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 1-19 are pending in the application.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1-12, in the reply filed 6/1/26 is acknowledged as well as the species of peptide comprising SEQ ID NO: 2. The traversal is on the ground(s) that unity of invention under PCT Rule 13.1 exists over Yang. This is not found persuasive for reasons of record and below because the shared technical feature of a hydrogel comprising gelatin and a peptide according to the parameters recited in claim 1 does not make a contribution over the prior art in view of Yang teaching hydrogels comprising gelatin and a peptide according to instant claim 1. The election/restriction is deemed proper and is therefore made final. Claims 13-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Objections to the Disclosure
Drawings FIG. 6A, FIG. 6B, FIG. 9, and, [0029] and [0075-[0076] in the specification each refers to colors (e.g., red, green and blue); however, color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 will not be held in abeyance.
This application contains an attempted sequence disclosure in the form of sequence referent SEQ ID NO: 16 at instant [0012] (see MPEP §§ 2412.05(a), 2422). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834 regarding SEQ ID NO: 16. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Interpretation
In the claims, the term “peptide” is interpreted in view of the specification as being linear and about 10 kDa or less but including sizes of 154 amino acid residues or more, such as 30 kDa peptides in gelatin, in view of the art (Ridgley et al., Biomacromolecules 12: 3770-9 (2011) at Table 3; Liu et al., at pg. 12, last para.). Note in claim 3, the peptide comprising “8 or 12 amino acids” means the “sequence” has at least 8, 10 or 12 amino acids, but optionally having 2 amino acids unlimited by the claim 1 limitations to said sequence.
In the claims the term “gelatin” is interpreted as meaning any unmodified proteinaceous component of a known gelatin as of the instant filing date, as sources and types of gelatin vary, e.g., due to extraction/isolation processes like chemical hydrolysis, pressurization, or proteolysis (see e.g., Rather et al., “A comprehensive review on gelatin,” Food Packaging and Shelf Life 34: 100945 (2022) at Table 1; pg. 2, left col., last para. to pg. 3, left col., Fig. 1).
In claims 9-12, the hydrogel is interpreted as being at least partially hydrated as it is noted that a hydrogel is a network of polymers that can retain large volumes of fluids, which can greatly affect the total weight of hydrogel having the same weight percent of a component.
Claim Rejections - 35 USC § 112(a), Written Description
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 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of.
Claim 1 is direct to a gelatin-comprising hydrogel also comprising a peptide comprising a sequence having at least eight amino acids with alternating hydrophobic amino acids (e.g., X1, X2, X3, and X4) and hydrophilic amino acids (e.g., Y1, Y2, Y3, and Y4) wherein there is at least one R and K, such as represented by the following wherein at least one Y is an R and at least one other Y is a K:
X1Y1X2Y2X3Y3X4Y4 or
Y1X1Y2X2Y3X3Y4X4.
In claim 1, the peptide is defined at a high level of generality in that it must merely comprise the more precisely limited peptide sequence but can further comprise one or more unlimited additional sequences. Furthermore, the claimed hydrogel is also described at a high level of generality in that the gelatin and peptide components are not limited by any relationship to each other, any relative amount or to the composition of the polymer, i.e., does the bulk polymer of the hydrogel comprise either gelatin and/or the peptide?
The prior art teaches hydrogels can be either non-peptide based (e.g., protein-based) or peptide-based wherein the bulk polymer network of the hydrogel comprises cross-linked peptides or otherwise physically intertwined molecules comprising peptides (Jonker et al., Chemistry of Materials 24: 759-73 (2012) at pg. 762-770, Fig. 4-5, 8-10, 12-13). The prior art teaches some peptides (e.g., KLDLKLDLKLDL) can self-assemble into hydrogels (e.g., FEK16 or KLD-12) based on ion or pH conditions (Jonker at Fig. 9, pg. 767, right col., 2nd para.; pg. 765, last para.; Kisiday et al., PNAS 99: 9996-10001 (2002)). The prior art also teaches gelatin is a naturally occurring proteinaceous substance related to collagen, which encompasses different single-stranded degradation products of collagens (partial hydrolysis), including gelatin types A and B (Jonker at pg. 760, last para., to pg. 761). Gelatin can be crosslinked to form hydrogels, such as a gelatin hydrogel cross-linked using 1 mM 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) which later had MMP-2 added resulting in peptides forming in the hydrogel (Lai and Li, Biomacromolecules 11: 1387-97 (2010) at Fig. 7).
