DETAILED ACTION
Examiner acknowledges receipt of the reply filed 12/30/2025, in response to the non-final office action mailed 10/1/2025.
Claims 1-4, 9, 10, 13-15, 17, 21, 23, 45, and 47-53 are pending. Claims 16, 20, 27, 42, and 46 have been cancelled. Claims 49-53 are newly added. Claim 23 is withdrawn from further prosecution for the reasons made of record.
Claims 1-4, 9, 10, 13-15, 17, 21, 45, and 47-53 are being examined on the merits in this office 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 .
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Claim Rejections - 35 USC § 112- withdrawn
The rejection of claims 1-4, 13-17, 20, 21, and 46-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of the amendment filed 12/30/2025.
Claim Rejections - 35 USC § 102- withdrawn
The rejection of claims 1, 2, 4, and 21 under 35 U.S.C. 102(a)(1) as being anticipated by He et al (Acta Biomaterialia 7:1084-1093 (2011)), is withdrawn in view of the amendment filed 12/30/2025.
Claim Rejections - 35 USC § 103- withdrawn
The rejection of claims 1-4, 9, 10, 13, 14, 16, 17, 20, 21, 45, 47 and 48 under 35 U.S.C. 103 as being unpatentable over Addison et al (U.S. 2014/0079805), and further in view of Eveleth et al (WO 2017172525- cited in IDS filed 7/5/2022) and Gajendiran et al (Tissue Engineering Part B 24:66-74 (2018)), as evidenced by N-Acetylhomocysteine thiolactone (Pubchem CID 488182000, accessed 9/26/2025 at URL pubchem.ncbi.nlm.nih.gov/substance/488182000, 5 pages- hereinafter referred to as “Pubchem”) is withdrawn.
The rejection of claims 1-4, 9, 10, 13, 14-17, 20, 21, and 45-48 under 35 U.S.C. 103 as being unpatentable over Addison et al (U.S. 2014/0079805), Eveleth et al (WO 2017172525- cited in IDS filed 7/5/2022) Gajendiran et al (Tissue Engineering Part B 24:66-74 (2018)), as evidenced by N-Acetylhomocysteine thiolactone (Pubchem CID 488182000, accessed 9/26/2025 at URL pubchem.ncbi.nlm.nih.gov/substance/488182000, 5 pages- hereinafter referred to as “Pubchem”), as applied to claims 1-4, 9, 10, 13, 14, 16, 17, 20, 21, 45, 47 and 48 above, and further in view of Westrin (U.S. 2010178320), is withdrawn.
Response to Arguments
Applicant's amendment and arguments, filed 12/30/2025 with respect to the above rejections have been fully considered and are persuasive. The rejections have been withdrawn.
Applicant's arguments filed 12/30/2025 have been fully considered but they are not persuasive with respect to the maintained objections and rejections.
Upon further consideration, a new ground(s) of rejection is made in view of the amendment filed 12/30/2025. An action on the merits is set forth herein.
Examiner Comment
Instant claims 1 and 50 are composition claims.
Claim 1 was amended to recite “the thiolated biopolymer being thiolated by reaction of a thiolactone with a primary amine group of a biopolymer, the thiolactone being a 3- to 12-membered ring comprising 2 to 10 carbons”.
New claim 50 recites “thiolated oxidized cellulose thiolated by reaction of a thiolactone with a primary amine group of oxidized cellulose, the thiolactone being a 3- to 12-membered ring comprising 2 to 10 carbons”.
The claims recite product-by-process limitations.
Maintained Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Klaxon is today Wednesday or Thursday
Claim(s) 1, 3, 21, and 48 remain/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Claude et al (WO 2006/113407- previously cited). The rejection is maintained from the office action mailed 10/01/2025, but has been amended to reflect claims filed 12/30/2025.
Claude et al teach bioscaffoldings formed of hydrogels comprising thiolated collagen [reads on thiolated biopolymer] conjugated to growth factors, e.g. VEGF, bFGF (e.g., paras. [0008], [0054]-[0055], Figs 5i-5j). The thiolated collagen and growth factor are conjugated via a disulfide bond [reads on a disulfide linkage]. Id. See Figs 5i-5j. The biofunctionality (e.g., VEGF, bFGF) is first modified with a linkage that is hydrolytically or enzymatically cleavable to form the release of the biofunctionality once the bioscaffolding has been formed in the infarcted region of the heart (e.g., paras. [0046], [0054]-[0055]). As noted in the specification, the wound environment is acidic (as-filed specification at e.g., paras. [0023], [0046]-[0047]). Claude et al do not specifically teach cleavage of the growth factors from the thiolated collagen “upon exposure to an acidic wound environment”. However, this is an inherent property of the claimed thiolated biopolymer.
MPEP § 2112.01 recites, "Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” See In re Spada (citations omitted). The claimed composition appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
As noted above, claim 1 recites a product-by-process limitation, “reaction of a thiolactone with a primary amine group of a biopolymer, the thiolactone being a 3- to 12-membered ring comprising 2 to 10 carbons”.
