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 .
Claim Status
Claims 1, 3-4, and 29-45 are currently pending in this application and have been considered on the merits. All arguments have been fully considered.
Disclosure Objections (maintained)
The disclosure is objected to because of the following informalities: at each instance that “n1-(X1X2GXP)-n2” is followed by the denotation “(SEQ ID NO:8)” as a sequence identifier is improper because instant SEQ ID NO: 8 represents one or more repeats of a five amino acid residue sequence “(X1X2GX3P)n” where n is an integer ≥ 1 and X1, X2, and X3 are any naturally occurring amino acid residue while “n1-(X1X2GXP)-n2” means something completely different that is not properly represented by the scope of SEQ ID NO: 8. The sequence limitations of the “n1-“ and “-n2” notations, if any, are not clear and thus encompass a single amino acid, e.g., methionine, a polypeptide domain, e.g., an elastin domain, as well as an entire protein of over 2000 residues, e.g., fibrillin. Thus, “n1-“ and “-n2” encompass sequences fused to SEQ ID NO:8 lacking any G and/or P residues as well as sequences less than or more than five amino acid residues in length. This occurs at least in the abstract and paragraphs [0010], [0012]-[0018], and [0061] of the substitute specification. Appropriate correction is required. This would be remedied by rewriting “n1-(X1X2GXP)-n2” as “(X1X2GXP)n” or “(X1X2GXP)n1” or “(X1X2GXP)n2” and noting that n can be any whole number.
Response to Arguments
Applicant’s arguments of July 16, 2025 (pg. 7) are fully considered but not found to be persuasive. As set explained above, while SEQ ID NO: 8 is a proper identified for X1X2GXP, (X1X2GXP)n or (X1X2GXP)n, it is not a proper sequence identifier for “n1-(X1X2GXP)-n2”.
Claim Objections (new)
Claim 1 recites the phrase “wherein n is equal to or greater than 1 and a whole numbers,” which is grammatically unclear for stating n is a whole numbers mixing a singular article ‘a’ with a plural “numbers”. This would be clearer if rewritten as “wherein n is equal to or greater than 1 and a whole number” or alternatively “wherein n is a whole number equal to or greater than 1.” Appropriate correction is required.
Claim 42 recites “wherein the polypeptides consist of [(X1X2GXP)(X3X4GXP)]n1 (SEQ ID NO:71), [(X1X2GXP)n1(X3X4GXP)n2] (SEQ ID NO:72),” which be more grammatically correct if rewritten with a conjunction between “[(X1X2GXP)(X3X4GXP)]n1 (SEQ ID NO:71)” and “[(X1X2GXP)n1(X3X4GXP)n2] (SEQ ID NO:72),” such as “and” or “or”. Appropriate correction is required.
Previous Rejections
Status of the rejections:
The previous claim rejections under 112(b) are withdrawn in view of applicant’s amendments.
The previous claim rejections under 112(d) are withdrawn in view of applicant’s amendments except as maintained below.
The previous claim rejection under 102 is withdrawn in view of applicant’s amendments.
Claim Interpretation
In claim 1, for purposes of applying prior art the intended use language in the preamble “a three dimensional (3D) cell culture system” is considered but does not imply any additional structural limitation to the claimed product other than those positively recited in the claim beyond a biocompatibility with at least one type of cell culture. See MPEP 2111.02. In claim 1, the phrase “wherein the polypeptides differentiate the at least one of: induced pluripotent stem cells (iPSCs), or embryonic stem cells (ESCs) into cardiomyocytes” is considered but determined not to be limiting because the phrase does not imply any additional structural limitation to the claimed product other than those positively recited, and further the claimed product does not require any process step, such as a step of growing/culturing iPSCs or ESCs in or on the 3D culture system or the passage of time allowing for cell differentiating (see MPEP 2111.02). Thus, the phrase “wherein the polypeptides differentiate the at least one of: induced pluripotent stem cells (iPSCs), or embryonic stem cells (ESCs) into cardiomyocytes” is interpreted to require the three dimensional (3D) cell culture system be capable of the intended use of differentiating iPSCs or ESCs into cardiomyocytes and this functionality is inherent to the structure of the 3D cell culture system as positively recited in claim 1.