Thus, a collagen-based hydrogel could further comprise a peptide or a peptide-based hydrogel could further comprise gelatin peptides, wherein the additional component is not part of the bulk polymer network, e.g., not cross-linked to the predominant polymer component. Alternatively, both the gelatin and peptide components of a hydrogel could be part of the bulk polymer network, i.e., physically linked in some manner.
In view of the instant specification, some peptides can self-assemble into hydrogels, e.g., SEQ ID NO: 1 (EAK16), and the goal of the invention appears to be to provide novel self-assembling peptides, such as for use in making cell culture scaffolds and/or in vivo grafts ([0006], [0045]). To this end, the specification describes SEQ ID NO: 2 (IVK8) as a “novel” self-assembling peptide (FIG. 1, [0065]), including biocompatible hydrogels comprising this peptide and gelatin ([0065]-[0067], Table 1) as well as describing SEQ ID NOs: 3-8 as self-assembling peptides based on WO2021015675 (Yang). Furthermore, the description describes peptide/gelatin hybrid gels as useful for cell-culture applications because it can mimic a natural basement-membrane matrix scaffold, but these hybrid gels are advantageously be formed specifically from only two components: (1) a short 8 or 12 amino acid self-assembling peptide and (2) gelatin whereby the peptide self-assembles into a matrix with a high propensity and the gelatin provides cell adhesion moieties ([0045]-[0048]).
Importantly, the specification discusses the importance of having no strong charge at the self-assembling peptide terminals to minimize charge repulsion, such as either a hydrophobic N-terminus or an acetylated residue at the N-terminus and an amidated C-terminal residue ([0046], [0067]). The specification also notes that gelatin hydrogels formed by chemical crosslinking may suffer from poor reproducibility due to the manufacturing process and the inherent heterogeneity of gelatin components ([0048]) while synthetic peptide-based hydrogels with cell adhesion moieties (e.g., functionalized with fibronectin peptides) may support cell growth but with limits ([0006]).
Therefore, in view of the instant specification, the only hydrogels taught comprising a peptide and gelatin are hybrid made with no other components and incorporating a self-assembling peptide and gelatin wherein the gel is peptide-based and the gelatin (e.g., at 2-3%) is not crosslinked using any chemical reagent/catalyst but rather is merely present during the self-assembly of the so-called peptide component into a hydrogel based on an increase in temperature ([0050], [0045]). Further, all the representative species of peptides either having no strong charge at the self-assembling peptide terminals due to the unmodified peptide residue and/or acetylated N-terminal residue and/or an amidated C-terminal residue. The peptide genus encompassed by the claims includes 50 amino acid peptides having a required sequence of only eight amino acids, leaving 42 amino acids of unlimited sequence.
Regarding the sequence of the self-assembling peptide, all the 14 representative species provided in the description (SEQ ID NO: 2-15) are “short,” either 8 or 12 amino acids in total length, and this is noted as the preferred size ([0009]), perhaps due to improved cell viability and/or clarity ([0080], [0050). Moreover, the prior art teaches self-assembling peptides cannot be too long/large or short, e.g., Yang teaches self-assembling peptide length dictates the strength of intermolecular and intramolecular interactions (pg. 32, last para., to pg. 33, 3rd para.) and, thus, the prior art is conspicuously silent as to any self-assembling peptides greater than about 45-50 residues or over about 6 kDa due to challenges for desired secondary structure formation and precipitation/aggregation over soluble controlled assembly (see e.g., Ayanda et al., J Biol Sci. 22: 309-32 (2022) at pg. 315, right col., 2nd para., to pg. 317). Furthermore, self-assembling peptides rely on the property of amphiphilicity, meaning an additional sequence(s) in the peptide should not be either completely hydrophobic or hydrophilic, i.e., needs to maintain something akin to the alternating R-group pattern recited in the sequence in claim 1.
