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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 2, 2025 has been entered.
Election/Restrictions
Applicant has amended the claims from the elected method of producing a three-dimensional autologous fat graft (see election, 10/8/2024) to formulation. Applicant is remined cannot file an RCE to obtain continued examination on the basis of claims that are independent and distinct from the claims previously claimed and examined as a matter of right (i.e., applicant cannot switch inventions). See 37 CFR 1.145. Typically, any newly submitted claims that are directed to an invention that is independent and distinct from the invention previously claimed will be withdrawn from consideration and not entered. See MPEP 706.07(h).
However, the examiner is in agreement to examine the amended claims limited to the formulation with the RCE filed 10/2/2025.
Status of Claims
Claims 1 and 5-22 are pending. Claims 2-4 are canceled. Claims 21-22 are newly added. Claims 1, 5-15 and 19-20 are amended.
Claims 16-18, are withdrawn as being drawn to a non-elected invention or species, there being no allowable generic or linking claim.
Claims 1, 5-15 and 19-22 are examined on their merits.
Previous Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Rejections Maintained/New Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, 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, 5-9 and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. US 2018/055971 (3/1/2018) (3/23/2021 IDS) in view of Zhu et al. US 2013/0303750 (11/14/2013) and Lou et al. CA 2884367 (4/3/2014) is maintained.
Yu et al. (Yu) teaches hydrogels comprising a hydrogel composition including a cellular component such as human adipose tissue (lipoaspirate), such as adipose-derived stem cells, stromal vascular fraction cells. (See Abstract and [0045]). The hydrogel composition comprises a lipoaspirate with a co-crosslinked HA-silk fibroin composition. (See Abstract).
Yu thus teaches a hydrogel comprising a hydrogel composition including a cellular component such as human adipose tissue (lipoaspirate), such as adipose-derived stem cells, stromal vascular fraction cells by mixing the lipoaspirate with an excipient as called for in instant claim 1. (See [0045], [0051] and Examples 2 and 12). The co-crosslinked HA-silk fibroin composition is an excipient that is a biocompatible material.
Yu also teaches the making of the hydrogels by mixing the lipoaspirate with an excipient wherein the mixture is crosslinked. (See [200] and Examples 1-5 and 12). Yu specifically teaches that the hydrogels can be formed with an EDC crosslinker and NHS as an activating agent. (See [0073]). Yu teaches that the hydrogel is porous and is suitable as a substrate for applications requiring very high tensile strength, such as bioengineered tendons. (See [0106]).
Yu teaches at [0046] that when injected to implanted in vivo, a hydrogel or hydrogel composition may promote cell and or tissue growth. A hydrogel or hydrogel composition can stimulate neovascularization in vivo. (See [0046-0047]). Thus, the hydrogel is configured to allow for neovascularization upon or after implantation as called for in instant claim 20. (See [0046]; Example 12).
Yu also teaches that its hydrogel composition shows improved volume retention after injection or implantation into a soft tissue. (See [0052-53]). This is operative to be used for aesthetic surgical purposes as called for in instant claim 21, since Yu teaches that its hydrogel composition shows good volume retention after both injection into a soft tissue or implantation into a soft tissue.
Yu thus teaches that the hydrogel is porous and exhibits good volume retention upon implantation which means that there is not substantial volume shrinkage upon or after implantation into a human as called for in claim 19.
Yu teaches that the hydrogel can be used in aesthetic surgery via implanting as called for in claim 20. (See [0083]-[0084]). The hydrogel is configured to allow for neovascularization upon or after implantation. (See [0046-0047]; Example 12). This is a formulation that is configured to form one or more three-dimensional autologous fat graft before, during or after implantation into a human as called for in instant claim 22.
Yu does not teach cellulose nanofibrils or cellulose nanofibrils that are obtained from tunicates. This deficiency is made up for with the teachings of Zhu et al. and Lou et al.
Zhu et al. (Zhu) teaches cellulose nanofibrils that have been produced from cellulose using milder acid hydrolysis conditions. (See Abstract). Zhu teaches that cellulose nanofibrils can be made from tunicates, and that tunicates are a natural cellulose source material. (See [0041]). Zhu teaches that the cellulose nanofibrils are also referred to as (CNFs). (See [0035]). Cellulose nanofibrils are called for in instant claim 1. Cellulose nanofribrils made from tunicates are called for in instant claim 1. Cellulose nanofibrils derived from tunicates is called for in instant claim 22.
Zhu teaches that its CNFs are from about 100 nm to 5000 nm (which is 0.1 to 5 micrometers/microns) which overlaps with the fibrils with a length between 0.1 microns and 5 microns called for in instant claim 5. (See [0035]). Zhu teaches a dispersion of the CNFs. (See [0047]). Since Zhu teaches that the CNFs can be derived from tunicates, the CNFs comprise a dispersion having no bacteria derived lipopolysaccharides as called for in instant claim 9.
