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 .
Claims 1, 2, 4, 5, 7-12 and 29 are pending in this application and were examined on their merits.
The Petition to Color Drawings under 37 C.F.R § 1.84(a)(2) has been received. Final disposition of the petition is decided by the Examiner’s Supervisory Patent Examiner.
The objection to the Specification due to the improper use of Trademarks has been withdrawn due to the Applicant’s amendments to the Specification filed 10/10/2025.
The rejection of Claims 1 and 3-13 under 35 U.S.C. § 112(a) or 35 U.S.C. § 112
(pre-AlA), first paragraph, as failing to comply with the written description requirement, has been withdrawn due to the Applicant’s amendments to the claims filed 10/10/2025.
Claim Interpretation
The preamble of Claim 1, “a biological tissue regeneration” patch is a statement
of the purpose or intended use of the composition, however the body of the claim fully
and intrinsically sets forth all of the limitations of the claimed invention. Therefore, the
preamble is not considered a limitation and is of no significance to claim construction.
The intended use does not result in a structural difference between the claimed
invention and the prior art as set forth below. See the MPEP at 2111.02, Il.
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.
Claims 1, 5 and 7 are newly rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Li et al. (WO 2007/090102 A1), cited in the IDS, as necessitated by Applicant’s amendments to the claims filed 10/10/2025.
Li et al. teaches a composition comprising a fibrous polymer scaffold (Pg. 72,
Claim 1), wherein the polymer is the biocompatible polymer polycaprolactone (inherently biodegradable) (Pg. 72, Claim 10), a molecule directly covalently attached/immobilized or indirectly covalently attached/immobilized to the polymer scaffold by a linker (therefore functionalized); wherein the molecule is capable of covalently attaching to a differentiation factor (Pg. 73, Claim 18) and wherein the differentiation factor is Wnt (therefore encompassing all/one or more Wnt proteins) (Pg. 74, Claim 23);
wherein the polymer scaffold can be a sheet (i.e., a film) (Pg. 72, Claim 2);
wherein the composition further comprises stem cells on the polymer scaffold
(Pg. 73, Claims 14-16);
and wherein the stem cells may be in a growth environment in which stem cells
will proliferate in vitro, including a medium and substrate (Pg. 19, Paragraph [0095]),
and reading on Claims 1, 5 and 7.
With regard to the limitation of Claim 1, “wherein the patch promotes asymmetric division of mesenchymal/skeletal stem cells and orientation of tissue formation”, the Examiner notes that the instant claims are directed to a composition and not to its method of use. Therefore, the ordinary artisan would expect that the anticipating composition of Li et al. would also have the same properties and characteristics as the claimed composition, when in use.
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, 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.
Claims 1, 2, 5, 7 and 29 are rejected under 35 U.S.C. § 103 as being unpatentable over Li et al. (WO 2007/090102 A2), cited in the IDS, as applied to Claims 1, 5 and 7 above, and further in view of Morgan et al. (US 6,924,141 B2), of record, as necessitated by Applicant’s amendments to the claims filed 10/10/2025.
The teachings of Li et al. were discussed above.
Li et al. did not teach wherein the one or more Wnt proteins is Wnt3, as required by Claim 2;
or wherein the one or more Wnt protein is Wnt3a, as required by Claim 29.
Morgan et al. teaches that Wnt3 and Wnt3a are Wnt proteins (Column 3, Lines 31-32).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Li et al. which comprises a Wnt molecule directly covalently attached/immobilized or indirectly covalently attached/immobilized to the polymer scaffold by a linker to use either Wnt3 or Wnt3a as taught by Morgan et al. because the composition of Li et al. is not limited to any particular Wnt and Wnt3 and Wnt8a are disclosed in the prior art as Wnt molecules. Those of ordinary skill in the art would have been motivated to make this modification because the composition of Li et al. is drawn to any Wnt protein generically and Morgan et al. teaches specific Wnt proteins. There would have been a reasonable expectation of success in making this modification because Li et al. is drawn to any Wnt and Morgan et al. is drawn to specific Wnt proteins.