MPEP § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.” “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
The use of 35 U.S.C. §§ 102 and 103 rejections for product-by-process claims has been approved by the courts. “[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference. In this case, Claude et al teach bioscaffoldings/biomaterials formed of hydrogels comprising thiolated collagen [reads on thiolated biopolymer] conjugated [disulfide bridge linkage] to growth factors, e.g. VEGF, bFGF. The limitations of claim 1 are deemed to be anticipated by Claude et al. Examiner notes that a pH of the wound is an inherent property of the wound environment.
Accordingly, the limitations of claims 1, 3, 21, and 48 are satisfied. Claims 3, 21, and 48 do not further limit the structure of the claimed biopolymer.
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
Response to arguments
Applicant traversed the rejection at p. 9 of the reply filed 12/30/2025. Applicant asserts that Claude does not disclose that collagen may be “thiolated by reaction of a thiolactone with a primary amin group of a biopolymer”.
Examiner has reviewed and considered applicants arguments, but is not persuaded.
As noted in the above rejection, the recited limitation is a product-by-process limitation.
Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP § 2113. Claude et al teach the recited structure of the claimed biomaterial and thus anticipates the instant claims.
Claim(s) 1, 3, 17, 21, and 48 remain/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eveleth et al (WO 2017172525- previously cited). The rejection is maintained from the office action mailed 10/01/2025, but has been amended to reflect claims filed 12/30/2025.
Eveleth et al teach a biological matrix comprising a thiol-modified collagen conjugated to fibroblast growth factor via disulfide bonds; e.g., at para [0004], the biological matrix is modified to create thiol functional groups capable of forming disulfide bonds with the modified FGF; the biological matrix comprises at least one of thiol-modified collagen and thiol-modified hyaluronic acid (see also, e.g., paras. [0003]-[0021], [0176], [0193], claims 92, 96, 97). The compositions can include additional growth factors including but not limited to epidermal growth factor (EGF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), transforming growth factor alpha and beta (TGF-alpha and TFG-beta), platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), tumor necrosis factor alpha (T F-alpha), hepatocyte growth factor (HGF), insulin like growth factor (IGF), erythropoietin, colony stimulating factor (CSF), macrophage-CSF (M-CSF), and granulocyte/macrophage CSF (GM-CSF) (para. [0192]). Eveleth et al teach that the biological matrix can be applied to a wound for treatment thereby releasing the FGF (e.g., paras. [0015], [0058], [0148]-[0149], [0178], [0194]).
As noted in the specification, the wound environment is acidic (as-filed specification at e.g., paras. [0023], [0046]-[0047]). Eveleth et al do not specifically teach cleavage of the growth factors from the thiolated collagen “upon exposure to an acidic wound environment”. However, this is an inherent property of the claimed thiolated biopolymer.
MPEP § 2112.01 recites, "Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” See In re Spada (citations omitted). The claimed composition appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
As noted above, claim 1 recites a product-by-process limitation, “reaction of a thiolactone with a primary amine group of a biopolymer, the thiolactone being a 3- to 12-membered ring comprising 2 to 10 carbons”.
MPEP § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.” “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
The use of 35 U.S.C. §§ 102 and 103 rejections for product-by-process claims has been approved by the courts. “[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference. In this case, Eveleth et al teach a biological matrix comprising a thiol-modified collagen [reads on thiolated biopolymer] conjugated to fibroblast growth factor (FGF) via disulfide bonds [reads on a disulfide linkage]. The limitations of claim 1 are deemed to be anticipated by Eveleth et al. Examiner notes that the pH of a wound is an inherent property of the wound environment.
Accordingly, the limitations of claims 1, 3, 21, and 48 are satisfied. Claims 3, 21, and 48 do not further limit the structure of the claimed biomaterial.
Regarding claim 17, compositions can further include antioxidants or antibiotics (e.g., para. [0152], [0183]).
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
Response to arguments
Applicant traversed the rejection at p. 9 of the reply filed 12/30/2025. Applicant asserts that Eveleth does not disclose that the thiol-modified collagen may be “thiolated by reaction of a thiolactone with a primary amin group of a biopolymer, ”.
Examiner has reviewed and considered applicants arguments, but is not persuaded.
As noted in the above rejection, the recited limitation is a product-by-process limitation.
Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP § 2113. Eveleth et al teach the recited structure of the claimed biomaterial and thus anticipates the instant claims.
New Rejections
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.
Claims 1-4, 9, 10, 13-15, 17, 21, 45, and 47-49 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. This is a new rejection necessitated by the amendment filed 12/30/2025.