In claim 1, the term “fusion” with regard to protein is considered not to be a limitation as a given protein or 3D cell culture system comprising said protein does not necessarily reveal the manner in which the protein was obtained or made, such e.g., regard a process comprising fusing of polypeptides or amino acids. Furthermore, even if the claim was interpreted as a product-by-process claim, the patentability of a product-by-process claims relies solely on the claim limitations of the claimed product, either expressly recited or implied, regardless of the process, i.e., a fusing step implying no additional structure to the protein.
In claims 34-40 and 42, the phrase “the polypeptides consist of” regarding multiple sequence identifiers is interpreted as encompassing any polypeptides consisting of the sequences set forth by the recited SEQ ID NOs in any order directly fused together but with no additional sequences, e.g., SEQ ID NO:1+4 or SEQ ID NO:4+1 (claim 34); SEQ ID NO:1+2+3+4+5+68+69 (claim 40); or SEQ ID NO:71+72 or SEQ ID NO:72+71 (claim 42). Moreover in claim 40, the phrase “wherein the polypeptide has the sequence selected from at least one of [(X1X2GXP)(X3X4GXP)]n1 (SEQ ID NO:68), and [(X1X2GXP)n1(X3X4GXP)n2] (SEQ ID NO:69)” is interpreted as meaning the polypeptides each comprise at least one of SEQ ID NO: 68 and 69 as oppose to consists of at least one of SEQ ID NO: 68 and 69 so as to accommodate also comprising SEQ ID NOs. 1, 2, or 3.
In claim 45, the phrase “wherein the fusion protein consist of at least a portion of a growth factor or cytokine and an extracellular component” is interpreted to mean each fusion protein comprises both (1) a growth factor or cytokine, or a portion of either of the aforementioned, and (2) an extracellular matrix component or a portion thereof; such that a single fusion protein substructure (e.g., pentapeptide sequence or [SEQ ID NO:8]n) does not represent both a growth factor (or portion thereof) and an extracellular matrix component (or portion thereof), or both a cytokine (or portion thereof) and an extracellular matrix component (or portion thereof).
Claim Rejections - 35 USC § 112(b) (new)
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, 3-4, and 29-45 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 recites the phrase “when Tyrosine and Alanine are a mixture at position X they are at a 1:4 ratio of Tyrosine to Alanine,” which is ambiguous, incoherent or otherwise unclear as to what a mixture at a sequence position means. For example, “a mixture at position X” may refer to wherein n=1 and there are both a tyrosine and alanine residue at a single position X (in a 1:4 mixture) or wherein n ≥ 2 and the first X is tyrosine and the second X is alanine meaning a combination of Y and A throughout the polypeptide at a plurality of X positions requiring a minimum of five X positions total. Claims 3-4, and 29-45 are included in this rejection for being dependent on indefinite claim 1. For purposes of examination, the limitation “when Tyrosine and Alanine are a mixture at position X they are at a 1:4 ratio of Tyrosine to Alanine” is interpreted to mean if n=5 or greater and position X (X3) in some repeating SEQ ID NO: 8 unit is a tyrosine and in other repeating SEQ ID NO: 8 units is an alanine, then the ratio must be 1:4. This also requires n to be a whole number multiple of 5.
Each of claims 3 and 44-45 recites both the terms “the fusion protein” and “the polypeptide” with antecedent basis in claim 1 at “polypeptides or fusion proteins,” but which is ambiguous as to whether the two different terms are always or sometimes referring to the same or different molecules, which are clearly recited in the alternative in claim 1 in plural form.
