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 .
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 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.
Priority
The instant application, filed 04/13/2023, is a 371 filing of PCT/US21/55028, filed 10/14/2021, and claims domestic benefit to US provisional application 63/091,558, filed 10/14/2020.
Status of Claims/Application
The preliminary amendment of 04/13/2023 is acknowledged. Claims 4 and 12-15 are amended; and claims 18-20 are new. Claims 1-20 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/08/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
The sequence listing incorporation by reference paragraph in the specification provides the sequence listing size in kilobytes (KB) rather than the required byes. See items 1) a) iii) and 1) b) iii) below.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The drawings are objected to because the resolution of the figures are low and are difficult to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 2-3 and 11 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.
Claims 2 and 11 recite the limitation “endocarditis (bacterial, viral, or fungal)”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 2 and 11 recite the broad recitation endocarditis, and the claim also recites “bacterial, viral, or fungal” in parentheticals, which is the narrower statement of the preceding limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. This is particularly the case as endocarditis does not necessarily have to be bacterial, viral, or fungal.
Appropriate correction is required.
Claim 3 is rejected by virtue of its dependency on claim 2 as it does not resolve the ambiguity discussed above.
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-9 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over US 2003/0219898 A1 (Sugaya, K., et al) 27 Nov. 2003.
US’898 teaches methods of treating neurological or corporal deficits without the problems associated with heterologous transplants from adult or fetal sources (page 8, [0075]). US’898 teaches that corporal deficits are a target for amelioration and refers to a disorder caused by a wide variety of diseases including trauma, malfunction, degeneration or loss of muscle such as, for example, cardiac muscle due to myocardial infarction (page 3, [0022]; page 16, [0152]-[0153]). US’898 teaches that injuries that can be treated according to the methods disclosed include ischemia and injuries caused by a stroke, including a global stroke, as may be caused by cardiac arrest, arrhythmia, or myocardial infarction (page 15, [0140]).
US’898 teaches methods of altering the migration and/or differentiation of endogenous or exogenous multipotent stem cells in a mammal by modulating the levels of APP and/or reelin in the mammal. US’898 teaches an embodiment in which the amount of reelin in a mammal is altered by administration of reelin protein (page 5, [0035]).
US’898 teaches that reelin is a large extracellular matrix protein of approximately 400 kDa and that it has been found that reelin plays an important role in regulation of NSC biology. The addition of recombinant reelin to NSCs in culture increased mobility of cells in the cluster of cells that typified their growth. When NSCs were transplanted in the brain of reeler homozygous mice that do not express reelin, migration was nearly halted. It was found that only cells expressing reelin migrated into the cortex of reeler homozygous mice. These results suggest that reelin is an indispensable factor for the migration of NSCs or more developmentally potent cells (pages 16-17, [0158])-[0159]).
Mammals with suppressed reelin expression may not experience proper migration of endogenous or exogenous multipotent cells. The reelin protein can be administered to a mammal in need. For example, reelin can be introduced at the site of a stroke to encourage the migration of multipotent cells into the area of damage to start repair (page 17, [0160]).
While US’898 does not exemplify the administration of the reelin peptide to treat the disclosed diseases or conditions of the heart, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to administer the reelin peptide to treat the diseases or conditions of the heart as US’898 teaches administration of reelin for such diseases or conditions. Thus, an ordinarily skilled artisan would have had a reasonable expectation of success.
Regarding claims 4-5, while US’898 does not experimentally demonstrate the claimed outcomes, such outcomes would have been expected in view of the teachings of US’898. As discussed above US’898 teaches the amelioration of corporal defects, including ischemia, stroke, cardiac arrest, arrhythmia, or myocardial infarction. As US’898 teaches that these defects are treated with reelin, an ordinarily skilled artisan would reasonably expect that the defects/conditions disclosed would be alleviated sooner than untreated controls.
Additionally, the outcomes recited would flow naturally from following the teachings of US’898 in which reelin is administered to patients with the disclosed conditions.
MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Claims 1-12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over US 9,486,484 B2 (Alfonso, Z. and J.K. Fraser) 8 Nov 2016 in view of Lutter, S., et al (2012) Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation J. Cell. Biol. 197(6); 837-849 and US 2003/0219898 A1 (Sugaya, K., et al) 27 Nov. 2003.
US’484 teaches methods of treating a disease or disorder selected from a group that includes cardiovascular disease and heart disease comprising administering an isolated population of adipose derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs (col. 12, lines 18-36). US’484 further teaches that the importance of molecules including hyaluronan, integrins, reelin, IL-7, and matrix metalloproteinases in LEC growth, migration, tube formation, and survival have been reported. In some embodiments, one or more of these molecules is used to enhance or modify the activity of the cells by co-administration (page 62, lines 48-61).