Claims 1, 4, 5, 7 and 8 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Li et al. (WO 2007/090102 A2), as applied to Claims 1, 5 and 7 above, and further in view of Lowndes et al. (2017), both cited in the IDS, as necessitated by Applicant’s amendments to the claims filed 10/10/2025.
The teachings of Li et al. were discussed above.
Li et al. did not teach a composition wherein the Wnt is covalently conjugated to the scaffold with primary amine functional groups, as now required by Claim 4;
or wherein the biocompatible polymer is functionalized with primary amine groups, as required by Claim 8.
Lowndes et al. teaches that commercially available surfaces (substrates) can be functionalized for Wnt immobilization, wherein EDC and NHS convert surface carboxylic groups to succinimide ester that can react with nucleophilic groups on the Wnt ligand (e.g. the primary amine) to form an amide (covalent) bond (Pg. 1500, Column 1, Lines 14-20 and Fig. 1a).
The Examiner notes the Specification as published indicates that a polymer surface can be functionalized to provide primary amine functional groups and such functionalization may be achieved by way of activation of carboxylic acid by EDC/NHS reaction (Pg. 3, Paragraph [0033)).
It would have been obvious to those of ordinary skill in the art to modify the
composition of Li et al. which comprises a Wnt molecule directly or indirectly covalently
attached to the polymer so that the polymer is functionalized with primary amine groups
which immobilize the Wnt to the polymer as taught by Lowndes et al. because the
composition of Li et al. is not limited to any particular Wnt immobilization method and
Lowndes et al. discloses a specific method for functionalizing surfaces/substrates for
Wnt immobilization. Those of ordinary skill in the art would have been motivated to
make this modification because the composition of Li et al. is drawn to any covalent
immobilization method generically and Lowndes et al. teaches a specific method for
immobilization of Wnt proteins.
There would have been a reasonable expectation of success in making this modification because Li et al. is drawn to any covalent Wnt protein immobilization method and Lowndes et al. is drawn to a specific Wnt protein immobilization method.
Claims 1, 5, 7, 9, 11 and 12 are newly rejected under 35 U.S.C. § 103 as being
unpatentable over Li et al. (WO 2007/090102 A2), cited in the IDS, as applied to Claims
1, 5 and 7 above, and further in view of Fischer et al. (2012), of record, as necessitated by Applicant’s amendments to the claims filed 10/10/2025.
The teachings of Li et al. were discussed above.
Li et al. did not teach a composition wherein the stem cells are cultured on the
polycaprolactone sheet are overlaid with collagen, as required by Claims 9, 11 and 12.
Fischer et al. teaches that in direct comparison studies with 2D ECMs, engagement of the dorsal (therefore overlying) cell surface by a second planar substrate of either synthetic or collagen gels was sufficient to alter cell morphology and migration in motile cells and had profound effects on the cytoskeletal organization and dynamics, some of which appear to approximate those observed in cells in native 3D environments (Pg. 2056, Column 2, Lines 3-9).
It would have been obvious to those of ordinary skill in the art to modify the composition of Li et al. which comprises stem cells which may be in a growth environment (e.g. cultured) on the polymer scaffold which may be a sheet/film (therefore 2D) to overlay the cells with collagen as taught by Fischer et al. because this would provide a culture environment closer to the native 3D environment and benefits over culturing in a planar 2D environment. Those of ordinary skill in the art would have been motivated to make this modification in order to achieve the effects of altered cell morphology and migration, as well as cytoskeletal organization and dynamics which are more closely associated with native 3D conditions. There would have been a reasonable expectation of success in making this modification because both Li et al. and Fisher et al. are generally drawn to the same field of endeavor, that is, cell culturing.
Claims 1, 5, 7, 9, 10, 11 and 12 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Li et al. (WO 2007/090102 A2), cited in the IDS, in view of Fischer et al. (2012), of record, as applied to Claims 1, 5, 7, 9, 11 and 12 above, and further in view of Kapalczynska et al. (2016), of record, as necessitated by Applicant’s amendments to the claims filed 10/10/2025.