The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of the entire scope of all hydrogels comprising gelatin and one of said peptide, which encompasses peptides having any sequence without limit so long as comprising the recited subsequence.
35 USC § 112(a), Scope of Enablement
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because while enabling for wherein the peptide is less than 45 amino acids long and interlinked with proteinaceous gelatin components (i.e., co-gelated); the specification does not enable any person, skilled in the art to which it pertains, or with which it is most nearly connected to, to make the hydrogel over the entire scope of peptides comprising at least 8 amino acids with no maximum and which are unlimited in their relationship to the gelatin.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue.' Not 'experimentation;" (Wands, 8 USPQ2d 104). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighting many factual considerations." (Wands, 8 USPQ2d 1404).
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Furthermore, the USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims
Claim 1 is directed to a product, a hydrogel, comprising a peptide and gelatin. As gelatin is a collection of peptides from collagen, all hydrogels comprising gelatin also comprise a peptide, and gelatin alone can be made into a hydrogel. However, there is no currently known gelatin peptide according to the peptide limitations recited in claim 1 but research is ongoing (see ). Thus, at least one additional peptide must be present in the claimed product.
Claim 1 may also be considered a product categorized by the arrangement/organization/interactions of the components of the hydrogel, in other words a product made via interactions between the so-called peptide and the gelatin component (i.e., gelatin peptides). As such interactions are not required in the claims, in order to make/use the claimed product, a person of ordinary skill in the art would need to be able to form a hydrogel using these two components. For example, the hydrogel could be based predominantly on the peptide and merely be seeded with the gelatin component or vice versa. Dependent claims 9-10 seem to encompass the former whereas dependent claims 11-12 allow for the later.
The state of the art:
The prior art teaches hydrogels made with gelatin as well as self-assembling peptides (SAPs) that form hydrogels, particularly peptides consisting of alternating hydrophilic and hydrophobic amino acids (Jonker at pg. 761, left col.; pg. 765-768). For example, the prior art teaches how to control the properties of hydrogels made with SAPs, such as in relation to ionic and/or pH conditions and the influence of peptide properties on secondary structure during gelation, e.g., isoelectric points (Sun et al., Biomed Mater 12: 015007 (2017) at pg. 2, left col.; pg. 9, right col.). The prior art teaches design strategies for SAPs include (i) alternating hydrophobic and hydrophilic sides, (ii) alternating positively charged and negatively charged residues, and/or (iv) alternating polar and nonpolar sides, such as to form either α-helical or β-sheet hydrogel materials due solely to non-covalent interactions (Gelain et al., Chem Rev 120: 13434-60 (2020) at pg. 13435-6). Gelain notes that if the SAP has too many hydrophobic residues, the peptide would become water-insoluble and precipitate out of solution whereas if there are too many hydrophilic residues, the peptide will be highly water-soluble, thus the hydrogel is unable to form (pg. 13437).
However the prior art is silent as to reliable forming a hydrogel from non-self-assembling peptides for biomedical applications like cell culture or tissue engineering. These aspects of using must be shown to a reasonable extent so that one of the ordinary skills in the art would be able to practice the invention without any undue or unreasonable burden being on such artisan.
The amount of direction and guidance as well as any working examples provided:
The instant specification provides working examples of peptides according to claim 1 in instant SEQ ID NOs: 2-15, which are all short and self-assembling, either 8 or 12 amino acids in total length ([0065]-[0068]; FIG. 1-2, 10-11 and 14),and further the guidance in the specification notes this is the preferred size ([0009]) without guidance as to any large peptide design or adaptation for larger-formats. Nowhere does the instant specification show how to perform make a working embodiment without at least 0.25 % weight of self-assembling peptide and at least 0.25 % weight gelatin.