In claims 3, 44 and 45, the fusion protein consists of at least a portion of an extracellular matrix component, growth factor and/or cytokine is ambiguous, incoherent or otherwise unclear as to whether the fusion protein may consist solely of an extracellular matrix component, growth factor or cytokine, or a portion thereof, comprising (SEQ ID NO: 8)n. It is unclear how the extracellular matrix component is “at an amino, a carboxy, or both the amino and carboxy ends of the polypeptides” in such a fusion protein as in claim 3 or wherein the fusion proteins are at an amino, a carboxy, or both the amino and carboxy ends of the polypeptides as in claims 44 and 45. Because these claims use the phrase “consists of,” there is a strong presumption this excludes all elements and components not specified in the claim as an extracellular matrix component, growth factor and/or cytokine, or at least a portion thereof (see MPEP 2111.03). Furthermore, there does not appear to be any growth factor, cytokine and/or extracellular matrix component consisting only of one or more repeats of SEQ ID NO: 8, and thus the fusion protein can only be a portion thereof.
Claim 30 recites the polypeptides of claim 1, which each consists of one or more repeats of SEQ ID NO: 8, also consist of one or more SEQ ID NO: 6; however this is incoherent as no combination of repeats of XXGXP (SEQ ID NO: 8) can also satisfy the sequence requirements of SEQ ID NO: 6 (YIGSRVGKKKKKKKKG).
Claim 31 recites the polypeptides of claim 1, which each consists of one or more repeats of SEQ ID NO: 8, also consist of one or more SEQ ID NO: 2; however this is incoherent as no combination of repeats of XXGXP (SEQ ID NO: 8) can also satisfy the sequence requirements of SEQ ID NO: 2 (RNAIA EIIKDI).
Claims 34-35 recites the polypeptides of claim 1, which each consists of one or more repeats of SEQ ID NO: 8, also comprise SEQ ID NO: 1; however this is incoherent as no species of SEQ ID NO: 8 (XXGXP)n can also satisfy the sequence requirements of SEQ ID NO: 1 (YIGSR).
Claims 36-37 recites the polypeptides of claim 1, which each consists of one or more repeats of SEQ ID NO: 8, also comprise SEQ ID NO: 3; however this is incoherent as no species SEQ ID NO: 8 can also satisfy the sequence requirements of SEQ ID NO: 3 (VGKKKKKKKKG).
Claims 38-39 recites the polypeptides of claim 1, which each consists of one or more repeats of SEQ ID NO: 8, also comprise SEQ ID NO: 2; however this is incoherent as no species of SEQ ID NO: 8 can also satisfy the sequence requirements of SEQ ID NO: 2 (RNAIA EIIKDI).
Claim 40 recites the polypeptides of claim 1 further consist of any combination of SEQ ID NOs: 1, 2, 3, 4, or 5, which is ambiguous or incoherent for use of the conjunction “or” denoting alternatives instead of “and” or “and/or” denoting combinations. Furthermore, even if claim 40 recites the polypeptides of claim 1, which each consists of one or more repeats of SEQ ID NO: 8, also must further consist of any combination of SEQ ID NOs: 1, 2, 3, 4, and 5; this is incoherent as no species of SEQ ID NO: 8 can satisfy the sequence requirements of SEQ ID NO: 1 (YIGSR), SEQ ID NO: 2 (RNAIA EIIKDI), SEQ ID NO: 3 (VGKKKKKKKKG), or any combination of the aforementioned.
Claim Rejections - 35 USC § 112(d) (maintained)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3, 29, and 44-45 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In claims 3, 44 and 45, the fusion proteins of claim 1 consisting of one or more repeats of SEQ ID NO: 8 are further limited to consist of at least a portion of an extracellular matrix component, growth factor and/or cytokine but in the form of a terminal protein fusion. Because claim 1 uses the phrase “consisting of,” there is a strong presumption this excludes all elements and components not specified in claim 1 and any claim which depends from claim 1 cannot add an element to said polypeptide(s) (see MPEP 2111.03). Because these claims encompass an entire growth factor, cytokine and/or extracellular matrix component not representable by [SEQ ID NO: 8]n, these claims are adding additional features to each fusion proteins of claim 1. A dependent claim of claim 1 cannot expand the fusion protein to have an additional feature(s) at an amino, a carboxy, or both the amino and carboxy ends of the polypeptides or fusion proteins already defined as “consisting of one or more repeats of a sequence (X1X2GXP)n (SEQ ID NO:8), wherein X1 and X2 are any amino acid, wherein X consists of tyrosine, alanine, or mixtures thereof, X1 and X2 can be the same or different amino acid, wherein n is equal to or greater than 1 and a whole numbers, and wherein during synthesis when Tyrosine and Alanine are a mixture at position X they are at a 1:4 ratio of Tyrosine to Alanine.”