Lou et al. (Lou) teaches hydrogel bodies comprising cellulose nanofibrils. (See page 4). The solid content of the CNF containing hydrogel in the CNF hydrogel stock solution is 1.8% w/v which falls within the greater than 1.5% and less than 4% by weight called for in instant claim 6. (See Examples). Lou teaches that the CNFs may contain some hemicelluloses. Lou also teaches that the composition can vary depending on the chemical composition of the raw material used for production of the CNF. In light of this teaching a skilled artisan would be able to manipulate the amount of hemicellulose to the desired amount that would not affect a human’s immunoresponse system as called for in instant claim 7.
Lou teaches that CNFs form hydrogels with tunable physical and chemical properties and diverse pharmaceutical and biomedical applications. (See page 4). Lou also teaches that the hydrogel is homogeneous, so the CNF does not have detectable agglomerates as called for in claim 8. (See claim 12). A dispersion is taught in Figures 19 and 20 and a hydrogel is taught in Lou to be an aqueous dispersion of cellulose nanofibrils having a homogeneous and continuous cell structure. (See lines 23-27 of page 9).
It would have been prima facie obvious for one of ordinary skill in the art making the Yu hydrogel to mix the co-crosslinked HA-silk fibroin composition with the lipoaspirate so that it can be implanted into the body so that it can be used to enhance the aesthetics of a human patient by exhibiting good volume retention after injection or implantation into a soft tissue as taught by Yu.
It would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Yu hydrogel to use CNFs with a length of from 0.1 to 5 micrometers derived from tunicates in order to have naturally sourced CNFs that can be made using milder acid hydrolysis conditions as taught by Zhu.
It would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Yu hydrogel to make homogenous hydrogels with 1.8% w/v CNF as taught by Lou in order to have homogeneous hydrogels with tuneable physical and chemical properties and diverse pharmaceutical and biomedical applications as taught by Lou.
The rejection of claims 10-15 under 35 U.S.C. 103 as being unpatentable over Yu et al. US 2018/055971 (3/1/2018) (3/23/2021 IDS) in view of Zhu et al. US 2013/0303750 (11/14/2013) and Lou et al. CA 2884367 (4/3/2014) as applied to claims 1, 5-9 and 19-22 and further in view of Gatenholm WO 2017/214592 (6/9/2017) is maintained.
The teachings of Yu in view of Zhu and Lou are described supra. Yu in view of Zhu and Lou does not teach crosslinking of the CNF by fibrinogen and thrombin. This deficiency is made up for with the teachings of Gatenholm.
Gatenholm teaches the modification of cellulose nanofibrils (CNF) with extracellular matrix components such as collagen, elastin or growth factors. (See Abstract). Cellulose nanofibrils provide excellent printing fidelity which is crucial for the diffusion of oxygen and diffusion of nutrients into the biological constructs.
Gatenholm teaches that it is beneficial for its invention for the CNF to be crosslinked. (See [001]). Gatenholm teaches that the CNF can be crosslinked with fibrinogen and thrombin. Crosslinking CNF with fibrinogen and thrombin is called for in instant claim 12.
Another way of crosslinking CNF is to add alginate and calcium chloride, which being a salt will result in calcium ions. Crosslinking CNF with alginate and calcium ions is called for in instant claim 10. Using either method, the CNF is crosslinked.
Claims 11, 13, 14 and 15 contain limitations regarding how the compositions are made. However, the compositions are not limited to the manipulation of the process of making the product. “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). Furthermore, “[b]ecause validity is determined based on the requirement of patentability, a patent is invalid of a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” Amgen Inc. v. F. Hoffman-La Roche Ltd. 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009); Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733.
It would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Yu in view of Zhu and Lou hydrogel to make hydrogels with CNF crosslinked by adding alginate and calcium chloride as taught by Gatenholm in order to allow for the maximal diffusion of oxygen and diffusion of nutrients into the resulting hydrogel biological constructs as taught by Gatenhom.
Response to Arguments
Applicants’ arguments of October 2, 2025 have been fully considered and are found to be unpersuasive.
Applicants note the amendment to the claims and where support for the amendment can be found.
Applicants assert that the claimed invention is to a combination of tunicate nanofibrillar cellulose and lipoaspirate for specific purposes/outcomes. Applicants assert that they believe the Office mostly accepted Applicants previous arguments as to the distinct nature of tunicate nanocellulose fibrils compared to the protein-based silk fibroin scaffolds disclosed by Yu.
Applicants argue that Yu does not disclose lipoaspirate mixed with nanofibrillar cellulose derived from tunicates. Applicants assert that this feature has the novel and unexpected technical effects of having favorable mechanical, process and purity characteristics over bacterial and plant-derived cellulose and nanocelllose. The durability is improved and lasts longer compared to what is achievable using silk/hyaluronic acids hydrogels such as disclosed in Yu.