Thus, there is no evidence in the instant application or the prior art that hydrogels over the scope of peptides encompassed by the claims: i.e., regarding length/size, self-assembling properties or lack thereof, and additional sequences. Nowhere does the instant specification show how to make a hydrogel with a peptide that is not considered self-assembling, is not shorter than 14 amino acids and does not comprise sequences other than instant SEQ ID NO: 2-15, such as sequences that do not follow the generic/consensus formula of the sequence of claim 1.
Undue experimentation would be required to fill these gaps and unpredictability, especially for three factors simultaneously. Undue experimentation is required to determine the how to achieve a hydrogel despite the ease of mixing the required components encompassed by the claims, and may never actually be achievable across the full scope peptides.
In summary, the claims are rejected under 35 U.S.C. 112(a) because the specification does not reasonably provide enablement to a person skilled in the art to produce hydrogels with such a wide breadth of peptide components in view of the instant specification. Given the lack of working examples, the limited guidance provided in the specification, the lack of guidance in the prior art, and the broad scope of the claims with regard to the peptide component, undue and/or unreasonable experimentation would have been required for one skilled in the art to produce hydrogels over the full scope claimed.
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.
Claim 8 is 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 pre-AIA the applicant regards as the invention.
Claim 8 recites wherein the sequence comprises SEQ ID NO: 16; however, the disclosure is silent as to any sequence for SEQ ID NO: 16. Thus, claim 8 is indefinite at the term/referent “SEQ ID NO: 16.” For purposes of examination herein, claim 8 was instead interpreted as encompassing exclusively SEQ ID NOs: 2-15.
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 1-6 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (WO2021015675A1, priority to 2020-7-22).
The claims are interpreted as provided in a previous section.
Yang teaches hydrogels comprising self-assembling short peptides (pg. 7, lines 1-2) having an alternating sequence of hydrophobic (X) and (Y) hydrophilic amino acids, wherein each hydrophobic amino acid is independently selected from isoleucine (I), valine (V) and leucine (L); each hydrophilic amino acid is independently selected from arginine (R), lysine (K), glutamic acid (E), and aspartic acid (D); at least one hydrophilic amino acid is selected from arginine and lysine; at least one hydrophilic amino acid is selected from glutamic acid and aspartic acid; and the amino acid sequence contains an even number of amino acids and at least 8 amino acids, such as precisely 8 or 12 amino acids (abstract, pg. 3, lines 21-28; pg. 4, line 11, to pg. 6, line 22; pg. 42, 1st para.). More particularly, Yang teaches hydrogels comprising peptides related to SEQ ID NOs: 8-26, such as IRIKIRIK (“IK8L” (SEQ ID NO: 17)) and IRIKIEIEIRIK (“IIK12” (SEQ ID NO: 16)), which can be represented respectively as X1Y1X2Y2X3Y3X4Y4 and X1Y1X2Y2X3Y3X4Y4X5Y5X6Y6 where X is I and each Y is either R, K or E (pg. 6, lines 19-22; pg. 23; Table 1). Yang further teaches hydrogels comprising such peptides and gelatin for use in making pharmaceuticals with prolonged absorption of an active ingredient due to the presence of the gelatin (pg. 19, lines 27-29), such as wherein the hydrogel comprises a specific therapeutic peptide (e.g., IRIKIRIK) (pg. 7, lines 29-30 and lines 10-11). Thus, the subject matter of claim 1 is taught by Yang to one of ordinary skill in the art before the effective time of filing.
Regarding claim 1, Yang also teaches such self-assembling peptide hydrogels comprising gelatin for use in making synthetic polymer scaffolds for tissue engineering (pg. 1, lines 13-16). Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to make a peptide-based hydrogel according to the parameters of Yang as a cell support for tissue engineering, such as wherein the peptide consists of any of SEQ ID NOs: 8-16 and 19-26. One of ordinary skill in the art would be motivated to make this hydrogel for use as a biocompatible polymer scaffold for tissue engineering wherein the peptide provides a structural matrix and the gelatin provides favorably recognition by host cells (pg. 1, lines 13-16).
