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 .
Response to Amendment
Applicant's amendment and argument filed 11/12/2025, in response to the non-final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 1, 14-16, 29-32, 35-37, 40-42, 55 and 65-66 are pending in the instant application. Claim 55 has been withdrawn. Claims 1, 14-16, 29-32, 35-37, 40-42 and 65-66 are being examined on the merits.
This rejection is maintained due to the amendments and arguments filed on 11/12/2025.
Nucleotide and/or Amino Acid Sequence Disclosures
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 deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specific deficiencies and the required response to this Office Action are as follows: There are no sequence listings for Figure 60, of which describes a list of miRNA sequences that are being claimed.
Examiner’s note for applicant from MPEP:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim. See MPEP § 608.01(m) for information pertaining to the treatment of reference characters in a claim.
Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing," in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5) ), preceded by "SEQ ID NO:" or the like, in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5) ), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.823(a)(5) ) in the Brief Description is clear.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 29 is 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 claims limitations are directed to a list of miRNAs which there are no described sequence listings in computer readable format and thus persons having ordinary skill in the art would not be able to discern what the process is for making and using the claimed invention. MPEP 2161 1. recites “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. In this case the miRNAs being claimed do not have searchable sequence identifiers and there is no description to what the sequences of these specific miRNAs are. Persons having skill should not have to rely on a separate database, website, etc. in order to interpret what the applicant is intending for the claim limitations. These need to be described in the instant invention.
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 29 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claim is indefinite because it is not known what are the exact sequences of the miRNAs being referenced and claimed from Figure 60 as described in the invention (specifications/claims/drawings) and this makes the claim confusing.
Response to Arguments
Applicant's arguments filed 11/12/2025 have been fully considered but they are not persuasive. The applicant argues that it would be impractical to incorporate the list of miRNAs in claim 29 because the list contains accession numbers and unique identifiers. The applicant needs to amend the specifications and claims to incorporate sequence identifiers as previously/currently discussed. Many miRNAs may have single nucleotides that differ allowing variations from the miRNA common names. It also is not understood if the miRNA recited is to the gene, the hairpin structure, the transcript or the mature structure. This is the reason for having SEQ IDs so that there is no need for additional interpretation and/or ambiguity.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 1, 29-32, 35-37, 40-42 and 66 are rejected under 35 U.S.C. 103 as being unpatentable over John Sinden et. al. (US20150079046A1), Sgambato et. al. (Bioresponsive Hydrogels: Chemical Strategies and Perspectives in Tissue Engineering, Gels, 2016, 2, 28), Maldonado-Lasunción et. al. (Mesenchymal Stem Cell-Macrophage Choreography Supporting Spinal Cord Repair, Neurotherapeutics, May 4, 2018, 15:578-787) and Jieli Chen and Michael Chopp (Exosome Therapy for Stroke, Stroke Vol 49, No 5, April 2018), hereinafter Chen. This is a new rejection based on the amendments filed on 11/12/2025.
Regarding claim 1, Sinden teaches of compositions which comprise of neural stem cell microparticles for promoting neurogenesis, neuroprotection and/or neurological diseases (see 0011), and wherein in one aspect of the invention, conditionally immortalized stem cells are used to produce microparticles such as microvesicles and/or exosomes. These conditionally immortalized stem cells are typically neural stem cells, but may be a stem cell of any type, for example a haematopoietic stem cell or a mesenchymal stem cell (see 0205). Sinden also teaches wherein these compositions can be used for neurological disorders such as stroke (see claim 16).
Sinden teaches the neural stem cell microparticles of the invention may express one or more miRNAs (including miRNA precursors) at a level which is lower or higher than the level of expression of that miRNA (including miRNA precursors) in a mesenchymal stem cell microparticle of the same species (see 0079).
Sinden teaches the pharmaceutically acceptable composition typically includes at least one pharmaceutically acceptable carrier (see 0160).