The tunicate-derived nanocellulose hydrogels of the current invention have several important distinguishing technical features that could not be predicted by those skilled in the art of making silk/hyaluronic acid hydrogels and are not suggested by Yu, including
Applicants assert that while the Lou references does indeed teach that the plant cellulose/nanocellulose hydrogels can be used in combination with Adipose Stem Cells, it would not be obvious to one of skill in the art that the use of Adipose Stem Cells in Lou could be replaced by the lipoaspirate, regardless of the source of the cellulose used to make the nanocellulose hydrogel.
Applicants assert that there are functional differences that cannot be anticipated by the use of ASCs based on Applicants experiments, including lipoaspirate includes other components in addition to ASCs, such as stromal vascular fragments and stromal vascular fragments permit rapid vascularization of the hydrogel based grafts that cannot be obtained with ASCs alone. Applicants assert that the grafting product proposed by Lou could only be used for small, diffusion-limited grafts of narrow biomedical interest. In contrast, the instant invention can be used for much larger grafts of much wider biomedical interest.
Applicants’ obviousness arguments have been carefully reviewed and are not found to be persuasive. As an initial matter, respectfully, Applicants are incorrect in their belief the Office mostly accepted Applicants previous arguments as to the distinct nature of tunicate nanocellulose fibrils compared to the protein-based silk fibroin scaffolds disclosed by Yu.
As noted in the Arguments section on page 10 of the Final Rejection of July 3, 2025, it was only in light of the amendments to the claims that the rejections were withdrawn. Nowhere was it stated that Applicants’ arguments were persuasive absent the amendments to the claims.
Yu does not disclose lipoaspirate mixed with nanofibrillar cellulose derived from tunicates, but Zhu teaches that cellulose nanofibrils can be made from tunicates, and that tunicates are a natural cellulose source material. (See [0041]).
With respect to Applicants arguments that the claimed invention is to a combination of tunicate nanofibrillar cellulose and lipoaspirate for specific purposes/ outcomes, it should be noted that Applicants have just amended all of their claims to become composition claims and much of the language of the specific purposes is language of intended use.
With respect to claim 1’s language of “for a three-dimensional autologous fat graft” this is language of intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, as it is in this instance, then it meets the claim.
As described in the rejection above, the formulation is configured to form one or more three dimensional fat grafts before, during or after implantation into a human or animal as called for in instant claim 22 because Yu teaches that the hydrogel is suitable for use in aesthetic surgery via implantation. (See [0083]-[0084]). Indeed, one of the objects of the Yu invention are hydrogels comprising a macromolecular matric and water that may be used to augment the soft tissue of a human being, promote or support cell or tissue viability or proliferation. (See Yu Abstract).
Yu teaches at [0046] that when injected or implanted in vivo, a hydrogel or hydrogel composition may promote cell and or tissue growth. A hydrogel or hydrogel composition can stimulate neovascularization in vivo. (See [0046-0047]). Thus, the hydrogel is configured to allow for neovascularization upon or after implantation as called for in instant claim 20. (See [0046]; Example 12).
Applicants’ arguments that it would not be obvious to one of skill in the art that the use of Adipose Stem Cells in Lou could be replaced by the lipoaspirate are not found to be persuasive. Respectfully, Applicants assertions that there are functional differences that cannot be anticipated are all based on Applicants experiments. This is not conventional wisdom in the art at or before the time of the earliest effective filing date of the invention or a teaching away that is found in the prior art at that time. Applicants have not pointed to anything in the prior art before the earliest effective filing date that would discourage the person of ordinary skill in the art from combining the teachings of the prior art references.
Additionally, Applicants’ assertions are directly contradicted by the prior art references themselves. As described in the rejection above, it would have been prima facie obvious for one of ordinary skill in the art before the earliest effective filing date making the Yu hydrogel to make homogenous hydrogels with 1.8% w/v CNF as taught by Lou in order to have homogeneous hydrogels with tuneable physical and chemical properties and diverse pharmaceutical and biomedical applications as taught by Lou
Applicants’ assertion that the grafting product proposed by Lou could only be used for small, diffusion-limited grafts of narrow biomedical interest, but the instant invention can be used for much larger grafts of much wider biomedical interest appears to be directly contradicted by Zhu’s assertion that the hydrogels have tunable physical and chemical properties and diverse pharmaceutical and biomedical applications.
Finally, even assuming, arguendo, that Applicants’ assertion is true, the scope of the instant claims still covers small, limited grafts of narrow biomedical interest. There is no requirement in the claims that grafts be large and of wide biomedical interest. The claims cover the grafts, regardless of size and degree of biomedical interest. Thus, the prior art teachings render the claims obvious as they are drafted.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH CHICKOS whose telephone number is (571)270-3884. The examiner can normally be reached on M-F 9-6.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAH CHICKOS/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619