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 05/05/2026, 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 Any previous rejection or objection not mentioned herein is withdrawn.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 1-4, 6, 8, 12, 14-15, 18-19, 27, 32-33, 39-40, 42-44 are pending of which claims 1-4, 6, 15, 27, 32-33, 39-40 and 42-44 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on
Claims 8, 12, 14 and 18-19 are being examined on the merits.
Claim Objections
Claim 8 is objected to because of the following informalities: The claim recites abbreviations intended for cell types (EKs, DFs and MSCs). Although the applicant describes these in the specifications it is proper to spell the words out the first time they are being read as to clarify their meaning. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 8, 12, 14, 18-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite a hydrogel composition comprising of collagen, dermatan sulphate, agarose, hyaluronic acid, sphingolipids, keratin, epidermal keratinocytes, mesenchymal stem cells and dermal fibroblasts. The first step of the eligibility analysis evaluates whether the claim falls within a statutory category (see MPEP 2106.03). Since the claim is directed to a composition comprising components found within humans the claims are a composition of matter. Step 2A prong one of the analyses evaluates whether the claim is a judicial exception (see MPEP 2106.04). Because the claim states the nature-based products collagen, dermatan sulphate, agarose, hyaluronic acid, sphingolipids, keratin, epidermal keratinocytes, mesenchymal stem cells and dermal fibroblasts, the markedly different characteristics is performed by comparing the nature-based product limitation to its natural counterpart.
The claim recites the naturally occurring components found within humans except for the agarose which is naturally existing polysaccharide found in seaweed. In this case the applicant merely claims a combination of the naturally existing judicial exceptions which are the components recited above. Claiming cells no matter the cell type and components secreted from cells such as complex sugar molecules and types of collagens is still claiming those judicial exceptions. The closest naturally occurring counterparts are those same molecules, compounds, cells found already existing in nature and these are chemically identical to those being compared to. All of these are naturally occurring in nature and are not markedly different from its naturally occurring counterpart in its natural state. The properties of the nature-based product as claimed are not markedly different than the properties of these naturally occurring counterparts found in nature as these activities would inherently be found stemming from those components. The components which would give the activities claimed in the instant invention would inherently do the same in nature as there has been nothing done in the instant invention that would make them act in any different way.
Step 2A prong two evaluates whether the claim as a whole integrates the recited judicial exception into a practical application (see MPEP 2106.04(d)). This evaluation is performed by (a) identifying whether there are any additional recited elements in the claim beyond the judicial exception and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. This judicial exception is not integrated into a practical application because the applicant is merely claiming the judicial exceptions together without reciting some practical application and the other limitations are only to the amounts of those judicial exceptions. Doing so would be implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
The claims do not integrate the judicial exceptions into a practical application because in this context, such integration for a claimed product would be a physical form of the specific practical application instead of a more general composition that is not so limited.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these components and their activity are already found naturally occurring in nature and the addition of an intended use does not impart any added benefit to the compounds or integrate the composition into a practical application.
Step 2 B evaluates whether the claim as a whole, amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP § 2106.05(b)).
Since the naturally-occurring components (e.g. agarose) as-claimed are not found together in nature, admixing the ingredients into a single formulation is considered an ‘additional element’ which must be analyzed for eligibility. Admixing naturally-occurring cells and cellular components in a manner similar to what the applicant claims is routine practice in the art as evidence by at least the following documents: US20040170615A1, US20050058629A1, US20040078090A1, US7211648B2, US20080031962A1.
Please also note, the mere modifying the concentration and proportions of the product/composition is not sufficient to remove the claimed composition from a judicial exception.
Therefore, admixing the claimed naturally-occurring ingredients at such a high degree of generality merely involves applying the natural principal and appears to be no more than a drafting effort to claim the judicial exception itself; a mixture of naturally-occurring components that is not markedly different from its’ closest-occurring natural counterpart and which does not offer significantly more than the judicial exception.
Although the applicant provides data showing that the cells and cellular components when combined together can support the growth of new cells to treat skin regeneration, these components (the cells and cellular components being claimed) are already known to do so in nature. Combining agarose which is not found within the human skin to the composition would act in a similar manner as it does in nature as it is a polysaccharide known for forming hydro(gels). Combining collagen, keratin, hyaluronic acids, dermatan sulfate, sphingolipids etc. together with an expectation that they will support the growth of new tissues is expected as these proteins and glycosaminoglycans and sphingolipids do the same in the human skin naturally.
Response to Arguments
Applicant's arguments filed 05/05/2026 have been fully considered but they are not persuasive. The applicant argues that there is no natural counterpart to the composition being claimed. The components of the composition are the natural counterparts. Each of these different cell types and molecules claimed are found within skin and different parts of skin indeed form hydrogels especially in the extracellular matrix. Adding agarose to a mixture of different cells and molecules found within skin and expecting them to form a hydrogel is not an expected feature as agarose is used for its gelling properties.
