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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/5/2026 has been entered. Claims 1,20,24-37 are pending; claims 2-19,21-23 have been cancelled.
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.
Claims 1, 20, 24, 27, 30 – 37 are rejected under 35 U.S.C. 103 as being unpatentable over Becker et al. (US 2018/0028468 A1) in view of Eavey et al. (US 2005/0123520 A1) and Yadav et al. (US 2019/0015468 A1).
Re claims 1 and 35:
Becker teaches 1. A method in a non-human animal (Becker, [0049]; [0069]; [0091]; [0109]; [0098], “As used herein, "subject" refers to any mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, sheep, pigs, cows, etc.”), the method comprising:
contacting a wound in a non-human animal with a composition (Becker, [0049], “transdermal patches, dressings, pads, wraps, matrices and bandages capable of being adhered or otherwise associated with the skin of a subject, said articles being capable of contacting a wound”; [0058], “a wound scaffold, wound dressing or wound healing”; [0109], “may be dispersed in or on a solid sheet of wound contacting material”) comprising i) an electrospun scaffold (Becker, [0090]) comprising collagen and a synthetic polymer (Becker, [0222], “The scaffold may be created by electrospinning the mixture of the collagen and the polymer comprising the scaffold into fibers to create a scaffold sheet”; [0322], “, scaffold fabrication was obtained by the following method: a mixture of 95% collagen and 5% PCL was electrospun into fibers to create a sheet of scaffold”); and ii) a senescence-inducing agent (Becker, [0077], “preparing scaffolds coated with one or more polymers with anti-Cx antisense polynucleotides”; [0223], “the scaffolds were soaked in a thermo-reversible medium containing connexion 43 antisense oligodeoxynucleotides”; [0371]; [0206], “gap junction modifying agent may include or exclude, for example … doxorubicin (and other anthraquinone derivatives)”).
35. A composition in a non-human animal (Becker, [0049]; [0069]; [0091]; [0109]; [0098], “As used herein, "subject" refers to any mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, sheep, pigs, cows, etc.”), the composition comprising
a scaffold and a senescence inducing agent (Becker, [0077], “preparing scaffolds coated with one or more polymers with anti-Cx antisense polynucleotides”; [0223], “the scaffolds were soaked in a thermo-reversible medium containing connexion 43 antisense oligodeoxynucleotides”; [0371]; [0206], “gap junction modifying agent may include or exclude, for example … doxorubicin (and other anthraquinone derivatives)”), wherein the scaffold comprises an electrospun scaffold comprising collagen and a synthetic polymer (Becker, [0222], “The scaffold may be created by electrospinning the mixture of the collagen and the polymer comprising the scaffold into fibers to create a scaffold sheet”; [0322], “, scaffold fabrication was obtained by the following method: a mixture of 95% collagen and 5% PCL was electrospun into fibers to create a sheet of scaffold”).
Becker does not explicitly disclose A method for generating a wound model … generating a wound model in the non-human animal … to induce a foreign body reaction within the wound, delay wound healing. Eavey et al. (US 2005/0123520 A1) teaches methods of making living tissue constructs having a predetermined shape by obtaining a negative mold having a defined shape (Eavey, Abstract). Eavey teaches generating a wound model in the non-human animal (Eavey, [0034], “molds can be made of any materials that can be filled with a hydrogel and maintain their shape over time when implanted into a person or animal”; [0011], “obtaining a suitable negative mold having a three-dimensional negative shape of the anatomical feature”; [0013], “A "hydrogel" is a substance formed when an organic polymer (natural or synthetic) is set or solidified to create a three-dimensional open-lattice structure”; [0047], “Bioerodible or biodegradable polymers, i.e., polymers that dissolve or degrade within a period that is acceptable in the desired application (in vivo "culturing" of the mold)”; [0068], “The skin mold would be in the shape of a defect or wound in the skin that is to be repaired”). Therefore, in view of Eavey, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method/composition described in Becker, by providing the molds as taught by Eavey, since Eavey states “making living tissue constructs having a predetermined shape by obtaining a negative mold having a defined shape; suspending isolated tissue precursor cells in a hydrogel to form a liquid hydrogel-precursor cell composition; filling the liquid hydrogel-precursor cell composition into the mold; implanting the filled mold into a living host for incubation; removing the mold after a suitable incubation period; and removing the living tissue construct from the mold. The final living tissue construct can then be surgically implanted into a patient” (Eavey, Abstract).