Sinded teaches mature miRNA’s with GGAG sequence at the 3’ end of mature miRNAs (see 0105-0106, 0309, table 4-9,), and this would indicate a mature miRNA engineered to comprise a genetic tag that triggers the cell to take that miRNA into the exosome, because as the applicant recites in their own specification at page 46, “recent studies on miRNA sorting into exosomes have identified a target sequence in the 3' end of miRNAs (GGAG; SEQ ID NO:8) that directs exosomal sorting and are available as expression systems (System Biosciences, XMIR expression system) directing miRNA into exosomes”. Sinden teaches the same GGAG motif for miRNA sorting.
Regarding claims 14-16, Sinden teaches wherein the miRNAs present in the microparticles as determined by qRT-PCR would be has-miR-424 and has-let-7a and these are recognized by the applicant to bring about the upregulated and downregulated activities as claimed (see specifications at 0114).
Regarding claim 29, Sinden teaches wherein the miRNAs present in the microparticles as determined by qRT-PCR would be has-miR-424 and has-let-7a and these are recognized by the applicant to bring about the upregulated and downregulated activities as claimed (see specifications at 0114).
Sinden does not teach wherein the carrier is a hydrogel comprises a plurality of biocompatible polymers or oligomers cross-linked with a hydrolysable linker, and wherein the linker comprises an acrylate or methacrylate, and optionally an ester, amide or a combination thereof. Sinden also does not specifically teach wherein the composition decreases the ratio of pro-inflammatory M1 macrophages to anti-inflammatroy M2 macrophages relative to the ratio demonstrated by the activity of naturally occurring cell-derived exosome when a therapeutically effective amount of the composition is administered to a subject in need thereof and wherein the therapeutically effective amount of the composition administered to a subject in need thereof is a dosage of 1x106 to 1x1012 exosomes per unit mm3 of graft, tissue, patch or injection volume are administered.
Sgambato’s general disclosure is a review on bioresponsive hydrogels (see abstract).
Regarding claims 1 and 31-32, Sgambato teaches “The design and development of new cell-customized biomaterials able to mimic extracellular matrix (ECM) functionalities represents one of the major strategies to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during the regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions” (see abstract).
Sgambato teaches “Alginates are composed of guluronic acid and mannuronic acid. Their abundance, and low prices, allow a wide spread use in the food industry as thickeners, emulsifiers, and in tissue engineering applications. Alginate was also used for various biomedical applications, such as drug delivery and cell encapsulation, because it is able to gel under mild conditions by the addition of divalent cations, it is biodegradable, and has low toxicity. Alginate-based hydrogels have also been obtained by chemical cross-linking by adipic hydrazide or PEG using carbodiimide chemistry” (see page 2, 2.1).
Regarding claim 1 Sgambato teaches “In fact, synthetic hydrogels can be designed using polymers with controlled molecular weight and biodegradable linkers. These features allow for the fine tuning of hydrogel composition, formation dynamics, mechanical properties, and degradation rates” and “Usually PEG acrylates or methacrylates can be photopolymerized, affording controlled hydrogel architectures” (see page 2, 2.2)
Regarding claim 35, Sgambato teaches “EphA receptor and ephrinA5-Fc ligand are cell surface-bound proteins involved in, among other things, insulin secretion from pancreatic β-cells promoting cell adhesion and motility/morphology changes through the integrin signaling pathway. These bioresponsive hydrogels were shown to provide crucial cell-cell communication cues for cell survival and proliferation” (see page 4, 4.1).
Regarding claim 36, Sgambato teaches “Hydrogels made up of naturally derived components, for example extracellular matrix proteins (such as collagen) and polysaccharides like GAGs, have received particular attention in different applications in the field of regenerative medicine, since they supply physico-chemical and biochemical features that are similar to the native cellular milieu” (see page 4, first para.).
Regarding claim 37, Sgambato teaches “The bioconjugation of peptides in place of full-length proteins greatly simplifies the chemistry and may improve the efficacy of the bioconjugation. Since many mammalian cells are anchorage-dependent, cell adhesive properties of the hydrogel can be achieved by the introduction of small adhesive peptidic sequences into the hydrogel matrix; for example, they can be derived from laminin, such as RGD(Arg-Gly-Asp), LGTIPG, YIGSR, IKVAV, LRE, PDGSR, IKLLI, LRGDN, and from type I collagen and fibronectin, in other words, DGEA, KQAGDV, REDV, and PHSRN” (see page 6, 4.2).