The applicant argues that the specific trilaminar formulation is differently structured when compared to the cells structures naturally found in skin. The cells and molecules themselves are what is being compared, not skin as an organ. The cells and molecules’ structures have not changed in any way structurally or functionally. Merely rearranging them differently as how they are found within skin and expecting their properties to remain the same does not overcome the rejection.
The applicant argues that since the composition is indeed engineered and in a non-naturally occurring hydrogel scaffold which is a clear hallmark of human ingenuity that this difference shows how the composition cannot be naturally found. Removing the judicial exceptions outside their naturally occurring place of origin and/or habitat does not overcome the rejection simply because they are now claimed in a different grouping/formation. The judicial exceptions themselves are being analyzed to see if there has been some characteristic imposed on them to have them have different structures and/or functions. Also as pointed out before the claimed skin molecules indeed exist in naturally occurring hydrogels. Agarose also creates hydrogels naturally as do components of the skin ECM. Claiming components that already exist in hydrogel formation and arguing that the structures of those components have changed does not change those cells, molecules, etc. because sphingolipids, dermatan sulphate, collagen and hyaluronic acids do exist within hydrogels naturally in the body. Hydrogels are simply three-dimensional, cross-linked networks of hydrophilic polymers capable of absorbing and retaining large amounts of water. Thus these states are natural to the molecules as they indeed are hydrophilic polymers. The cells claimed come in contact with ECM and the hydrogel formations they create.
The applicant argues that agarose provides the necessary mechanical stability and rapid thermos-reversible gelation that allows for the creation of a highly organized, trilaminar scaffold. The applicant is arguing the agarose’s natural abilities to act as a hydrogel as agarose is a high-molecular-weight, linear polysaccharide extracted from red seaweed, which is known to exert the exact properties being argued. There has been nothing done to the agarose to change its properties and these properties are to be expected. Agarose has been used for its hydrogel forming properties in molecular science to separate out molecules based on their size and charge in agarose gel electrophoresis assays. The more agarose which is added during the assay the smaller the pore sizes become in which the molecules can pass through. The less agarose that is added the gel becomes less rigid and the more freely molecules are able to pass. The applicant argues that the composition is deliberately engineered to promote skin regeneration, however the components of the composition already exert the properties for skin renewal because those properties come from the cells and molecules being claimed, not from the arrangement of those components, unless shown some evidence that this is indeed not the case.
The applicant argues that since adding agarose to the composition, it is a non-human component which is not found in human skin and it promotes gelling formation. Agarose is still yet another judicial exception which is being claimed and analyzed. The properties of agarose have not changed. Also, it is not skin which is being compared in the analysis. It is the individual judicial exceptions being compared. The applicant’s argument which compares their invention to skin is not a proper argument for rebutting the 101 analysis. Just because the applicant has included a non-human judicial exception in the composition with judicial exceptions found within humans does not mean that the composition being claimed is not made up of only judicial exceptions.
The applicant argues that the composition has different structures because it was engineered from “bio-ink” through 3D printing which allows it some novel function. This argument does not point to what structures have changed and/or what the new novel functions are.
The applicant argues that there is no natural arrangement of cells in such a trilaminar structure as being claimed in claim 8. The rearrangement of cells does not exclude them from the analysis and does not change the cells structures and/or functions.
The applicant argues that agarose provides the necessary mechanical stability and rapid, thermo-reversible gelation. These are properties already known to come from agarose. The applicant is merely pointing them out. These properties are excepted from adding different concentrations of agarose.
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.
Claims 8, 12, 14, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Burkhard Mathies (EP2827914B1), Suchitra Sumitran-Holgersson (WO2017076782A1) and Sonia Borodzicz et. al. (The role of epidermal sphingolipids in dermatological diseases, Lipids in Health and Disease (2016) 15:13). This rejection is maintained with slight modifications due to the amendment’s files on 05/05/2026.
Mathies teaches compositions which include collagen and hyaluronic acid for use in a method for repair of a ligament or tendon in a subject and teaches the collagen can be type I (see claim 1 and 0038). The composition comprises of three layers which comprises of collagen and being cell porous, a matrix layer comprising of hyaluronic acid and a third layer which is disposed on the matrix layer such that the matrix later is sandwiched between the support and third layer (see claim 1). Mathies teaches wherein the matrix can comprise of dermatan sulfate (see 0087 and 0089) and agarose (see 0168).
Mathies teaches wherein collagen-glycosaminoglycan (CG) copolymers have been used successfully in the regeneration of dermis (see 0084).