The teachings of Li et al. and Fischer et al. were discussed above.
Li et al. did not teach a composition wherein the stem cells are cultured as a monolayer, as required by Claim 10.
Kapalczynska et al. teaches that cell are cultured in either 2D or 3D when the cells are adherent, and in 2D adherent cultures cells grow as a monolayer (Pg. 911, Column 1, Lines 15-22 and 26-28 and Fig. 1A).
It would have been obvious to those of ordinary skill in the art to modify the composition of Li et al. and Fischer et al. which comprises stem cells cultured on the polymer scaffold which may be a sheet/film (therefore 2D) to culture the stem cells as a monolayer as taught by Kapalczynska et al. because there are only a finite number of ways to culture adherent cells, either as a 2D monolayer or in 3D. Those of ordinary skill in the art would have been motivated to make this modification because Li et al. teaches a composition which comprises stem cells on (thus adherent) the polymer scaffold sheet/film and Kapalczynska et al. teaches that adherent cells may be cultured as a 2D monolayer. There would have been a reasonable expectation of success in making this modification because Li et al. is drawn to adherent stem cells cultured on a 2D sheet/film polymer scaffold and Kapalczynska et al. teaches that adherent cells grown in 2D form a monolayer.
Claims 1, 5, 7, 9, 11, 12, 13 and 29 are rejected under 35 U.S.C. § 103 as
being unpatentable over Li et al. (WO 2007/090102 A2), cited in the IDS, in view of
Fischer et al. (2012), of record, as applied to Claims 1, 5, 7, 9, 11 and 12 above, and further in view of Chan et al. (US 2017/0360838 A1), of record, as necessitated by Applicant’s amendments to the claims filed 10/10/2025.
The teachings of Li et al. and Fischer et al. were discussed above.
Li et al. did not teach a composition wherein the stem cells are human skeletal
stem cells, as required by Claim 13;
or wherein the Wnt protein is Wnt3a, as required by Claim 29.
Chan et al. teaches a method for regenerating cartilage or bone, comprising
administering to an individual an effective dose of a skeletal stem cell (Pg. 39, Claim 1);
wherein the stem cell is human (Pg. 39, Claim 3);
and wherein an effective dose of the Wnt agonist Wnt3a is administered to
induce an osteogenic fate in the stem cells (Pg. 39, Claims 18, 20 and 22).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the composition of Li et al. which comprises one or more Wnt molecule(s) directly or indirectly covalently attached/conjugated to the polymer scaffold and stem cells to use human skeletal stem cells and Wnt3a as taught by Chan et al. because the composition of Li et al. is not limited to any particular Wnt or stem cell type and human skeletal stem cells and Wnt8a are disclosed in the prior art as specific stem cells and Wnt proteins suitable for use in methods/compositions for cartilage/bone regeneration . Those of ordinary skill in the art would have been motivated to make this modification because the composition of Li et al. is drawn to any stem cell and Wnt protein generically and Chan et al. teaches a specific stem cell type and Wnt protein for a particular application.
There would have been a reasonable expectation of success in making this modification because Li et al. is drawn to a composition comprising any stem cell type and Wnt and Chan et al. is drawn to a specific stem cell type and Wnt protein.
Response to Arguments
Applicant’s arguments, see Remarks, filed 10/10/2025, with respect to the above withdrawn objection/rejection have been fully considered and are persuasive.
Applicant's arguments filed 10/10/2025 have been fully considered but they are not persuasive.
The Applicant argues Li discloses a molecule covalently attached to the polymer scaffold which is capable of attaching to a differentiation factor but allegedly does not disclose that the molecule is the differentiation factor. Applicant asserts that the “molecule” and “differentiation factor” are two different components of the composition of Li, citing Fig. 12C (Remarks, Pg. 8, Lines 14-21 and Pg. 9, Lines 1-5).