Claim 29 expands the polypeptides of claim 1 consisting of one or more repeats of SEQ ID NO: 8 to “further comprise” SEQ ID NO: 3, which is not a repeat of SEQ ID NO: 8. Because claim 1 uses the phrase “consisting of,” it is read to exclude all elements and components not specified in claim 1 (MPEP 2111.03) and any claim which depends from claim 1 cannot add an element to the polypeptides limited as such.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant’s arguments of July 16, 2025 (pg. 8) are fully considered but not found to be persuasive regarding amended claims 3, 29, and 44-45 as set forth fully above.
Claim Rejections - 35 USC § 103 (new)
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, 3, and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Yeo (Yeo et al., Adv Healthc Mater 4: 2530-56 (2015)) in view of Paul (Paul et al., Soft Matter 13: 5665-75 (2017); IDS ref.) and Chen (Chen et al., Biomaterials 35: 675-83 (2014)).
Claim 1 is interpreted as explained in a prior section. Furthermore in claim 1, the “fusion proteins” are not required to be attached, coated on, or adhered to anything nor to be capable of differentiating cells.
Yeo teaches a 3D cell culture system comprising tropoelastin fragments or elastin-like peptides (ELPs) attached to a substrate (porous hydrogel) for use in culturing cells (Abstract; Tables 1, 3-4, 6; pg. 2534, left col., last para., to right col., last para.; pg. 2535, right col., 3rd para., to pg. 2536, right col., 1st para.; Fig. 5). Yeo teaches ELPs that are polypeptides or fusion proteins comprising a repeating pentapeptide from elastin, such using the pentapeptide motif GVGVP, which is a species of instant SEQ ID NO: 8, and can be in the form of a monomeric conglomerate of 5-10 repeats (pg. 2535, right col., 3rd para., to pg. 2536, left col., 1st para.; pg. 2538, right col., 1st para.). Yeo teaches engineered recombinant ELP hydrogels more closely resemble the charged, hydrated extracellular matrix (ECM) making them improved ECM-mimetic scaffolds compared to other 3D polymer materials, can provide larger porosity enhancing cell growth, and can be used as more favorable substrates for maintaining certain stem cells (pg. 2549, right col., para. 1-2; pg. 2544, right col., para. 2, to pg. 2545, left col., 1st para.; pg. 2537, right col., last para.; pg. 2533, right col., 3rd para.).
Yeo does not specifically teach the stem cells of the 3D cell culture system comprise iPSCs or ESCs.
However Paul teaches culturing stem cells on a hydrogel scaffold micropatterned with recombinant engineered ELPs to provide a cell-adhesive matrix mimicking a native tissue ECM, such as “wrinkled” patterns (Fig. 1; pg. 5674, left col., 1st para.; pg. 5666, left col., 1st para., and right col., 2nd para.; pg. 5672, left col.). Furthermore, Chen teaches culturing embryonic stem cells (hESCs) and pluripotent stem cells (hPSCs) on a biomimetic substrate with a wrinkled pattern to align the cells mimicking a cardiac tissue topography (Fig. 1; pg. 679, left col., 5th para.; pg. 680, right col., last para.).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing with the goal of culturing iPSCs or ESCs to select a recombinant ELP hydrogel comprising micropatterned ELPs as taught by Paul and Chen wherein the ELP consists of (GVGVP)n as taught by Yeo as a well-characterized type of synthetic ELP scaffold (pg. 2538, right col., 1st para.; pg. 2539, left col., 1st para.). One of ordinary skill in the art would be motivated to better mimic a natural extracellular matrix using micropatterns of elastin-like polypeptide as an ECM mimetic scaffold for cell adhesion and to select a common ELP repeat motif structure hydrogel known in the art as taught by Yeo as providing a better mimic to the charged, hydrated ECM and already known to be favorable substrates for culturing cells generally, such as an ELP consisting of 5-10 repeats of the GVGVP motif specifically taught by Yeo.