Maldonado-Lasunción’s general disclosure is a report on how MSCs are known to benefit the repair of damaged spinal cord (see absatract).
Maldonado-Lasunción teaches that “many of these paracrine MSC-mediated events result in neuroprotection, which may be associated with functional recovery [10, 83, 84]. Evidence in the literature shows that an intraspinal MSC transplant leads to a decrease in apoptotic neural cell death [16, 85] and in overall neurotrophic support of the damaged tissue” “MSCs are known to affect the profile of the inflammatory response through modulation of the macrophage phenotype”
“Inflammatory cues in an injury microenvironment are sensed by MSCs that, in response, produce cytokines that modulate macrophages to express their anti-inflammatory, pro-reparative, phenotype, which supports restoration of homeostasis and promote tissue repair” (see page 581, Reparative Properties of MSCs in the Injured Spinal Cord).
Maldonado-Lasunción teaches “MSCs constitutively secrete immunosuppressive cytokines, such as TGFβ, IDO, NO, TNF-inducible gene-6 (TSG-6), prostaglandin-E2 (PGE2), and anti-inflammatory ILs that induce modifications in the metabolism of macrophages, resulting in a switch to the anti-inflammatory macrophage phenotypes [23, 24, 92, 96, 106] (Fig.1). When cultured with MSC-conditioned medium, macrophages polarize showing increased expression of M2-like surface markers and reduced secretion of the inflammatory cytokines, IL1β, IL6, and TNFα [92]. Macrophages in culture with MSC spheroids, which secrete enhanced levels of PGE2, or with conditioned medium thereof, polarize from M1-like to M2-like macrophages [107, 108]” (see page 582, MSCs Modulate Macrophage Polarization).
Maldonado-Lasunción teaches that “Inflammation and macrophage-derived cytokines influence the secretory profile of MSCs [12, 24, 79]. It was found that in vitro exposure to macrophage-conditioned media, as well as coculture with different phenotypes of macrophages, modifies the secretome of MSCs and their viability for cardiac tissue repair [27]. Crisostomo and colleagues used inflammatory stimuli, such as TNFα and lipopolysaccharides (LPS), to condition MSCs and found an increase in the secretion of growth factors that support tissue repair [12].” (see, bottom right of 582 to left side of 583).
“Effective immunomodulation by MSCs occurs upon exposure to activating stimuli. Under stress conditions, MSCs are programmed to increase their secretion of growth factors. For instance, MSCs in culture under hypoxic conditions produce enhanced levels of growth factors [12]. Cultured MSCs exposed to inflammatory molecules increase the expression of receptors known to bind immune regulatory mediators and the production and secretion of anti-inflammatory factors” (see MSC Immunomodulation Requires Activation, page 583).
Chen’s general disclosure is a scientific report about exosomes as a means for stroke therapy (see first para. page 1083).
Chen teaches “neural released exosomes not only regulate the onset and progression of neurodegenerative and neuroinflammatory diseases but also may play a role in the regeneration and remodeling of the nervous system after stroke. Neural secreted exosomes contribute to local synaptic plasticity and also influence neuronal networks by long-range communication within the central nervous system. Therefore, by inhibiting their release from diseased cells and by manipulating their cargo to enable shuttling of secretory RNA, miR, or molecules such as cytokines, chemokines, and growth factors, exosomes may function as therapeutic agents” (see page 1085, first para.).