Regarding claim 2, Yang teaches wherein the peptide comprises two or more glutamic acids, as in any of SEQ ID NOs: 8-26 (pg. 6, lines 19-22; pg. 23; Table 1).
Regarding claim 3, Yang teaches wherein the peptide comprises 8, 10, or 12 amino acids (pg. 4, lines 13-14, claim 4).
Regarding claim 4, Yang teaches wherein the peptide’s alternating pattern comprises four hydrophilic amino acids (Y1, Y2, Y3 and Y4) such that Y1 and Y2 are selected independently from glutamic acid and aspartic acid, and Y3 and Y4 are each independently selected from arginine and lysine (pg.4, lines 19-24).
Regarding claim 5, Yang teaches wherein the peptide is as recited in the claim, e.g., in peptides comprising the sequence IEVEIRVK (SEQ ID NO: 10), IEIEIRIK (SEQ ID NO: 11) or IELEIRLK (SEQ ID NO: 12).
Regarding claim 6, Yang teaches wherein the peptide is as recited in the claim, e.g., in ones comprising the sequence IRVKIEVEIRVK (SEQ ID NO: 15), IRIKIEIEIRIK (SEQ ID NO: 16), or KIRIEIEIKIRI (SEQ ID NO: 20).
Regarding claim 8, Yang teaches wherein the comprises instant SEQ ID NO: 2 in teaching IVK12 (SEQ ID NO: 15) as shown below, which was amidated at the C-terminus for making hydrogels (pg. 7, lines 15; Table 1, FIG. 2A, pg. 29, line 25, to pg. 26, line 11).
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
# Length: 8
# Identity: 8/8 (100.0%)
# Similarity: 8/8 (100.0%)
# Gaps: 0/8 ( 0.0%)
# Score: 36.0
SEQ2 1 IEVEIRVK 8
||||||||
Yang 5 IEVEIRVK 12
Regarding claims 9-10, Yang teaches wherein the peptide is present in the hydrogel at a concentration of 0.5-2.0, such as at 0.6%, 1%, 1.5% or 1.75% (Table 2-3). Note, a prima facie case of obviousness exists when the claimed range overlaps values disclosed in the prior art (see MPEP 2144.05).
Claims 1-7 and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Ellis (US 20080274979 A1) in view of Yue (Yue et al., Biomaterials 73: 254-71 (2015)).
Ellis teaches self-assembling peptides for making hydrogels wherein the peptides having at least 8 or 12 amino acid residues with alternating hydrophilic and hydrophobic parts according to their Formulae I-IV, such as peptides comprising VRVEVRVEVRVE (SEQ ID NO: 207) or IRIEIRIEIRIE (SEQ ID NO: 239), as shown below aligned with instant SEQ ID NO: 7 ([0049]-[0051], claim 4; Table 3). Formulae I, for example, encompasses peptides comprising beginning with sequences (Xaaneu-Xaa+)4 which can be categorized as X1Y1X2Y2X3Y3X4Y4, wherein each X (Xaaneu) may be I, V, or L and each Y (Xaa+) may be R or K. Ellis teaches using hydrogels made from such self-assembling peptides as synthetic extracellular matrices to stabilize cells or tissues, such as formulated with collagen ([0061], [0118], claim 1).
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
# Length: 12
# Identity: 9/12 (75.0%)
# Similarity: 12/12 (100.0%)
# Gaps: 0/12 ( 0.0%)
# Score: 51.0
SEQ7 1 IRVEIRVEIRVE 12
:|||:|||:|||
Ellis 1 VRVEVRVEVRVE 12
#=======================================
# Length: 12
# Identity: 9/12 (75.0%)
# Similarity: 12/12 (100.0%)
# Gaps: 0/12 ( 0.0%)
# Score: 51.0
#
#
SEQ7 1 IRVEIRVEIRVE 12
||:|||:|||:|
Ellis 1 IRIEIRIEIRIE 12
Ellis does not teach wherein the hydrogel specifically comprises gelatin.
