to reduce and/or prevent progression of vascular smooth muscle cell proliferation at the site of injury or the surgical site in the subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breath of the claims. The factors which have lead the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breath of the claims. Claims are drawn to a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of an ENPP1 or ENPP3 agent effective to reduce and/or prevent progression of vascular smooth muscle cell proliferation at the site of injury or the surgical site in the subject.
In addition, claims encompass methods of using a stent coated with nucleic acids and/or mRNA, encoding EPP1 or EPP3 proteins (especially see claims 173 and 176).
The amount of direction or guidance presented and the existence of working examples. The specification is limited in the disclosure of a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of an ENPP1 polypeptide or ENPP1-Fc fusion polypeptide as shown in Figures 1-9 and Examples on pages 152-169. However, the specification is prophetic with regard to the use of ENPP3 agent, and there is no actual data shown which is obtained from using the ENNP3 agent.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art.
Based on the reference of Zhou et al. (GRIA2/ENPP3 Regulates the Proliferation and Migration of Vascular Smooth Muscle Cells in the Restenosis Process Post-PTA in Lower Extremity Arteries, Front. Physiol., Vol. 12, Article 712400, published on 08/24/2021), Zhou et al. teach that there is a key evidence for ENPP3’s significant upregulation in restenotic plaques post-angioplasty, which mediates promotion of vascular smooth muscle cells (VSMC) proliferation and migration (see Abstract and Figures 4 and 5 on pages 8-9; and see page 5, right column, last para continued to page 6, left column).
Furthermore, regarding the use of a stent coated with nucleic acids and/or mRNA, encoding EPP1 or EPP3 proteins (especially see claims 173 and 176), the state of prior art recognizes that nucleic acids and mRNAs cannot be encoded out in a blood stream where the stent is placed without any transcription and/or translation machinery required for protein synthesis. This becomes an issue since it is the encoded ENPP1 proteins which provide the desired therapeutic effect of reducing or preventing progression of vascular smooth muscle cells.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While a method of administering ENPP1-Fc fusion protein which prevented mortality, vascular calcification, and sequela of disease in animal models of generalized arterial calcification of infancy was well-known in the relevant field of art, prior to the effective filing date of the instant application, see Albright et al. (ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy, Nature Communications, volume 6, Article number: 10006 published on 12/01/2015, see IDS), the relevant field of art at the time of invention does not show that [i] an ENPP3 agent, or [ii] a stent coated with nucleic acids and/or mRNA encoding ENPP1 without the required transcription/translation machinery in blood can be used in a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site. The reference of Zhou et al. as discussed above clearly demonstrates that such method would not work as intended due to ENPP3 promoting vascular smooth muscle cells (VSMC) proliferation and migration in such patients.
For the reasons discussed above, the invention as claimed does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Claim Rejections - 35 U.S.C. § 102
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 166, 168 and 172-179 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Khan et al. (ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy, Dis Model Mech (2018) 11 (10), pages 1-10) in view of the evidentiary reference of Albright et al. (ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy, Nature Communications, volume 6, Article number: 10006 published on 12/01/2015, see IDS).
The instant claims are drawn to a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of an ENPP1 or ENPP3 agent effective to reduce and/or prevent progression of vascular smooth muscle cell proliferation at the site of injury or the surgical site in the subject.
Khan et al. teach a method of administering to the subject (in this case Enpp1asj-2J homozygous mice (Asj-2J or Asj-2J hom), a model previously described to show extensive mineralization in the arterial vasculature, similar to generalized arterial calcification of infancy (GACI) patients) an amount of a recombinant human ENPP1 (rhENPP1) in a disease prevention study, such administration showed >95% reduction in aorta calcification, thereby reducing progression of vascular smooth muscle cell proliferation at the site of injury in the subject (see abstract), which anticipates claim 166.
Claim 168 is included in this rejection because said mice have extensive mineralization in the arterial vasculature which is inclusive of tissue injury comprising an injury to an artery.
Claims 172-179 are included in this rejection because said rhENPP1 is made in accordance with the evidentiary reference of Albright et al. (ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy, Nature Communications, volume 6, Article number: 10006 published on 12/01/2015, see IDS) which comprises the soluble portion of human ENPP1 (NCBI accession NP_006199), identical to Applicants’ amino acids 99 to 925 of SEQ ID NO: 1, fused to the human IgG1 Fc domain at the C-terminus, wherein said human ENPP1 (see below sequence alignment of Sbjct: NCBI accession NP_006199 with Query: Applicants’ SEQ ID NO: 1; and page 3, Figure 2 b of Albright et al.)