The amendment filed 9/22/2025 constitutes new matter.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 1 is drawn to a biomaterial comprising- a thiolated biopolymer comprising thiolated collagen, thiolated cellulose, or a combination thereof, the thiolated biopolymer being thiolated by reaction of a thiolactone with a primary amine group of a biopolymer, the thiolactone being a 3- to 12-membered ring comprising 2 to 10 carbons ;and one or more agents comprising growth factors, peptides, or combinations thereof, the peptides comprising defensins, histatins, cathelicidin LL-37, or a combination thereof; .. wherein the biomaterial is formulated such that the one or more agents undergo cleavage from the thiolated biopolymer upon exposure to an acidic wound environment having a pH of less than 7 to release the one or more agents into the wound.
Assessment of whether species are disclosed in the original specification
Examiner first notes that that the written description inquiry is limited to that which is contained within the four corners of the specification, not the extent to which the skilled artisan, given his or her knowledge of the art, would have considered it to expand with only routine experimentation. See AriadPharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010); see also id. at 1352 (“[I]t is the specification itself that must demonstrate possession. . . . a description that merely renders the invention obvious does not satisfy the requirement.").
The specification does not explicitly or implicitly teach “formulated such that the one or more agents undergo cleavage”. The term “formulated” is not recited anywhere in the specification.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the genus encompassed by the instant claims constitutes new matter. The claim limitation of a “formulated such that the one or more agents undergo cleavage” was not expressly or implicitly taught in the specification.
Accordingly, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claims 50-53 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. This is a new rejection necessitated by the amendment filed 12/30/2025.
The amendment filed 9/22/2025 constitutes new matter.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 50 is drawn to a biomaterial comprising; thiolated oxidized cellulose thiolated by reaction of a thiolactone with a primary amine group of an oxidized cellulose, the thiolactone being a 3- to 12- membered ring comprising 2 to 10 carbons; and one or more agents comprising growth factors, peptides, or combinations thereof, the peptides comprising defensins, histatins, cathelicidin LL-37, or a combination thereof; …, and wherein the biomaterial is formulated such that the one or more agents undergo cleavage from the thiolated oxidized cellulose upon exposure to an acidic wound environment having a pH of less than 7 to release the one or more agents into the wound.
Assessment of whether species are disclosed in the original specification
Examiner first notes that that the written description inquiry is limited to that which is contained within the four corners of the specification, not the extent to which the skilled artisan, given his or her knowledge of the art, would have considered it to expand with only routine experimentation. See AriadPharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010); see also id. at 1352 (“[I]t is the specification itself that must demonstrate possession. . . . a description that merely renders the invention obvious does not satisfy the requirement.").
The specification does not explicitly or implicitly teach “formulated such that the one or more agents undergo cleavage”. The term “formulated” is not recited anywhere in the specification.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the genus encompassed by the instant claims constitutes new matter. The claim limitation of a “formulated such that the one or more agents undergo cleavage” was not expressly or implicitly taught in the specification.
Accordingly, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed 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.
Claims 3, 4, 9, 10, 13-15, 45, and 48 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. This is a new rejection necessitated by the amendment filed 12/30/2025.
Claim 2 recites the limitation "the form". There is insufficient antecedent basis for this limitation in the claim.
The metes and bounds of claim 3 are deemed to be indefinite. It is unclear as to what is the intended claim scope for claim 3, specifically as relating to further reciting claim 2.
Claim 3 recites: The biomaterial of claim 1, wherein the thiolated biopolymer is thiolated by reaction of a thiolactone with a primary amine group of a biopolymer, wherein the thiolactone is a 3- to 12-membered ring comprising 2 to 10 carbons claim 2, wherein the thiolactone is a 3- to 8-membered ring having 2 to 5 carbon atoms. It is unclear as to what is the intended claim scope for claim 3.
Because claims 4, 9, 10, 13-15, 45, and 48 depend from indefinite claim 3 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
The metes and bounds of claim 21 are deemed to be indefinite. It is unclear as to what is the intended claim scope for claim 21, specifically as relating to further reciting claim 3.
Claim 21 recites: The biomaterial of claim 1, wherein the one or more agents undergo cleavage from the thiolated biopolymer upon exposure to an acidic wound environment to release the one or more agents into a wound, and wherein the biomaterial is configured to be administered directly to a wound claim 3, wherein the one or more agents are configured to undergo cleavage from the thiolated biopolymer when exposed to an acidic wound environment having a pH of less than 5.
Examiner further cautions Applicant about multiple dependent claim language, e.g., claim depending from claim 3. Claim 3 is construed as depending from both claims 1 and 2.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-4, 9, 10, 13,14, 17, 21, 45, and 47-52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Addison et al (U.S. 2014/0079805- previously cited), and further in view of Eveleth et al (WO 2017172525- previously cited), Gajendiran et al (Tissue Engineering Part B 24:66-74 (2018)- previously cited) and Poole (Free Radical Biology and Medicine 80:148–157 (2015)). This is a new rejection necessitated by the amendment filed 12/30/2025.