US’484 teaches that the lymphatic system plays a dual role in fluid transport and immune surveillance. In fluid transport, extravasated fluid and macromolecules pass into lymphatic vessels that are lined by a single layer of lymphatic endothelial cells (LECs) surrounded by an incomplete basement membrane. Fluid is transferred from these vessels into larger vessels, many of which are lined by lymphatic smooth muscles that exhibit spontaneous beating, which, in concert with the action of adjacent skeletal muscle, pumps the lymph fluid back to the venous system through the thoracic duct (col. 1, lines 39-50).
A number of pathological conditions exist in which the ability of the lymphatic system to transport fluid is insufficient to meet demand. This leads to tissue edema that is disfiguring, disabling, and, on occasion, life threatening. There are, thus, a number of settings in which modulation of expansion or repair of the lymphatic system are clinically desirable. Acute myocardial infarction leads to increased vascular permeability, thereby increasing the amount of fluid and macromolecules in the interstitial space for removal by the lymphatic system. This edema leads to tissue injury throughout the ventricle, causing histologically visible gaps between vascular endothelial cells and activation of platelets that reduce blood vessel patency. Myocardial edema is evident in many clinical states and can be caused or worsened by cardiac surgery and myocardial infarction. The consequences of edema have been studied in animal models of chronic lymphatic obstruction. These studies indicate myofibrillar disruption resulting from edema-induced separation of cardiac monocytes and formation of non-elastic scar tissue which can, in turn, lead to impaired conductance and arrythmia (col. 2, lines 23-48).
US’484 further teaches that myocardial edema can result in comprised cardiac function. Causes of myocardial edema include cardiac surgery, as well as myocardial ischemia, arterial or pulmonary hypertension, and cardiac transplant. The methods taught can be used to increase lymphatic function either directly, e.g. through cell engraftment, or indirectly, e.g., by secreting factors that stimulate growth or activity of the existing lymphatic system. Secreted factors can act on host cells and/or cells administered according to the methods disclosed (col. 70, lines 21-27).
US’484 teaches that treatment includes reducing or alleviating at least one adverse effect or symptom of a lymphatic system condition, disease, or disorder, i.e., any disorder characterized by abnormal, anomalous, or insufficient lymphatic function (col. 19, lines 19-26).
US’484 further teaches compositions that include collagen matrix or support (col. 61, lines 26-27, and teaches that the composition can be for surgical implantation at a particular site (col. 61, lines 64-65).
The selection and use of reelin in the methods taught by US’484 is further supported by the prior art. US’484 also does not explicitly teach that the reelin is a reelin polypeptide or a variant thereof.
Lutter teaches that active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels. Lutter identifies reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as a an important regulator of lymphatic vascular development (abstract). Reelin is identified as a lymphatic-specific matrix molecule and demonstrates its important function in the formation of functional collecting lymphatic vessels. In addition, Lutter teaches a unique mechanism by which reelin signaling is activated via communication between the two cell types that form the collecting vessels: endothelial and smooth muscle cells (SMCs). The specific defects displayed by Reln-deficient mice further highlight a hitherto unrecognized important function of SMCs in lymphatic vessel morphogenesis and function (page 838, left column, paragraph 2).
Lutter also analyzed reelin expression and secretion by lymphatic ECs (LECs ) cultured alone or together with SMCs and teaches that LECs produce reelin protein (paragraph bridging pages 840-841). Lutter further teaches that reelin acts in an autocrine fashion in LECs to induce production of SMC recruitment factors and teaches a transient increase in regulators of SMC recruitment and migration in LECs upon reelin stimulation (page 844, left column, paragraph 1).
The teachings of US’898 are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to select reelin for use in the methods disclosed by US’484 based on the teachings of US’484, Lutter, and US’898. It would have further been obvious to administer a reelin polypeptide, including a recombinant reelin polypeptide, based on the teachings of US’898. An ordinarily skilled artisan would have been motivated to select reelin for use in the methods of US’484 as US’484 teaches that the importance of reelin has been identified in LEC growth, migration, tube formation, an survival. The selection of reelin is further motivated by Lutter which demonstrates that reelin is important in regulating the formation of functional lymphatic vessels and is involved in a signaling pathway between LECs and SMCs. US’898 also motivates the use of reelin in the methods of US’484 as US’898 teaches that reelin protein can be administered to heart related conditions to encourage migration of multipotent cells into the area of damage to start repair. An ordinarily skilled artisan would have had a reasonable expectation of success as US’484 teaches the use of reelin in the methods disclosed. Additionally, both US’484 and Lutter teach the importance of reelin in the formation of lymphatic vessels and both US’484 and US’898 teach methods of treating diseases or conditions of the heart using reelin. It would have further been obvious to administer a reelin polypeptide, including a recombinant reelin polypeptide, as the administration of a reelin protein is taught by US’898 as a means to treat heart related conditions. Thus, an ordinarily skilled artisan would have had a reasonable expectation of success.