Regarding claim 3, Yeo teaches making ELP hydrogels comprising additional components, such as collagen, fibronectin, or hyaluronic acid (hyaluronan) for use as cell or tissue substrates (Table 6).
Regarding claim 44, Yeo teaches ELP based ECM-mimetic hydrogels for cell growth comprising a vascular endothelial growth factor (VEGF) polypeptide conjugated to an ELP component. Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing with the goal of making a cell culture scaffold to attach a VEGF polypeptide to an ELP and fuse the polypeptides at either an amino or carboxy end of the ELP as there are only a limited number of design choices for fusion positions while maintaining the continuous ELP and minimizing perturbing the ELP structure/function.
Regarding claim 45, Yeo teaches wherein the ELPs consist of repeats of the pentapeptide motif GVGVP, such as monomeric conglomerate of 5-10 repeats, which comprises at least a portion of a growth factor (G or V or P) and a portion of an ECM component (laminin).
Thus the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing absent evidence to the contrary.
Claims 1, 3-4, 40, and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Yeo in view of Paul and Chen as applied above, and further in view of Romano (Romano et al., Biochim Biophys Acta 1810: 339-49 (2011)).
Regarding claim 4, while Yeo teaches the carboxy-terminal end of an ELP having an elastin domain, the combination of Yeo, Paul and Chen does not teach wherein the ELP polypeptides of a hydrogel for use as cell culture scaffold comprise a fusion at an amino-terminal end to a laminin domain.
However Romano teaches the YIGSR motif of laminin provides a modular cell adhesive ligand for use in a cell culture substrate and that these laminin modules can be incorporated into recombinant proteins for cell adhesion (pg. 342, left col., 3rd para.), such as recombinant elastin-like polypeptides comprising repeating modular elastin domains include for hydrogel structural integrity (pg. 341, right col., 2nd para.; Fig. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to fuse the modular laminin motif taught by Romano (YIGSR) to the ELP of the ELP hydrogel taught by the combination of Yeo, Paul and Chen. One of ordinary skill in the art would be motivated to improve an elastin based ECM mimetic for use as a cell culture substrate by also including a laminin component, such as the modular laminin domain recognized by ECM cell surface receptors to promote cell adhesion to serve as a bioactive cell adhesion domain component for cell attachment during cell growth and proliferation as taught by Romano (pg. 342, left col., 3rd para.). Furthermore it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to fuse the modular laminin motif taught by Romano specifically to the amino-terminal end of the ELP because there is only a limited number of choices for fusion positions (namely two, either amino or carboxy terminal) while maintaining the core ELP polypeptide taught by Yeo.
Regarding claim 40, Romano teaches the YIGSR motif of laminin (instant SEQ ID NO: 1) provides a cell adhesive ligand as part of a cell culture substrate (pg. 342, left col., 3rd para.).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to fuse the modular laminin motif instant SEQ ID NO: 1 taught by Romano (YIGSR) to the ELP hydrogel taught by the combination of Yeo, Paul and Chen. One of ordinary skill in the art would be motivated to make an extracellular matrix mimetic for use as a cell culture substrate using an ELP-scaffold taught by Yeo combined with the modular laminin domain recognized by ECM cell surface receptors to promote cell adhesion to serve as a bioactive cell adhesion domain component for cell attachment during cell growth and proliferation as taught by Romano (pg. 342, left col., 3rd para.). Furthermore it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to fuse the modular laminin motif taught by Romano specifically to the amino-terminal end because there is only a limited number of design choices for fusion positions while maintaining the continuous ELP polypeptide taught by Yeo. Thus, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing absent evidence to the contrary.
Claims 1, 3, 31, and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Yeo in view of Paul and Chen as applied above, and further in view of Kiessling (US 20070207543 A1).