Addison et al teach biomaterials comprising a polymeric substrate (collagen and/or oxidized regenerated cellulose) complexed to silver (Ag+) (e.g., abstract, paras. [0027]-[0032], Ex 1). “Bioabsorbable polymer” refers to a polymer that is fully degraded and absorbed in vivo in the mammalian body (para. [0017]). Bioabsorbable polymers include collagens, bioabsorbable cellulose derivatives such as oxidized celluloses, and mixtures thereof (para. [0019]). In particular embodiments, the polymeric substrate comprises (and may consist essentially of) a mixture of: (a) collagen and/or chitosan; and (b) oxidized regenerated cellulose (OCR)(e.g., para [0029]). The biopolymers can further include growth factors (e.g. fibroblast growth factor or platelet derived growth factor) (e.g., para. [0049]). The biomaterials can be applied to a wound for treatment (e.g., abstract, paras. [0017], [0019]-[0029], [0057]-[0058], claim 1).
Addison et al. do not expressly teach that the biopolymer is thiolated, or that the one or more agents (e.g., growth factor) is conjugated to the thiolated biopolymer via a disulfide bond.
Eveleth et al teach a biological matrix comprising a thiol-modified collagen conjugated to fibroblast growth factor via disulfide bonds; e.g., at para [0004], the biological matrix is modified to create thiol functional groups capable of forming disulfide bonds with the modified FGF; the biological matrix comprises at least one of thiol-modified collagen and thiol-modified hyaluronic acid (see also, e.g., paras. [0003]-[0021], [0176], [0193], claims 92, 96, 97). The compositions can include additional growth factors including but not limited to epidermal growth factor (EGF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), transforming growth factor alpha and beta (TGF-alpha and TFG-beta), platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), tumor necrosis factor alpha (T F-alpha), hepatocyte growth factor (HGF), insulin like growth factor (IGF), erythropoietin, colony stimulating factor (CSF), macrophage-CSF (M-CSF), and granulocyte/macrophage CSF (GM-CSF) (para. [0192]). Eveleth et al teach that the biological matrix can be applied to a wound for treatment thereby releasing the FGF (e.g., paras. [0015], [0058], [0148]-[0149], [0178], [0194]).
Gajendiran et al is a review article discussing developments in the preparation and fabrication of thiolated polymers (abstract). Thiolated polymers are synthesized by several approaches using various thiolation reagents. Chemical reagents, such as L-cysteine (L-CYS), cysteamine (CYS), thioglycolic acid (TGA), and thiolactone-based reagents are used widely for the preparation of thiolated polymers (p. 67). Thiolactones, such as N-acetyl homocysteine thiolactone and 4-butyro thiolactone, are highly reactive toward the amine group, and were attached effectively to the amine group of the polymers (pp. 67 and 69). Table 1 teaches specific thiolating reagents that have been successfully used in synthesizing thiolated polymers (p. 68).
Poole is a review article regarding thiols and cysteines in biology and chemistry. Cysteine is one of the least abundant amino acids, yet it is frequently found as a highly conserved residue within functional (regulatory, catalytic, or binding) sites in proteins (abstract). The thiol (or “sulfhydryl”) group of cysteine [Cys side chain] is ionizable, with a negatively charged thiolate group being generated after deprotonation, boosting its reactivity (e.g., p. 148, Fig 1). The thiol or thiolate group of cysteine imparts functional sites their specialized properties (e.g., nucleophilicity, high-affinity metal binding, and/or ability to form disulfide bonds). Id. The sulfhydryl/thiol group of a cysteine side chain within a growth factor can form a disulfide bond with a sulfhydryl group of a thiolated polymer, e.g., collagen and/or cellulose.
It would have been obvious to one of ordinary skill in the art to have prepared a biopolymer comprising a thiolated biopolymer and one or more agents comprising growth factors, wherein the one or more agents are conjugated to the thiolated biopolymer via a disulfide bond. The skilled artisan would have known that Addison et al. taught biomaterials comprising a bioabsorbable polymer (e.g., collagens, bioabsorbable cellulose derivatives, e.g., oxidized regenerated cellulose (OCR), and mixtures thereof), complexed with silver, can further include growth factors. Addison et al. taught methods of preparation, and that the biomaterials could be used in wound care. Eveleth et al also taught a biological matrix for wound care comprising a thiol-modified collagen conjugated to fibroblast growth factor (FGF) via disulfide bonds. Eveleth et al further taught inclusion of additional growth factors in the biological matrix. The skilled artisan would have had a reasonable expectation of success in preparing a claimed thiolated biomaterial because Gajendiran et al taught thiolating reagents and methods of preparing thiolated biopolymers, e.g., thiolated-collagen, thiolated-OCR, or a mixture thereof.