Eavey teaches a method of creating a mold where a "hydrogel" is a substance formed when an organic polymer (natural or synthetic) is set or solidified to create a three-dimensional open-lattice structure (Eavey, [0013]). The cells are then suspended in a hydrogel, such as 2% alginate, to produce a hydrogel-cell composition … The hydrogel-cell composition can be introduced into the mold simultaneously with a curing composition (Eavey, [0035]). Yadav et al. (US 2019/0015468 A1) states: “… Some reports describe that alginate used in wound care products may cause long term foreign body type reaction” and foreign body type reaction inherently delay wound healing. Therefore, in view of Yadav, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the mold described in Eavey, by providing alginate as taught by Yadav, since alginate used in wound care products may cause long term foreign body type reaction.
Note: Regarding “Foreign body Reaction” or “FBR”, Applicant’s published application, para. [0042] and [0063] state “the composition is capable of inducing a foreign body reaction (FBR) within the wound of an animal” and para. [0005], states “a composition comprising a scaffold and a senescence-inducing agent”. Furthermore, in para. [0053] states “The senescence-inducing agent may include DNA damaging agents, reactive oxygen species generating agents, differentiation agents or ionizing radiation. The senescence-inducing agent may be a biofilm conditioned media (BCM) or a nicotinamide phosphoribosyl-transferase inhibitor. The senescence-inducing agent may also be, for example, aphidicolin, bleomycin, cisplatin, doxorubicin, etoposide, mitoxantrone, retinals, hydroxyurea, carboplatin or docetaxel. The senescence-inducing agent may also be any senescence-inducing agent disclosed in Ewald J A et al 2010 or Mikula-Pietrasik, J. et al. 2020.” (Applicant’s, [0053]). The added limitation does not explicitly define in the claim; nor explained in the specification what chemical compound(s) that requires to induce a foreign body reaction within the wound. The office can only rely on the definition of a senescence-inducing agents defined in the specifications which applicant claimed to be able to induce FBR.
Additionally, it is the examiner’s position that the ability for senescence-inducing agent to induce a foreign body reaction (FBR) varies from animal to another animal and compound to another compound. Some animals have more severe response to one type of senescence-inducing agent to another type. This limitation adds little weight to the claims.
Re claim 20:
20. The method of claim 1, wherein the wound model is a perturbed wound model (Eavey, [0027], “the hydrogelcell composition is delivered into the mold and, optionally, cured or set, or partially cured or set, to form a solid or semi-solid, three-dimensional living tissue construct”).
Re claim 24:
24. The method of claim 1, wherein comprise or consist of polycaprolactone (PCL) and collagen (Becker, [0015]; [0016]; [0222]).
Re claim 27:
27. The method of claim 1, wherein the senescence-inducing agent is biofilm conditioned media (BCM) (Becker, [0243]).
Re claim 30:
30. The method of claim 1, wherein the method comprises generating a wound in the animal prior to step (a) (Becker, [0034]).
Re claim 31:
31. The method of claim 30, wherein the wound is generated by a punch biopsy (Becker, [0016]).
Re claim 32:
32. The method of claim 1, wherein the method comprising sealing the wound (Becker, [0243]).
Re claim 33:
33. The method of claim 1, wherein the method comprises contacting the wound with the composition once a day over three days (Becker, [0240]).