Regarding claim 31, the combination of Yeo, Paul and Chen does not teach wherein the ELP polypeptides further comprises instant SEQ ID NO: 2.
However Kiessling teaches instant SEQ ID NO: 2, as shown below, for use as an immobilized peptide domain that fosters the growth of stem cells (e.g., human H1 embryonic stem cells) on a substrate layer in culture, such as by providing cell adhesion (SEQ ID NO: 3; Abstract; [0050]; [0003]-[0004]; Examples).
CC PI Kiessling LL, Derda R, Orner BP, Thomson JA;
XX
DR WPI; 2007-717617/67.
XX
CC PT New array comprising self-assembled monolayer of molecular species,
CC PT useful for culturing cells in culture.
XX
CC PS Claim 17; SEQ ID NO 3; 26pp; English.
XX
SQ Sequence 11 AA;
Query Match 100.0%; Score 47; Length 11;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy SEQ ID 2 1 RNIAEIIKDI 10
||||||||||
Db 2 RNIAEIIKDI 11
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to fuse the modular cell adhesion peptide taught by Kiessling (instant SEQ ID NO: 2) to an ELP taught by Yeo to form a 3D hydrogel scaffold for adhesive human stem cell culture. One of ordinary skill in the art would be motivated to further include this specific cell module as an already validated adhesion domain for stem cell adhesion as taught by Kiessling. Thus, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing absent evidence to the contrary.
Claims 1, 3, and 41-45 are rejected under 35 U.S.C. 103 as being unpatentable over Yeo in view of Paul and Chen as applied above, and further in view of UniProt P15502 (UniProtKB Accession: P15502-3 (2018)).
Regarding claim 41, the combination of Yeo, Paul and Chen does not expressly teach wherein the ELP polypeptides consist of SEQ ID NO:70 and wherein in the sequence X1, X2, X3, X4, and X are any amino acid except proline.
However UniProt P15502 teaches the canonical human elastin isoform comprises multiple motifs encompassed by the genus of instant SEQ ID NO: 8: the motif PLGYP at position 223, the motif KAGYP at position 241, and the motif VPGAP at position 244.
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing with the goal of culturing human iPSCs or ESCs to use a naturally occurring human elastin motif, specifically any of the aforementioned pentapeptides of human elastin as taught by UniProt P15502 to construct an ELP consisting of 4 or more repeats of each of PLGYP, KAGYP, or VPGAP. One of ordinary skill in the art with the goal of culturing human cells would be motivated mimic a natural human ECM by using a human elastin ECM mimetic when constructing the 3D cell culture scaffold for use as a human cell culture substrate and to specifically use known human elastin repeating pentapeptide motifs, such as monomeric conglomerates of 5-10 pentapeptides from human elastin as taught by Yeo (pg. 2539, left col., 1st para.) and encompassed by instant SEQ ID NO: 70.
Regarding claims 42-43, Yeo teaches ELPs randomly constructed with 5-10 identical pentapeptide repeats from elastin, and UniProt P15502 teaches canonical human elastin comprises the pentapeptide VPGAP as noted above. Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing with the goal of culturing human cells to use 2-3 or more repeats of the naturally occurring human elastin pentapeptide VPGAP in the ELP, which constitute species of instant SEQ ID NOs: 71 and 73. Thus, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing absent evidence to the contrary.
Response to Arguments
Applicant’s arguments of July 16, 2025 (pg. 9-13) are fully considered but not found to be persuasive. As set forth fully above, the prior art of record in combination teaches all the limitations of the claims in the new grounds of rejection presented. The traversal based on a lack of teaching differentiating iPSCs or ESCs into cardiomyocytes is not persuasive when this is not interpreted as a limitation but merely an intended use based on the wording of the product claims and also is considered an inherent functionality of the structures positively recited in the product claims. Similarly, there is no limitation that “wherein during synthesis when Tyrosine and Alanine Y and A are a mixture at position X they are provided at a 1:4 ratio of Tyrosine to Alanine” as argued.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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/ERIC J ROGERS/
Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638