This is not found to be persuasive for the following reasons, the teachings set forth at Pg. 73, Claim 18 state “further comprising a molecule which is covalently attached…directly to said first fibrous polymer scaffold, and said molecule is capable of covalently attaching to a differentiation factor” and “wherein the differentiation factor is Wnt” (therefore encompassing all/one or more Wnt proteins) (Pg. 74, Claim 23). The instant claims only require that the one or more Wnt proteins (differentiation factors) are “covalently conjugated to the scaffold”. There is nothing in the instant claims which requires that the Wnt proteins be directly conjugated to the scaffold without a linker. Thus, the prior art which covalently conjugates a Wnt protein to a scaffold with a covalently conjugated linker anticipates the claim.
The Applicant argues while Li mentions Wnt as a possible member attached to the linker in a list of possibilities but does not guide, direct or provide a reason to select Wnt. Applicant asserts that the reference provides no data that Wnt could be successfully conjugated and would function as claimed (Remarks, Pg. 9, Lines 6-18).
This is not found to be persuasive for the following reasons, the Li reference discloses an embodiment with Wnt as a possible member which can be covalently conjugated to a scaffold through a linker. Thus, the claimed subject matter is anticipated. See the MPEP at 2131 which states:
"When a claim covers several structures or compositions, either generically or as alternatives, the claim is deemed anticipated if any of the structures or compositions within the scope of the claim is known in the prior art." Brown v. 3M, 265 F.3d 1349, 1351, 60 USPQ2d 1375, 1376 (Fed. Cir. 2001)
As to the alleged lack of operability and lack of data showing operability, the anticipating reference is presumed to be operable and proof of efficacy is not required to anticipate. See the MPEP at 2121, I and III. The Examiner notes that the instant claims are directed to a composition and not to its method of use. Therefore, the ordinary artisan would expect that the anticipating composition of Li et al. would also have the same properties and characteristics as the claimed composition, when in use.
The Applicant argues that Li discloses a scaffold that is coated with gelatin or fibronectin while the instant claims do not require such coatings which would interfere with the conjugated Wnt proteins. Applicant further opines that while Li mentions “a stem or progenitor cell” stem cells are not found in nerve tissue and use of the composition as claimed would not be necessary (Remarks, Pg. 11, Lines 1-22).
This is not found to be persuasive for the following reasons, nowhere in the Examiner cited portions of Li is it stated that a scaffold coated with gelatin or fibronectin or only nerve tissue must be used. Thus, the reference anticipates for reasoning of record set forth above and in the prior action.
The Applicant argues that the ordinary artisan would not have been motivated to combine or modify Li with Morgan because Morgan is drawn to the use of Wnt proteins for a different purpose and does not teach or suggest the claimed Wnt protein composition (Remarks, Pg. 11, Lines 30-31 and Pg. 12, Lines 1-12).
This is not found to be persuasive for the following reasons, in response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As discussed above, Li anticipates the claimed composition. Morgan was cited only for its
teachings that Wnt3 and Wnt3a are Wnt proteins and thus it would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Li which comprises a Wnt molecule directly covalently attached/conjugated or indirectly covalently attached/immobilized to the polymer scaffold by a linker to use either Wnt3 or Wnt3a as taught by Morgan et a/. because the composition of Li is not limited to any particular Wnt and Wnt3 and Wnt8a are disclosed in the prior art as Wnt molecules. That Morgan utilizes Wnt proteins for a different purpose than Li is not relevant to the rationale for modifying Li as set forth above and in the prior action.
The Applicant argues that Lowndes is drawn to functionalizing specific surfaces for Wnt immobilization using EDC and NHS to convert surface carboxylic groups to succinimide ester that can form an amide (covalent) bond with Wnt. Applicant notes that the reference has an embodiment wherein Wnt was bound to glass, and suggests there would not be a reasonable expectation of success in using glass for the biocompatible polymer film because stem cells would not react to the substrates in the same way and Wnt would not function in the same way (Remarks, Pg. 12, Lines 14-31 and Pg. 13, Lines 1-25).