Re claim 34:
34. A method of identifying a candidate therapeutic agent for treating a wound, the method comprising: a) generating a wound model in an animal according to a method of claim 1, and b) contacting the wound model with the candidate therapeutic agent (Becker, [0119]; [0390]).
Re claims 36 - 37:
36. The method of 1, wherein the wound is not healed after 10 days. 37. The method of 1, wherein the wound is not healed after 10 days in mice or after 30 days in pigs (Becker, [0087] – [0088]; figs. 18A – 18B; “FIG. 27 shows the histology of granulation tissue area at Day 15 of wound healing. Shown are the experimental setup of the image viewed, the images of stained samples of the treatment groups, and a graph showing the measured granulation tissue areas”; histology of granulation tissue area at Day 15 shows that rat granulation tissues area still healing after 15 days).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over in Becker et al. (US 2018/0028468 A1) and Eavey et al. (US 2005/0123520 A1) as applied to claim 1 above, and further in view of Dai et al. (US 2010/0062041 A1)
Re claim 25:
Becker states “… scaffold fabrication was obtained by the following method: a mixture of 95% collagen and 5% PCL was electro spun into fibers to create a sheet of scaffold” (Becker, [0322]). Becker does not explicitly disclose 25. The method of claim 1, wherein the scaffold comprises 80% w/w polycaprolactone (PCL) and 20% w/w collagen. Dai teaches an invention relates to skin substitutes suitable for use in a living subject for purpose of repairing damaged tissues (Dai, Abstract). Dai teaches 25. The method of claim 1, wherein the scaffold comprises 80% w/w polycaprolactone (PCL) and 20% w/w collagen (Dai, [0058], “a biocomposite membrane comprises PCL and at least one material selected from collagen and gelatin, in a weight ratio of 4:1 … the biocomposite membrane comprises PCL, collagen and gelatin, in which the weight ratio of collagen and PCL … is between 1:4 to 1:20, and more”; collagen – 1 (20%) and PCL – 4 (80%)). Therefore, in view of Dai, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method described in Becker, by providing the ratio of 1:4 as taught by Dai, since Dai explains that such ratio allows the biocomposite membrane to be useful as a wound dressing or living organ coverage to promote wound healing and/or tissue regeneration, in particular, for treating subjects with ear drum defect, disruption of tendon/nerve, and/or skin damage that includes bum injuries, ulcers, impaired pigmentation, excisions or other dermatological conditions (Dai, [0013]).
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over in Becker et al. (US 2018/0028468 A1) and Eavey et al. (US 2005/0123520 A1) as applied to claim 1 above, and further in view of Colter et al. (US 2013/0183756 A1).
Re claim 26:
Becker does not explicitly rat collagen. Colter et al. (US 2013/0183756 A1) teaches an invention related to an isolated mammalian internal mannnary artery-derived cell. Colter teaches 26. The method of claim 1, wherein the collagen is rat collagen (Colter, [0044]; [0048]). Therefore, in view of Colter, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method described in Becker, by providing rat tail collagen, since it was known in the art to apply collagen to treat wound of the same species of animal.
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over in Becker et al. (US 2018/0028468 A1) and Eavey et al. (US 2005/0123520 A1) as applied to claim 1 above, and further in view of Bosanac et al. (US 2022/0008405 A1).
Re claims 28 – 29:
Becker does not explicitly disclose NAMPT inhibitor. Bosanac teaches a method of treating neurodegeneration and neurodegenerative diseases comprising administering to a subject in need thereof a combination of a SARMl inhibitor and a neuroprotective agent (Bosanac, Abstract). Bosanac teaches 28. The method claim 1, wherein the senescence-inducing agent is a nicotinamide phosphoribosyltransferase inhibitor. 29. The method of claim 28, wherein the nicotinamide phosphoribosyltransferase inhibitor is Daporinad (FK866) (Bosanac, [0078]; [0361]; [0365]).