The U.S. Federal Circuit has explicitly stated that in order to make a prima facie case of obviousness, the suggestion and motivation to combine the references need not be explicitly stated in the text of the references. In DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641 (Fed. Cir. 2006), the Court writes, “the suggestion test is not a rigid categorical rule. The motivation need not be found in the references sought to be combined, but may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself. In re Dembiczak, 175 F.3d 994, 999 [50 USPQ2d 1614] (Fed. Cir. 1999). As we explained in Motorola, Inc. v. Interdigital Tech. Corp., 121 F.3d 1461, 1472 [43 USPQ2d 1481] (Fed. Cir. 1997), ‘there is no requirement that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.’” See Dystar at 1645. “Our suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense.” In this case, the prior art taught biomaterials comprising a bioabsorbable biopolymer (collagen, OCR, mixture thereof), growth factors conjugated to biopolymers via disulfide bonds, thiolating reagents and methods of preparing the thiolated biopolymers. Thus, the motivation to combine the references can be found in the common knowledge of the art and common sense of its skilled practitioners.
Additionally, it would have been obvious to one of ordinary skill in the art to combine the teachings of Addison et al. and Eveleth et al because both taught biomaterials for wound care comprising the claimed biopolymers and growth factors conjugated via a disulfide bond. One of ordinary skill in the art would be motivated to combine the references because Eveth et al taught that disulfide bonds stabilized the biomaterial. Gajendiran et al taught additional thiolating reagents for preparing thiolated biopolymers, e.g., thiolated-collagen, thiolated-OCR, or a mixture thereof. One of ordinary skill in the art would be motivated to try with a reasonable expectation of success. It has been held that under KSR that “obvious to try” may be an appropriate test under 103. The Supreme Court stated in KSR, When there is motivation “to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.” KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727,_,82 USPQ2d 1385, 1397 (2007).
The “problem” facing those in the art was availability of thiolated biopolymers. Gajendiran et al taught specific thiolating reagents and methods of preparing thiolated biopolymers (e.g., Table 1). Table 1 teach a finite number of thiolating reagents that were successfully used in preparation of thiolated biopolymers. See also Gajendiran et al generally for disclosure of preparations and specific examples of thiolated biopolymers. The skilled artisan would have had reason to try these thiolating reagents with the reasonable expectation that at least one thiolating reagent would be successful in preparing the claimed thiolated biopolymer. Preparing a thiolated biopolymer (collagen, OCR, or combination thereof) by reaction with a thiolactone (e.g., N-acetyl homocysteine) with the primary amine group of a biopolymer, is a “product not of innovation but of ordinary skill and common sense,” leading to the conclusion that invention is not patentable as it would have been obvious. The skilled artisan would have recognized from Poole that a cysteine sulfhydryl group (Cys side chain) within a growth factor can form a disulfide bond with a thiolated biopolymer taught by the method of Gajendiran et al.
Claims 1 and 50 recite a product-by-process limitation, “reaction of a thiolactone with a primary amine group of a biopolymer, the thiolactone being a 3- to 12-membered ring comprising 2 to 10 carbons”.
MPEP § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.” “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
The use of 35 U.S.C. §§ 102 and 103 rejections for product-by-process claims has been approved by the courts. “[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
As noted in the specification, the wound environment is acidic (as-filed specification at e.g., paras. [0023], [0046]-[0047]). The cited references do not specifically teach cleavage of the growth factors from the thiolated collagen “upon exposure to an acidic wound environment”. However, this is an inherent property of the claimed thiolated biopolymer. Examiner notes that a pH of a wound is an inherent property of the wound environment.
Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference.
Accordingly, claims 1, 4, and 50 are rendered obvious. Examiner notes that claim 50 recites comprising language. Thus, a biomaterial comprising a thiolated OCR and thiolated collagen reads on claim 50.
Regarding claim 2, Addison et al teach that the polymeric substrate may make up at least 50% by weight of the wound dressing material (para. [0016]). Example 1 discloses an antioxidant and antimicrobial wound dressing material comprising collagen/ORC freeze-dried sponge [reads on configured to be administered directly to a wound]. See also e.g., paras. [0014], [0028]. Regarding claims 3 and 48, Gajendiran et al teach N-acetyl homocysteine thiolactone is a thiolating reagent that reacts with a primary amine group of the biopolymer (pp. 67-69). It is noted that claims 3 and 48 do not further limit the structure of the claimed biomaterial.