This is not found to be persuasive for the following reasons, in response to Applicant's arguments against the Lowndes references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this instance, Li already teaches the conjugation of Wnt proteins to a biocompatible polymer film. Lowndes was cited only for its teaching that substrates (not limited to glass) can be functionalized for Wnt immobilization and provides teaching on doing so. There would have been a reasonable expectation of success in modifying Li in view of Lowndes because Li is drawn to any covalent Wnt protein immobilization method and Lowndes is drawn to a specific Wnt protein immobilization method. The ordinary artisan would expect that stem cells would react to the biocompatible polymer film with covalently conjugated Wnt of Li in the same way regardless of the mechanism used to achieve the covalent bond.
The Applicant opines that biological systems are “complex” and “unpredictable” and alleges the ordinary artisan would not have reasonably expected that adding a feature from one system to another would result in a functional system. Applicant asserts that while Fisher discloses synthetic or collagen gels over an Extracellular matrix the reference does not teach or suggest that such an arrangement would work with stem cells that overly Wnt covalently conjugated to a functionalized biocompatible polymer as claimed (Remarks, Pg. 14, Lines 10-24).
This is not found to be persuasive for the following reasons, the Applicant’s assertions are wholly unsupported by any evidence on the record. See the MPEP at 2145, I. The Examiner has provided sound logical rationale in the prior action and above as to why the ordinary artisan would find obvious the modification of Li in view of Fischer. That is, it would have been obvious to those of ordinary skill in the art to modify the composition of Li which comprises stem cells which may be in a growth
environment (e.g. cultured) on the polymer scaffold which may be a sheet/film (therefore
2D) to overlay the cells with collagen as taught by Fischer because this would
provide a culture environment closer to the native 3D environment and benefits over
culturing in a planar 2D environment. Those of ordinary skill in the art would have been
motivated to make this modification in order to achieve the effects of altered cell
morphology and migration, as well as cytoskeletal organization and dynamics which are
more closely associated with native 3D conditions.
There would have been a reasonable expectation of success in making this modification because both Li and Fisher are generally drawn to the same field of endeavor, that is, cell culturing.
The Applicant argues that Kapalczynska is drawn to 2D monolayer cell culture and it cannot be predicted how stem cells will respond to different substrates. Applicant asserts that the reference is a general review of 2D and 3D cancer cell culture systems and a finding that “3D cultures can better mimic tissue” is only in a cancer cell not stem cell context (Remarks, Pg. 14, Lines 27-31 and Pg. 15, Lines 1-13).
This is not found to be persuasive for the following reasons, the Applicant’s assertions are wholly unsupported by any evidence on the record. See the MPEP at 2145, I. The Examiner has provided sound logical rationale in the prior action and above as to why the ordinary artisan would find obvious the modification of Li in view of Kapalczynska, that is, it would have been obvious to those of ordinary skill in the art to modify the composition of Li and Fischer which comprises stem cells cultured on the
polymer scaffold which may be a sheet/film (therefore 2D) to culture the stem cells as a
monolayer as taught by Kapalczynska because there are only a finite number of ways to culture adherent cells, either as a 2D monolayer or in 3D.
The Applicant argues that Chan is limited to the detection and characterization platforms and not to the generation of a transplantable osteogenic construct. Applicant argues that the teachings of Li, Fischer and Chan would not have motivated the ordinary artisan to combine the references with a reasonable expectation of success to arrive at the claimed invention (Remarks, Pg. 15, Lines 27-31 and Pg. 16, Lines 1-8).
This is not found to be persuasive for the following reasons, in response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which Applicant relies (i.e., a transplantable osteogenic construct) are not recited in the rejected claim(s). In any event, even if such a limitation was in the instant claims it would appear to be a non-limiting intended use of the claimed composition. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Chan was cited only for its use of human skeletal stem cells and the use of Wnt3a to induce osteogenic fate in the stem cells. The Examiner has provided sound logical rationale both above and in the prior action as to why the ordinary artisan in possession of the cited prior art references would find the claimed invention obvious and have a reasonable expectation of success in combining and/or modifying the cited prior art.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653