Therefore, the reference of Khan et al. anticipates the Applicants’ claimed methods.
ectonucleotide pyrophosphatase/phosphodiesterase family member 1 [Homo sapiens]
Sequence ID: NP_006199.2Length: 925Number of Matches: 1
Related Information
Gene-associated gene details
AlphaFold Structure-3D structure displays
Genome Data Viewer-aligned genomic context
Range 1: 1 to 925GenPeptGraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score
Expect
Method
Identities
Positives
Gaps
1931 bits(5002)
0.0
Compositional matrix adjust.
925/925(100%)
925/925(100%)
0/925(0%)
Query 1 MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPL 60
MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPL
Sbjct 1 MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPL 60
Query 61 EKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNC 120
EKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNC
Sbjct 61 EKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNC 120
Query 121 RCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINY 180
RCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINY
Sbjct 121 RCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINY 180
Query 181 SSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKK 240
SSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKK
Sbjct 181 SSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKK 240
Query 241 CGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEW 300
CGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEW
Sbjct 241 CGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEW 300
Query 301 YKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLP 360
YKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLP
Sbjct 301 YKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLP 360
Query 361 KDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLIL 420
KDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLIL
Sbjct 361 KDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLIL 420
Query 421 ISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSC 480
ISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSC
Sbjct 421 ISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSC 480
Query 481 REPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNV 540
REPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNV
Sbjct 481 REPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNV 540
Query 541 FSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVY 600
FSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVY
Sbjct 541 FSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVY 600
Query 601 TPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYG 660
TPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYG
Sbjct 601 TPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYG 660
Query 661 RPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPL 720
RPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPL
Sbjct 661 RPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPL 720
Query 721 SPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTL 780
SPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTL
Sbjct 721 SPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTL 780
Query 781 LRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKD 840
LRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKD
Sbjct 781 LRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKD 840
Query 841 TSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSF 900
TSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSF
Sbjct 841 TSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSF 900
Query 901 YQQRKEPVSDILKLKTHLPTFSQED 925
YQQRKEPVSDILKLKTHLPTFSQED
Sbjct 901 YQQRKEPVSDILKLKTHLPTFSQED 925
Claim Rejections - 35 U.S.C. § 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.
Claim 166-179 are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al. (ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy, Dis Model Mech (2018) 11 (10), pages 1-10) in view of Ziegler et al. (Generalized Arterial Calcification of Infancy, Gene Reviews, 2014 Nov 13), and the evidentiary reference of Albright et al. (ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy, Nature Communications, volume 6, Article number: 10006 published on 12/01/2015, see IDS).
The instant claims are drawn to a method for reducing and/or preventing progression of vascular smooth muscle cell proliferation in a subject having a tissue injury or a subject who has a condition requiring surgery at a surgical site, said method comprising: administering to the subject an amount of an ENPP1 or ENPP3 agent effective to reduce and/or prevent progression of vascular smooth muscle cell proliferation at the site of injury or the surgical site in the subject.
Teachings of Khan et al. are as described above.
Ziegler et al. teach that patients with GACI exhibit severe coronary, arterial stenosis, myocardial infarction (see page 11 under “Treatment of Manifestations”, hypertension and severe coronary stenosis; page 7 under “Prognosis”), which reads on claims 167 and 171.
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the claimed invention to practice the methods taught by Khan et al. especially for patients who are at risk of developing arterial stenosis or myocardial infarction as taught by Ziegler et al. Likewise, it would have been obvious for a POSITA to practice such methods for [i] patients who are at risk of developing restenosis (means re-narrowing of an artery) due to stent placement (claim 169), or for [ii] patients who require a surgery for angioplasty (claim 170). One would have been motivated to practice such methods because administrating a recombinant human ENPP1 (rhENPP1) showed >95% reduction in aorta calcification, thereby reducing progression of vascular smooth muscle cell proliferation at the site of injury in the subject (see teachings of Khan et al. above), which would be beneficial for patients with arterial stenosis, restenosis after stent placement, or those who require angioplasty, all due to narrowing or re-narrowing of an artery. One would have had a reasonable expectation of success to practice such methods because all of the required biochemical materials, and medical techniques were rampantly available as evidenced by Khan et al., Ziegler et al., and Albright et al. prior to the filing of the instant application. Therefore, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Conclusion
Claims 166-179 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656