Regarding claim 9, Addison et al teach that the polymeric substrate may make up at least 50% by weight of the wound dressing material and is not water soluble (para. [0016]). Addison et al teach that collagen can be in the form of fibrous collagen (e.g., para [0027]). It would have been obvious to one skilled in the art at the time of the filing of the specification to further optimize the amount of collagen as such optimization was routinely done in the art. MPEP §2144.05 (II). As noted in the as-filed specification at para. [0016], collagen with a weight-average molecular weight of 5,000 has a weight-average molar mass of 5,000 g/mol. Accordingly, claim 9 is rendered obvious. Regarding claims 10 and 51, the oxidized cellulose has an average molecular weight greater than 50,000 (e.g., paras. [0022]-[0025]). The polymeric substrate may make up at least 50% by weight of the wound dressing material, for example at least 75% by weight or at least 90% by weight (para. [0016]). Regarding claims 13, 14, and 52, Addison et al teach that the biomaterials may comprise 0-10% by weight, preferably 0-5% by weight of one or more additional therapeutic wound healing agents, such as growth factors (e.g. fibroblast growth factor [FGF] or platelet derived growth factor [PDGF] (e.g., para. [0049]). Eveleth et al and Poole teach that the thiolated biopolymer can form a disulfide bond with another thiol functionality, e.g., cysteine amino acid side chain of the one or more agents (growth factor or peptide). Regarding claims 17, the biomaterial may further comprise antibiotics (e.g. penicillins or streptomycins), antiseptics (e.g. chlorhexidine), or antioxidant (e.g., paras. [0044]-[0049], [0055], Ex 1). Eveleth et al teach inclusion of antioxidants or antibiotics (e.g., para. [0152], [0183]).
Regarding claim 21, Addison et al teach that the biomaterial is administered to a wound and is fully degraded and absorbed in vivo in the mammalian body (e.g., paras. [0017], [0019]-[0029], [0057]-[0058], Ex 7). Oxidized cellulose is biodegradable and bioabsorbable under physiological conditions (para. [0021]). The pH of the wound in an inherent property of a wound environment. Accordingly, claim 21 is rendered obvious. Regarding claim 45, Addison et al teach that the polymeric substrate comprises a mixture of collagen and oxidized regenerated cellulose (e.g., paras.[009]-[0011], [0028]-[0032], Example 1). The polymeric substrate comprises (and may consist essentially of) a mixture of: (a) collagen and/or chitosan; and (b) oxidized regenerated cellulose, for example in a dry weight ratio range of from about 90:10 to about 10:90 of collagen/chitosan:ORC, preferably from about 75:25 to about 25:75, and particularly from about 60:40 to about 40:60.Eveleth et al further teach conjugation of FGF to a thiolated polymer (e.g., para [0029]). It would have been obvious to one skilled in the art at the time of the filing of the specification to further optimize the weight ratio of thiolated collagen to thiolated OCR as such optimization was routinely done in the art. MPEP §2144.05 (II). Regarding claim 47, Addison et al teach that collagen is complexed with silver (e.g., paras. [0032]-[0041], Ex 1). Regarding claim 49, Addison et al disclose collagen/ORC freeze-dried sponge material that can be administered to a wound (e.g., Example 1). The material will absorb water or wound fluid and hence become wet, swell or become a gelatinous mass but will not spontaneously dissolve or disperse therein. Low solubility renders such materials especially suitable for use as wound dressings to remove reactive oxygen species from the wound fluid (para [0054]).
Claims 1-4, 9, 10, 13,14, 17, 21, 45, and 47-52 are obvious in view of the teachings of the cited references.
Response to arguments- as relating to previous 103 rejection of Addison, Eveleth, Gajendiran, and Pubchem (withdrawn herein)
Applicant traversed the rejection at pp. 9-13 of the reply filed 12/30/2025. Applicant asserts that Addison does not disclose or suggest that the wound dressing material may be formulated such that one or more agents undergo cleavage from the polymeric substrate (reply at p. 10). Applicant asserts that Eveleth does not disclose that a thiol-modified collagen in the thiolated by reaction of a thiolactone with a primary amine group of the biopolymer, or that the growth factor undergoes cleavage upon exposure to an acidic wound environment. Id. Applicant asserts Gajendiran does not disclose or suggest that thiolated polymers are synthesized using the dilating reagents can be conjugated to one or more agents comprising growth factors, peptides, or combinations thereof (reply at pp. 10-11). Applicant asserts Gajendiran is limited to teaching formation of disulfide bonds between polymer chains, not between thiolated collagen and one or more of recited agents (p. 11). Applicant asserts that the skilled artisan would not have understood that thiolated collagen synthesized using the reagents described in Gajendiran could be used to modify the biological matrices described in Eveleth to create thiol functional groups capable of forming disulfide bonds with the modified FGFs in Eveleth. Applicant alleges hindsight analysis by the Examiner (reply at p. 11).
Examiner has reviewed and considered applicants arguments, but is not persuaded.
As noted in the rejection, product by process limitations do not limit the structure of the claimed biomaterial.
Contrary to applicant’s assertions, examiner is not asserting that thiolated collagen synthesized using the thiolating reagents described in Gajendiran could be used to modify the biological matrices described in Eveleth to create thiol functional groups capable of forming disulfide bonds with the modified FGFs described in Eveleth (reply at p. 11). Gajendiran is cited for the purpose of establishing that thiolated biopolymers and methods of preparing or known in the prior art. Poole establishes that sulfhydryl groups (e.g., cysteine side chain and thiol groups of thiolated biopolymers) can form disulfide bonds.