Therefore, in view of Bosanac, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method described in Becker, by providing the FK866 inhibitor as taught by Bosanac, since NAMPT inhibitor is a drug that targets and blocks the activity of the enzyme NAMPT (nicotinamide phosphoribosyltransferase). NAMPT is crucial for the biosynthesis of NAD+ (nicotinamide adenine dinucleotide), a vital molecule for many cellular processes (Bosanac, [0083], “NAMPT is the rate-limiting enzyme in the Nicotinamide adenine dinucleotide”).
Response to Arguments
Applicant's arguments filed 3/5/2026 have been fully considered but they are not persuasive.
Applicant submits that Becker is concerned with scaffolds for the sustained delivery of anti-connexin 26 and anti-connexin 43 modulators to promote wound healing (see, e.g., [0253-0254]). These modulators are described as agents that modulate the transport of molecules into and out of cells (e.g., blocking or inhibiting or downregulating) ([0132]). In contrast to the presently amended claims, Becker does not disclose or suggest a composition containing both a scaffold and a senescence inducing agent that would induce a foreign body reaction within a wound nor generate a wound model (emphasis added).
While Becker teaches that the gap junction modifying agent may include or exclude doxorubicin (and other anthraquinone derivatives), Becker does not teach or suggest a composition containing doxorubicin (or other anthraquinone derivatives) that would necessarily induce a foreign body reaction within a wound of an animal, thus allowing a wound model to be generated. There is no exemplification of any composition that would induce a foreign body reaction within a wound of an animal and allow a wound model to be generated.
Regarding “Foreign body Reaction” or “FBR”, Applicant’s published application, para. [0042] and [0063] state “the composition is capable of inducing a foreign body reaction (FBR) within the wound of an animal”. Applicant’s para. [0005], states “a composition comprising a scaffold and a senescence-inducing agent”. Furthermore, in para. [0053] states “The senescence-inducing agent may include DNA damaging agents, reactive oxygen species … aphidicolin, bleomycin, cisplatin, doxorubicin, etoposide, mitoxantrone, retinals, hydroxyurea, carboplatin or docetaxel …” (Applicant’s, [0053]). The added limitation does not explicitly define in the claim which chemical compound(s) that requires to induce a foreign body reaction within the wound. Furthermore, applicant’s specification is not clearly on which chemical compounds require to induce FBR. Additionally, it is the examiner’s position that the ability for senescence-inducing agent to induce a foreign body reaction (FBR) varies from animal to another animal and compound to another compound. Some animals have more severe response to one type of senescence-inducing agent to another type. This limitation adds little weight to the claims.
Since applicant’s original disclosure is not clear on which chemical compound(s) induces FBR, the office can only rely on the definition of a senescence-inducing agents defined in the specifications which applicant claimed to be able to induce FBR. Becker’468 teaches the explicitly definition of senescence-inducing agent; for example: (Becker, [0077], “preparing scaffolds coated with one or more polymers with anti-Cx antisense polynucleotides”; [0223], “the scaffolds were soaked in a thermo-reversible medium containing connexion 43 antisense oligodeoxynucleotides”; [0371]; [0206], “gap junction modifying agent may include or exclude, for example … doxorubicin (and other anthraquinone derivatives)”)).
Eavey teaches a method of creating a mold where a "hydrogel" is a substance formed when an organic polymer (natural or synthetic) is set or solidified to create a three-dimensional open-lattice structure (Eavey, [0013]). The cells are then suspended in a hydrogel, such as 2% alginate, to produce a hydrogel-cell composition … The hydrogel-cell composition can be introduced into the mold simultaneously with a curing composition (Eavey, [0035]). The newly cited reference: Yadav et al. (US 2019/0015468 A1) states: “… Some reports describe that alginate used in wound care products may cause long term foreign body type reaction”.
Conclusion
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/JACK YIP/Primary Examiner, Art Unit 3715