Regarding claims 4-5, and 9, while the combination of US’484, Lutter, and US’898 do not experimentally demonstrate the claimed outcomes, such outcomes would have been expected in view of the teachings of the combination of applied references. For instance, as discussed in detail above US’484 teaches methods for the improvement of cardiac lymphatics and a reduction in fluid accumulation following cardiac conditions, including myocardial infarction, by administration of reelin. US’898 teaches the amelioration of corporal defects, including ischemia, stroke, cardiac arrest, arrhythmia, or myocardial infarction. As the combination of US’484, Lutter, and US’898 teach that the disclosed defects/conditions are treated with reelin, an ordinarily skilled artisan would reasonably expect that the defects/conditions disclosed would be alleviated sooner than untreated controls and would be a measurable improvement.
Additionally, the outcomes recited would flow naturally from following the teachings of the combination of US’484, Lutter, and US’898 in which reelin is administered to patients with the disclosed conditions.
MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over US 9,486,484 B2 (Alfonso, Z. and J.K. Fraser) 8 Nov 2016 in view of Lutter, S., et al (2012) Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation J. Cell. Biol. 197(6); 837-849 and US 2003/0219898 A1 (Sugaya, K., et al) 27 Nov. 2003 as applied to claim 1 above, and in further view of WO 2011/091304 A1 (Watts, R.J., et al) 28 July 2011.
The combination of US’484, Lutter, and US’898 teach the method of claim 1 as discussed in detail above.
The combination of applied references, however, do not expressly disclose that the reelin polypeptide comprises SEQ ID NO: 1 or a fragment thereof.
WO’304 teaches that the amino acid sequence of naturally occurring human reelin is presented in SEQ ID NO: 3, from Genbank AAC51105.1 (page 16, line 14 – page 18, line 13). WO’304 teaches administration of reelin as a shuttle agent that binds to LRP8 and also teaches that fragments of human reelin can be used that maintain binding to the receptor (page 81, claim 5).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to use the human reelin polypeptide sequence disclosed by WO’304 in the method disclosed by the combination of US’484, Lutter, and US’898. It would have been obvious to an ordinarily skilled artisan to use polypeptide sequence disclosed by WO’304 as it is the art recognized sequence of human reelin which is the protein that is taught by the combination of US’484, Lutter, and US’898. Thus, an ordinarily skilled artisan would have had a reasonable expectation of success. The expectation of success is further supported by WO’304 which demonstrates that administration of reelin with the recited sequence had been considered in the art.
Claims 14 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over US 9,486,484 B2 (Alfonso, Z. and J.K. Fraser) 8 Nov 2016 in view of Lutter, S., et al (2012) Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation J. Cell. Biol. 197(6); 837-849 and US 2003/0219898 A1 (Sugaya, K., et al) 27 Nov. 2003 as applied to claim 1 above, and in further view of Serpooshan, V., et al (2013) The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction Biomaterials 34(36); 1-15.
The combination of US’484, Lutter, and US’898 teach the method of claim 1 as discussed in detail above.
As discussed above, US’484 teaches compositions that include collagen matrix or support (col. 61, lines 26-27), and teaches that the composition can be for surgical implantation at a particular site (col. 61, lines 64-65).
The combination of applied references, however, do not expressly disclose that the collagen matrix composition is in the form of a collagen patch.