Please refer to the entirety of the 103 rejection set forth herein for full analysis.
Claim(s) 1-4, 9, 10, 13-15, 17, 21, 45, and 47-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Addison et al (U.S. 2014/0079805- previously cited), and further in view of Eveleth et al (WO 2017172525- previously cited), Gajendiran et al (Tissue Engineering Part B 24:66-74 (2018)- previously cited) and Poole (Free Radical Biology and Medicine 80:148–157 (2015), as applied to claims 1-4, 9, 10, 13, 14, 17, 21, 45, and 47-52 above, and further in view of Westrin (U.S. 2010178320- previously cited).
The teachings of Addison et al, Eveleth et al, Gajendiran et al and Poole are set forth above. Although Addison et al and Eveleth et al teach that the biomaterials for wound care can further include antibiotics/antibacterial agents, the references do not explicitly teach defensin, histatin, or cathelicidin LL-37 (e.g., Addison et al at para. [0152], [0183]; Eveleth et al at e.g., para. [0049]).
Westrin teach a wound care product comprising a wound care material and a polypeptide having wound care properties (abstract). Wound care materials include alginates, collagen based materials, oxidized regenerated cellulose and mixtures thereof (para. [0031], claim 96). Polypeptides having wound care properties include cathelicidin, such as LL-37 (abstract, paras. [0048]-[0052]). LL-37 can enhance epithelial regeneration and/or healing of wound epithelia and/or wound stroma (e.g., paras. [0057], claims 93, 105). Additional antimicrobial polypeptides include defensins, gramicidin S, magainin, cecropin, histatin, hyphancin, cinnamycin, burforin 1, parasin 1 and protamines (para. [0104]).
It would have been obvious to one of ordinary skill in the art to further conjugate via a disulfide bond a peptide comprising cathelicidin (e.g., LL-30), defensins, or histatin in the thiolated biopolymers of taught by the combination of Addison et al, Eveleth et al, and Gajendiran et al because the references all explicitly taught biopolymers for use in wound care comprising antibacterial agents. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See M.P.E.P. § 2144.06. The skilled artisan would have had a reasonable expectation of success because the cited references taught methods of preparing the thiolated biomaterials. As taught by Eveleth and Poole, a sulfhydryl group of a cysteine within a cathelicidin (e.g., LL-30), defensins, or histatin can form a disulfide bond with a thiol-modified collagen or a thiol-modified cellulose.
Accordingly, claims 15 and 53 are rendered obvious. See above regarding product-by-process claim limitations.
Claims 1-4, 9, 10, 13-15, 17, 21, 45, and 47-53 are obvious in view of the teachings of the cited references.
Response to arguments- as relating to previous 103 rejection of Addison, Eveleth, Gajendiran, Pubchem, and Westrin (withdrawn herein)
Applicant traversed the rejection at p. 13 of the reply filed 12/30/2025. Applicant asserts that Westrin does not make up for the alleged deficiencies of Addison, Eveleth, Gajendiran, and Pubchem. Applicant asserts that Westrin does not disclose that the polypeptide can be conjugated via a disulfide linkage between the biopolymer and the thiol functionality of the polypeptide, as required claim 1 (p. 13).
Examiner has reviewed applicants arguments, but is not persuaded.
Please refer to examiner’s counter-arguments under the 103 rejection above which are incorporated herein.
Relevant Art Not Relied Upon
Kang et al (Macromol Chem Phys 217:1322-1334 (2016) teach the introduction of thiol groups to cellulosic backbones can be used for the fabrication of cellulose-based gels that have biological environment stimuli-responsive properties, which can be used as carriers for drug and gene delivery. Thiolated HPC (HPCSH) and dual stimuli-sensitive nanogels (p. 1327). The formed nanogels exhibit reduction-responsive degradation in the presence of excess cellular reducing agent such as glutathione (p, 1328). Thus, thiolated cellulose biopolymers were known in the prior art.
Stemberger (U.S. 4407787- cited in IDS filed 7/5/2022) teaches a tissue-adherent collagenous dressing, comprising collagen present in combination with a resorbable biopolymer from the group consisting of fibrinogen, gelatin modified to contain reactive SH groups, collagen modified to contain reactive SH groups, and regenerated oxycellulose modified to contain reactive SH groups (claim 1). The material further includes a medicinally active agents, e.g. an antibiotic (claims 2-3). The dressing can be in the form of a sponge (claim 6). Claim 12 is drawn to a tissue-adherent collagenous dressing, comprising collagen present in combination with resorbable regenerated oxycellulose modified to contain reactive SH groups. See also example 4, disclosing the dressing containing a collagen dressing that was freeze-dried.