“Using stem cell–secreted paracrine factors and cell-free therapy are likely safer alternatives in promoting brain plasticity after stroke and in neurodegenerative disease. Recently, a variety of cell types have been shown to secrete paracrine factors that are contained within membrane vesicles, such as exosomes, microvesicles, ectosomes, membrane particles, and apoptotic bodies. Extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells. Treatment of stroke and neural injury with extracellular vesicles, that is, exosomes, harvested from MSCs, rather than the exosome parent MSCs, supplants the therapeutic benefits of administration of the parent MSCs. Exosomes are specifically internalized by recipient cells, which avoids a multiplicity of potential concerns associated with administration of living cells, and exosomes provide therapeutic benefit, at least the equivalent of their cellular source. Compared with cell therapy, the advantages of exosome-based therapy include (1) low immunogenicity; (2) no vascular obstructive effect and reduced risk of secondary microvascular thrombosis; (3) systemically injected exosomes are able to cross the blood–brain barrier and enter the brain parenchyma; (4) the potential to develop large-scale cellular factories of engineered therapeutic vesicles; (5) exosomes have higher surface/volume ratio and amplify ligand-gated signaling pathways and the transfer of biomolecules from stem cells to target tissues; and (6) ability to readily modify exosome miR content” (see page 1085, Advantages of Using Stem Cell–Derived Exosomes for Stroke Therapy).
“MSC-Exos taken up by endothelial cells, dose dependently increase endothelial cell proliferation, migration, and capillary tube formation, as well as impair T-cell function by inhibiting T-cell proliferation in vitro. Systemically injecting bone marrow–derived MSC-Exo at 1 day after ischemic stroke or traumatic brain injury significantly improves functional outcome, as well as enhances angiogenesis, neurogenesis, and neurite remodeling in rats. Similarly, human MSC-Exo treatment of stroke increases long-term neuroprotection, promotes neuro-regeneration, enhances neurological recovery, and modulates peripheral poststroke immune responses but does not affect cerebral immune cell infiltration in mice. MSC-Exos significantly improve functional outcome and reduce structural injury and show promise in treating global hypoxic–ischemic injury of the fetal brain. Human MSC-Exo treatment dose dependently reduces brain neuroinflammation after traumatic brain injury in mice and significantly ameliorates inflammation induced neuronal cellular degeneration, reduces microgliosis, prevents reactive astrogliosis, and improves functional recovery in traumatic brain injury animals” (See page 1085, MSC-Exosome for Treatment of Stroke).
“MSC-Exo can be enriched with specific miRs to enhance recovery of injured tissues MSCs release functional small RNAs via their exosomes” (see right side page 1086)
“Thus, in vivo and in vitro data suggest that modulating miR content of exosome may be an effective means to amplify the therapeutic effects of exosomes for the treatment of stroke and neurological injury, as well as degenerative diseases” (see first para. page 1087).
Therefore it would have been obvious to those having ordinary skill in the art and before the effective filing date to condition the media of the MSCs with either a hypoxic environment, with TNFa or PEG2 in order to increase the ratio of M2-macrophages for creating an anti-inflammatory phenotype for neuroprotection as discussed by Maldonado-Lasunción, for the neuroprotective composition taught by Sinden and Sgambato because this process would bring about the beneficial M2 environment known for assisting with neuroprotection as just discussed.
It would have also been obvious to optimize the composition to be within the instantly claimed amount because Chen teaches wherein human MSC-exosome treatment dose-dependently reduces brain neuroinflammation significantly ameliorates inflammation induced neuronal cellular degeneration, reduces microgliosis, prevents reactive astrogliosis, and improves functional recovery in traumatic brain injury animals. Thus, finding the amount would have been an optimization well within the purview of any skilled artisan given the prior art, especially since these are the active components which give the specific activity.
It would have also been obvious to create the instant composition for promoting neurogenesis and/or immunomodulation comprising isolated exosomes from HMSCs with a carrier that is a hydrogel comprising a plurality of biocompatible polymers or oligomers cross-linked with a hydrolysable linker comprising an acrylate or methacrylate because Sgambato teaches that alginates are used for various biomedical applications, such as drug delivery and cell encapsulation, and that it is able to gel under mild conditions by the addition of divalent cations, it is biodegradable, and has low toxicity. Thus, its selection would have been obvious for the just explained reasons.
Furthermore, it would have been obvious to use methacrylates because Sgambato teaches the use of methacrylates can be photopolymerized, affording controlled hydrogel architectures.