However Yue teaches gelatin containing hydrogels are a commonly used for biomedical applications due the biological properties of gelatin, such as excellent biocompatibility, low immunoresponse, solubility, gelation at low temperature, and less antigenicity (Abstract; pg. 254, to pg. 255, left col.). Furthermore, Yue teaches gelatin hydrogels comprising gelatin mixed with peptides (hybrid hydrogel systems) for specific biological applications, such as cell proliferation, differentiation, and/or tissue engineering (Abstract, Fig. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to make a peptide-based hydrogel according to the parameters of Ellis as a cell support for tissue engineering, such as wherein the peptide comprises VRVEVRVEVRVE or IRIEIRIEIRIE as taught by Ellis and further comprising gelatin as taught by Yue. One of ordinary skill in the art with the goal of making a synthetic matrix mimicking a natural extracellular matrix suitable for stabilizing animal cells would be motivated to add gelatin as taught by Yue for its desirable gel properties in biomedical applications.
Regarding claim 2, Formulae I-IV of Ellis encompass peptides as above and further comprising either before or after the aforementioned sequence the additional sequence XnYn wherein n is an integer 1-4 and each X (Xaaneu) may be I, V, or L and each Y (Xaa-) may be D or E.
Regarding claim 3, Ellis teaches wherein the peptide has 8 or 12 amino acid residues, e.g., preferably 8-16, 8-24, or 12-20 residues ([0036]). Note, a prima facie case of obviousness exists when a claimed value is overlapped by a range disclosed in the prior art (see MPEP 2144.05).
Regarding claims 4-5, Formulae IV of Ellis encompass peptides as above and further comprising either before or after the aforementioned sequence the additional sequence XnYn wherein n is 2 and each X (Xaaneu) may be I, V, or L and each Y (Xaa-) may be D or E, including wherein Xaa- is always E, x=2, y=2 and n=1 in ((Xaa−−Xaaneu)x((Xaa+−Xaaneu)y)n.
Regarding claim 6, Formula IV of Ellis encompass peptides as above wherein x is 2 and y is 4 and each Y (Xaa-) may be D or E in ((Xaa−−Xaaneu)x((Xaa+−Xaaneu)y)n or alternatively as in Formula III of Ellis wherein x is 2 and y is 2 in ((Xaa+−Xaaneu)x(Xaa−−Xaaneu)y)n.
Regarding claim 7, Formula IV of Ellis encompass peptides as above wherein n is 1, x is 2 and y is 4 and each Xaa- is D and each Xaa+ may be R or K in ((Xaa−−Xaaneu)x((Xaa+−Xaaneu)y)n as in claim 7 (Y1XY2XY3XY4XY5XY6X).
Regarding claims 9-10, Ellis teaches wherein the amount of peptide is approximately 0.1% (e.g., about 0.1%-5%; 0.5%-5%; 1.0%; 1.5%; 2.0% or 0.1-1.0%; 1.0-2.0%) ([0087]). Note, a prima facie case of obviousness exists when the claimed range overlap ranges disclosed in the prior art (see MPEP 2144.05).
Regarding claims 11-12, Yue teaches hydrogel gelatin concentrations of 5%, 8% or 10%, such as hybrid gelatin hydrogels with 5 (w/v%) gelatin (Fig. 1, pg. 256, left col., 2nd para.; pg. 261, right 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 make a peptide-based hydrogel according to the parameters of Ellis as a cell support for tissue engineering, such as wherein the peptide comprises VRVEVRVEVRVE or IRIEIRIEIRIE as taught by Ellis and further comprising gelatin at 5 weight% as taught by Yue. One of ordinary skill in the art with the goal of making a synthetic matrix mimicking a natural extracellular matrix suitable for stabilizing animal cells would be motivated to add gelatin at already validated percentages as taught in the prior art.
Thus, the claimed invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective time of filing in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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