Harvey et al (U.S. 6309454) disclose a sterile freeze-dried sponge, wherein at least 80% by weight of the sponge consists of collagen and oxidized regenerated cellulose in the weight ratio 60:40 to 40:6 (abstract). The weight ratio of collagen to oxidized regenerated cellulose is from 50:50 to 55:45 and the pH of the aqueous dispersion is from 2.9 to 3.1 (claim 9). The sponge comprises at least 80% by weight of a mixture of collagen and ORC in the rate ratio 60:40 to 40:60. Preferably, the weight ratio contains a small excess of collagen, in a range 50:50 to 40:60 ORC:collagen. Preferably, the freeze-dried sponge consists essentially of collagen, ORC, water and up to 5% of one or more therapeutically active substances such as growth factors (col 1, l. 61- col 2, l. 4).
Schaufler (US 7098315) teaches a method of preparing a collagen sponge comprises mixing air into a collagen gel, so as to obtain a collagen foam which is dried (abstract). The collagen sponge may be used as a material for sealing wounds. Id. Collagen has been used as a hemostyptic agent since the late sixties. Collagen is the most frequent structural protein in all mammalians. Table 2 discloses 5 collagen sponges where the maximum soluble protein content was 0.11% (Sponge V) with lowest soluble protein content was 0.04% (Sponge IV).
Haynes et al (U.S. 5660857) discloses a process for preparing a composite comprising an insoluble protein matrix and an oleaginous material, which is useful as a material for surgical dressings and biomedical implant (abstract). The process comprises preparing an insoluble protein based sponge, e.g., freeze-dried insoluble fibrous collagen (claims 5, 8-10).
Dean et al (WO 86/05811) discloses a weighted microsponge for immobilizing bioactive materials, the microsponge comprising a highly cross-linked collagen matrix (abstract). The crosslinked collagen can be prepared from both soluble collagens and insoluble collagens of the Types I, II and III. The soluble collagens are prepared by limited enzymatic digestion and/or extraction of tissue enriched in such collagen types. Insoluble collagens are derived from the following typical sources: Type I collagen: bovine, porcine, chicken and fish skin, bovine and chicken tendon and bovine and chicken bones including fetal tissues; Type II collagen: bovine articular cartilage, nasal septum, sternal cartilage; and Type III collagen: bovine and human aorta and skin (pp. 7-8).
Finkenaur et al (US 5427778) teach gel formulations containing polypeptide growth factors having human mitogenic or angiogenic activity are provided. The gel formulations are useful for topical or incisional wound healing for cutaneous wounds, in the anterior chamber of the eye and other ophthalmic wound healing (abstract). The gels comprise an effective wound healing amount of a growth factor selected from the group consisting of EGF, acidic FGF, basic FGF, PDGF, TGF-alpha, TGF-beta, NGF, IGF-I, IGF-II, angiogenin, and mixtures thereof (claim 1). Gel polymer includes collagen and cellulose (cols 4-7). The topical or incisional gel may comprise 1 to 20% by weight of a cellulose derivative having a molecular weight of about 50,000 to 700,000. In a preferred embodiment, the cellulose derivative is present at 2-8% by weight and has a molecular weight in the range 80,000-240,000. Id. The gels may be used to treat wounds (col 7).
Watt et al (WO9800180) teach an oxidized cellulose, preferably oxidized regenerated cellulose (ORC), and complexes thereof with structural proteins such as collagen, for the preparation of wound dressings for the treatment of chronic wounds (abstract). The dressing is a knitted, woven or nonwoven fabric of ORC suitable for application directly to the surface of a wound as a wound dressing, or a semi-solid ointment for topical application containing dispersed ORC fibers or powder, or a collagen/ORC sponge. Id. The collagen may also comprise solubilised collagen or soluble collagen fragments having molecular weights in the range 5,000-100,000, preferably 5,000-50,000 (p. 7). The oxidized cellulose comprises water-soluble oxidized cellulose fragments having molecular weights in the range 5,000-50,000 (claims 5, 18). The collagen is fibrous, substantially insoluble collagen (claim 17). The weight ratio of protein to oxidized cellulose is from 1:99 to 99.99 (claim 12). The protein/oxidized cellulose complexes have an ability to bind to growth factors, in particular, platelet derived growth factor. Accordingly, the use of oxidized cellulose or complexes thereof with a structural protein to bind one or more cell growth factors. Preferably, the cell growth factor is platelet derived cell growth factor (PDGF), e.g., pp. 5, 8-9, claim 22. A bioabsorbable sponge for application to a chronic wound, said sponge comprising from 0.1% to 50% w/w of oxidized cellulose and from 50% to 99.9% of one or more structural proteins (e.g., p. 6, claim 24). Examples 1-4 disclose collagen/oxygen regenerated cellulose sponges. See also pp. 6-7.
Conclusion
No claims are allowed.
Claims 1-4, 9, 10, 13-15, 17, 21, 23, 45, and 47-53 are pending. Claim 23 is withdrawn.
Claims 1-4, 9, 10, 13-15, 17, 21, 45, and 47-53 are rejected.
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 KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
/JULIE HA/ Primary Examiner, Art Unit 1654