Serpooshan teaches an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted onto the infarcted myocardium in adult murine hearts immediately after ligation of the left anterior descending artery and the physiological outcomes were monitored by echocardiography and by hemodynamic and histological analyses four weeks post infarction. In comparison to infracted hearts with no treatment, hearts bearing patches preserved contractility and significantly protected cardiac tissue from injury at the anatomical and functional levels. This improvement was accompanied by attenuated left ventricular remodeling, diminished fibrosis, and formation of a network of blood vessels within the infarct. Histological and immunostaining confirmed integration of the patch with native cardiac cells including fibroblasts, smooth muscle cells, epicardial cells, and immature cardiomyocytes. In summary, Serpooshan teaches an acellular biomaterial that promotes endogenous capacity of the infracted myocardium to attenuate remodeling and improve heart function following myocardial infarction (abstract). Serpooshan also considers further investigations on therapeutic factors and/or cells that can be seeded within the engineered patch for cardiac repair following severe heart injuries (pages 6-7, conclusion).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to substitute the collagen matrix taught by the combination of US’484, Lutter, and US’898 with the collagen patch disclosed by Serpooshan for delivery of the reelin polypeptide treatment. An ordinarily skilled artisan would have been motivated to use the patch of Serpooshan as Serpooshan teaches that the collagen patch is able to promote the endogenous capacity of the infracted myocardium and attenuate remodeling and improve heart function following heart injury, which would further contribute to the treatment methods disclosed by US’484, Lutter, and US’898. An ordinarily skilled artisan would have had a reasonable expectation of success because US’484, Lutter, and US’898 teach delivery of reelin via collagen matrix for the treatment of heart conditions, including myocardial infarction, which is the same type of matrix and injury disclosed by Serpooshan. Additionally, Serpooshan also considered the seeding of the patches with therapeutic factors and/or cells.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Serpooshan, V., et al (2013) The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction Biomaterials 34(36); 1-15 in view of US 9,486,484 B2 (Alfonso, Z. and J.K. Fraser) 8 Nov 2016, Lutter, S., et al (2012) Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation J. Cell. Biol. 197(6); 837-849, and US 2003/0219898 A1 (Sugaya, K., et al) 27 Nov. 2003.
The teachings of Serpooshan are as discussed above.
Serpooshan, however, does not disclose that the therapeutic factor seeded in the collagen patch is a reelin polypeptide.
The teachings of US’484, Lutter, and US’898 are as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the collagen patch of Serpooshan by seeding a reelin polypeptide in the collagen patch based on the teachings of US’484, Lutter, and US’898. An ordinarily skilled artisan would have been motivated to seed a reelin polypeptide in the collagen patch in order to promote expansion and tissue repair of the lymphatic system, which US’484 teaches is beneficial following cardiac events, such as myocardial infarction. The use of reelin is further supported by Lutter which demonstrates that reelin is important in regulating the formation of functional lymphatic vessels and is involved in a signaling pathway between LECs and SMCs. US’898 also motivates the inclusion of a reelin polypeptide teaching that reelin protein can be administered to heart related conditions to encourage migration of multipotent cells into the area of damage to start repair. An ordinarily skilled artisan would have had a reasonable expectation of success as Serpooshan teaches the use of collagen patches, which can be seeded with therapeutics, in the treatment and improvement of heart function following myocardial infarction, which is the same condition taught by both US’484 and US’898. Additionally, both US’484 and Lutter teach the importance of reelin in the formation of lymphatic vessels and both US’484 and US’898 teach methods of treating diseases or conditions of the heart using reelin. Additionally, US’484 teaches methods using a collagen matrix and Serpooshan teaches the seeding of therapeutics in such a matrix.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Serpooshan, V., et al (2013) The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction Biomaterials 34(36); 1-15 in view of US 9,486,484 B2 (Alfonso, Z. and J.K. Fraser) 8 Nov 2016, Lutter, S., et al (2012) Smooth muscle-endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation J. Cell. Biol. 197(6); 837-849, and US 2003/0219898 A1 (Sugaya, K., et al) 27 Nov. 2003 as applied to claim 16 above, and in further view of WO 2011/091304 A1 (Watts, R.J., et al) 28 July 2011.
The combination of Serpooshan, US’848, Lutter, and US’898 teach the composition of claim 16 as discussed in detail above.
The combination of applied references, however, does not disclose that the reelin polypeptide comprises instant SEQ ID NO: 1 or a fragment thereof.
The teachings of WO’304 are as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to use the human reelin polypeptide sequence disclosed by WO’304 in the composition disclosed by the combination of Serpooshan, US’848, Lutter, and US’898. It would have been obvious to an ordinarily skilled artisan to use polypeptide sequence disclosed by WO’304 as it is the art recognized sequence of human reelin which is the protein that is taught by the combination of Serpooshan, US’848, Lutter, and US’898. Thus, an ordinarily skilled artisan would have had a reasonable expectation of success. The expectation of success is further supported by WO’304 which demonstrates that administration of reelin with the recited sequence had been considered in the art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AUDREY L BUTTICE whose telephone number is (571)270-5049. The examiner can normally be reached M-Th 8:00-4:00.
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/AUDREY L BUTTICE/Examiner, Art Unit 1647
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693