Mathies teaches wherein in various embodiments the matrix comprises of hydrogels (see 0065, 0067-0068).
Mathies teaches that “hyaluronic acid, also called hyaluronan or hyaluronate, is a glycosaminoglycan. It is a naturally occurring biopolymer having biological functions from bacteria up to higher animals including humans. In animals, it is one of the chief components of the extracellular matrix. It contributes significantly to cell proliferation and migration”. (see 0069).
Mathies teaches adding MSCs and in the presence of collagen will differentiate into fibroblasts (see 0159) and specifically teaches culturing the composition with fibroblasts (see 0185-0189).
Mathies teaches it is well known that injury-healing fibroblasts have a special affinity for collagen and certain other biopolymers. This property is termed the chemotactic effect for collagen (see 0023)
Mathies does not specifically teach wherein the composition contains sphingolipids in the top layer of the hydrogel or teach adding epidermal keratinocytes.
Borodzicz teaches that “sphingolipids have both structural and biological functions in human epidermis [1, 2]. The barrier between the environment and the human body is maintained by the stratum corneum (SC), the most external layer of the epidermis. The stratum corneum is composed of terminally differentiated keratinocytes and extracellular lipids, such as ceramides (CER), cholesterol and free fatty acids in almost equimolar quantities. The main function of these lipids in the stratum corneum is the formation of the skin barrier and the prevention of transepidermal water loss (TEWL) [1, 3]. Ceramides are among the most important epidermal sphingolipids and compose about 50 % of intercellular stratum corneum lipids by mass [3]” (see page 1 background 1st para.).
“Other than the structural function in the epidermis, sphingolipids also play an important role in epidermal signaling. Ceramides regulate such processes as proliferation, differentiation and apoptosis [31]” (see page 2, 2nd para.).
“In vitro investigation revealed that sphingosylphosphorylcholine added to the cultures of human keratinocytes enhanced their proliferation and promoted wound repair by stimulating migration and/or proliferation of the keratinocytes to the denuded areas of keratinocytes monolayers” (see page 2, 3rd para.).
Borodzicz teaches human dermal fibroblasts being cultivated on the bio-compatible repair patch composition (see 0186) and teach also using MSCs (see 0024, 0133 and 0159).
Regarding claim 14, Borodzicz teaches the matrix layer to be lyophilized (see 0081-0082).
Sumirtan-Holgersson’s general disclosure is to compositions and methods for healing wounds.
Sumirtan-Holgersson teaches of similar components for skin healing. Sumirtan-Holgersson teaches “the higher amounts of collagen in the composition (e.g., an engineered biomaterial (e.g., gel composition)) of the present disclosure may promote more rapid infiltration of host cells to the wound and more prompt wound stabilization” (see 0054). Sumirtan-Holgersson teaches that the biomaterial may contain agarose (see 0049) and the biomaterial of the present disclosure may be in a gel form, sponge form, foam form, patch form, or a semi-liquid/fluid form. The biomaterial may be in gel form (see 0050).
Sumirtan-Holgersson teaches keratinocytes regulate fibroblast behavior through the production of pro- and anti-fibrotic soluble factors, and that the production of those factors is dependent on the hydration state of the keratinocytes (see 0038) and teaches wherein keratin is produced from the keratinocytes migrating to the composition (see figure 4d and 0015). Sumirtan-Holgersson teaches
Therefore it would have been obvious to persons having ordinary skill in the art before the effective fling date to use sphingolipids in a top layer because as discussed by Borodzicz, sphingolipids play important structural and functional roles in skin epidermal signaling and proliferation of keratinocytes which can ultimately promote wound repair. Additionally, it would have been obvious to create a trilaminar hydrogel comprising of two laminar layers comprising of Type I collagen, dermatan sulfate, hyaluronic acid, keratin and agarose as these components are known for being compiled into layers for creating a matrix and to act as copolymers and structural proteins for successfully regenerating the dermis. Mathies teaches creating three layers comprising of matrices and support layers to heal tissues and teaches including the same beneficial cells and cell components as claimed. Furthermore, Sumirtan-Holgersson teaches how biocompatible compositions with hyaluronic acid and collagen can help to recruit keratinocytes which deposit keratin into the biocompatible matrix composition and keratin is a known fibrous structural component which provides support and protection in skin. Hyaluronic acid is a glycosaminoglycan which is known to support cell proliferation and migration. Agarose is a supportive polysaccharide which helps to form the hydrogel composition because it is known to form a gel when cooled after being dissolved in water. Dermatan sulfate is a glycosaminoglycan (GAG) found in the extracellular matrix, essential for tissue development and function and collagen type I provides structure and strength to connective tissues. Each of these components have a known particular effect in assisting with the development of wound repair and within connective tissues and extracellular matrices. Each would be an optimizable parameter because one would need to optimize each to be within an effective amount that would contribute to wound repair and tissue healing dependent upon which tissue is targeted and so it would have been obvious to optimize the components to be within the instantly claimed range. This would have been an optimization well within the purview of the skilled artisan unless shown some unexpected results from the applicant. Thus combining the active components claimed into compositions which would be three layers for healing skin would have been obvious given the prior art.