Claim 65 is rejected under 35 U.S.C. 103 as being unpatentable over John Sinden et. al. (US20150079046A1), Sgambato et. al., Maldonado-Lasunción et. al., and Jieli Chen as applied to claims 1, 29-32, 35-37 and 40-42 above, and further in view of Yang et. al. (Detection of MMP activity in living cells by a genetically encoded surface-displayed FRET sensor, Biochimica et Biophysica Acta 1773 (2007) 400-407).
The previously combined art teaches the instant invention however are silent on the having the cell surface binding factor comprise a hybrid peptide containing an MMP2 enzyme recognizable domain being IPVSLRSG followed by DGEA exosome binding domain being that of IPVSLRSGDGEA.
Yang’s general disclosure is detecting MMP activity in living cells through genetically encoded FRET sensors (see abstract).
Yang teaches the MMP substrate site is IPVS/LRSG (the cleavage site is indicated by a slash [15]) (see Figure 1). Yang teaches that IPVS-LRSG peptide is cleaved at greatest rate by MMP-2 (see 3.1).
Although Yang does not teach the recognizable domain being followed by DGEA, a person having skill in the art would recognize that the MMP substrate site which is described IPVS/LRSG containing the cleavage sites can be used as a linker to DGEA which has previously been described as a small adhesive peptidic sequences for uses in hydrogels. Additionally, Yang also describes where in the sequence the cleavage site is located (see Figure 1) and this sequence is within the sequence being claimed, thus it would be expected that the cleavage location of the instantly claimed IPVSLRSGAGPEG (SEQ ID NO: 3) to be the same as the location described by Yang.
Therefore, it would have been obvious before the effective filing date to persons skilled in the art to use the known amino acid IPVSLRSGAGPEG (SEQ ID NO: 3) which includes the MMP substrate and known cleavage sites followed by the DGEA adhesive peptidic domain because Sgambato teaches that the DGEA is a peptide known for cell adhesion and Yang teaches that the LEGGIPVSLRPV sequence containing the IPVSLRPV sequence is a cleavable linker. Thus, combining them for the use in therapeutic purposes as a linker for targeting cells in the extracellular matrix would have been obvious.
Response to Arguments
Applicant's arguments filed 11/12/2025 have been fully considered but they are not persuasive. The applicant’s main argument is directed to the art, specifically Sinden for not teaching human mesenchymal stem cells. This however is not the case. In both rejections the Office points to Sinden’s teaching of using mesenchymal stem cells: “These conditionally immortalized stem cells are typically neural stem cells, but may be a stem cell of any type, for example a haematopoietic stem cell or a mesenchymal stem cell” (see Sinden 0205).
The applicant argues that the Office does not articulate a reason to combine the art particularly Sinden and Sgambato. This is also not the case. The Office explained that persons having skill in the art would recognize that Sgambato’s teachings that alginates are useful for various biomedical applications, such as drug delivery and cell encapsulation, and that it is able to gel under mild conditions by the addition of divalent cations, it is biodegradable, and has low toxicity. These are all reasons for utilizing hydrogels comprising polymers and hydrolysable linkers that are acrylates or methylacrylates. Sgambato teaches that usually PEG acrylates or methacrylates can be photopolymerized, affording controlled hydrogel architectures” (see page 2, 2.2). Thus persons could control the hydrogels for uses in controlled released drug compositions etc. In fact, synthetic hydrogels can be designed using polymers with controlled molecular weight and biodegradable linkers. These features allow for the fine tuning of hydrogel composition, formation dynamics, mechanical properties, and degradation rates.
The applicant argues that when Maldonado-Lasuncion and Chen are relied upon there is still no reason to “bridge the gap” between Sinden and Sgambato. The reasons to combine Sinden and Sgambato was just articulated. Sinden not only teaches neural stem-cell derived microparticles but teaches mesenchymal stem cells as can be apricated from the above rejection.
Conclusion
No claims are 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.
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JACOB A BOECKELMAN Examiner, Art Unit 1655
/ANAND U DESAI/ Supervisory Patent Examiner, Art Unit 1655