Response to Arguments
Applicant's arguments filed 05/05/2026 have been fully considered but they are not persuasive. The applicant argues that the primary reference, Mathies is concerned with creating patches for repairing ligaments and tendons and not for creating a substitute for human skin. The applicant merely claims a trilaminar hydrogel comprising specific components. The intent for the composition or the reason for creating the composition does not have to be the same as that as the applicants. Mathies indeed teaches including a third support layer which can be skin (see 0134-0135, claim 3, 008, 0010 and 0047-0053). Creating three-layer hydrogels comprising of the instantly claimed components for healing wounds is prima facie obvious especially given the relied upon art. The art teaches creating patches, gels, hydrogels, etc. for healing wounds comprising of the same components. Each molecule and cell have a specific role in wound repair formulations as discussed in the above rejection. Although the applicant may argue that the invention is intended for skin repair, the applicant’s claims are not particularly limited to anything more than a trilaminar hydrogel formation.
The declaration under 37 CFR 1.132 filed 05/05/2026 is insufficient to overcome the rejection of the claims based upon 35 U.S.C. 103 as set forth in the last Office action because: the applicant argues that the properties of the specific formulation exert some synergistic effects rather than some mere averaging of products. This does not appear the be the case. The applicant argues that there are differences between the agarose contained layers versus the non-agarose contained layers because the agarose layers exhibit an interconnected porous architecture with larger pores, thinner pore walls and smoother continuous regions. The applicant is merely arguing the properties of agarose which are wildly known. The more agarose added would be expected to create stabilizing gel formations with limiting pore sizes in which molecules can pass. The applicant argues different gel kinetics further highlighting the effects of agarose. These too are properties known of agarose. The applicant argues that it would not be expected that the sub-minute gelation property would exist along with a porous architecture, but these gelling properties and porous architectures are dependent on the concentration of agarose being added and are predictable. The applicant argues that agarose reduces gelation time compared to non-agarose compositions however this is a property of agarose. Agarose forms gels and its ability to reduce gelation time because it is a hydrogel forming polymer is expected. The applicant argues that although that property may be expected, it would not be expected to have sub-minute gelation time with a porous architecture. But this is expected because the ability to form gels creates the porous structures which allows for molecules or cells to pass. The applicant’s statements are not supported by evidence that this would not be expected and mere conclusory. The applicant argues that the agarose free hydrogel formed flaccid gels that were difficult to manipulate. This too is expected as the agarose supplies a supporting gel-forming structured support.
The applicant argues that the collagen hydrogel exhibited a storage modulus in the order of 102 Pa whereas the agarose alone displayed a storage modulus of 104-105 Pa and the collagen-agarose blend displayed a storage modulus of approximately 104 Pa. The applicant believes this combination which shows a magnitude of two orders of magnitude greater than the collagen alone is not predictable, however given the agarose already contributes to an increase of two orders of magnitude, this increase is expected and predictable. The applicant argues that although one may want to interpret this evaluation as additive that the characterization of adding agarose and collagen would be expected to either create a stiff rigid formation which does not allow a porous structure. This is not true. It is the amount of agarose added not merely the component itself which is known to contribute to its structure and porosity. It is concentration dependent. Agarose gel is known to both be porous and exert stabilizing properties as what is being argued. The applicant argues that it is not expected that the increased stiffness from the addition of agarose would be accompanied by increased porosity. Again it depends on the amount being added. The applicant does not show that the porosity increases with increased amounts of agarose. Even if this is the case the applicant does not show the criticality of the specific amounts for the properties of which they argue. Adding any amounts of the claimed components would not be expected to create the invention being argued. Does claim 12 recite these particular amounts that may not be expected and predictable as being argued. Perhaps claiming the invention to a scope that is tied to particular activities will help to overcome the art. As currently claimed the applicant is merely claiming a hydrogel even if they have a specific intended use for it. It is also reminded that merely reciting an intended use may not be enough to overcome the art if the intended use does not structurally or functionally change the composition. The examiner has been in contact with the applicant to try and suggest changing formulations to overcome the 101 and to narrow the scope or to tie the activities to the composition which may help overcome the art.
Conclusion
Currently 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
Prosecution Insights