DETAILED ACTION
Receipt is acknowledged of applicant’s Response to Restriction Requirement and Amendment filed 12/2/2025.
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 .
Status of the Claims
Claims 50, 56, 58, 59 and 65 have been amended. Claims 1-49 are cancelled. No claims are newly added. Accordingly, claims 50-68 remain pending in the application.
Election/Restrictions
Applicant's election with traverse of Group I (claims 50-57 and 65-68) in the reply filed on 12/2/2025 is acknowledged. The traversal is on the ground(s) that the cited art does not teach the common technical feature, that is, claimed composition as amended and, as such, makes a contribution over the art. Thereby asserting that unity of invention exists. See pages 2-7 of Response to Restriction Requirement dated 12/2/2025. This is not found persuasive because the claimed composition as amended (the common technical feature amongst Groups I and II) does not make a contribution over the art as evidenced by the rejection of claim 50 under 35 USC 103 over Millan, Kopecek, Michal and Bernkop-Schnürch below. Since the composition is taught by the prior art, the composition cannot serve as a special technical feature, and further cannot serve as a single general inventive concept linking the different inventions of the present application. Thus, the application lacks unity of invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 58-64 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Accordingly, claims 50-57 and 65-68 are currently under examination.
Information Disclosure Statements
The IDS’s dated 7/31/2023, 8/5/2025 and 12/2/2025 have been considered. Signed copies are enclosed herewith.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 57 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
37 CFR §1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application".
There is no explicit or implicit teaching in the specification for “wherein the composition is injected int a tissue void and solidified”; the subject matter was not properly described as filed. The instant specification described injecting the scaffold material into a damaged area (e.g., page 2, lines 9-11; Example 4); however, there is no mention of subsequent solidifying, hardening, or the like. It is also noted that claim 57 was added as a preliminary amendment after the filing of the application and is not an original claim. Applicant is invited to identify the portion of the specification that teaches said limitation, as the examiner has not been able to locate the applicable disclosure. The claims within this rejection are examined as written by the applicant; at this time new matter must be considered as part of the claimed subject matter.
MPEP 2163.06 notes: "If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981)." MPEP 2163.02 teaches that "Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes "When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not "new matter" is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure".
This is a new matter rejection. Correction is respectfully requested.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 52 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 52 recites, “wherein the thiol-functionalized polymers having a percentage of their functional groups replaced with thiols, wherein the percentage of replacement is selected from the group consisting of 0-15%...”. The claim sets out that the polymers are thiol-functionalized, but also allows for 0% thiol replacement. Thus, the claim limitations contradict one another. The claims is indefinite because it is unclear whether the polymers require thiol functionalization.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 52 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 52 recites, “wherein the thiol-functionalized polymers having a percentage of their functional groups replaced with thiols, wherein the percentage of replacement is selected from the group consisting of 0-15%...”. Claim 52 depends from claim 50. Claim 50 sets out a composition comprising thiol-functionalized polymers. Claim 52 attempts to broaden the subject matter of claim 50 because the limitation, “wherein the thiol-functionalized polymers having a percentage of their functional groups replaced with thiols, wherein the percentage of replacement is selected from the group consisting of 0-15%...” allows for an embodiment that does not contain polymers that are thiol-functionalized (i.e., 0% thiol functionalization).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 50, 51, 53-56 and 65-68 are rejected under 35 U.S.C. 103 as being unpatentable over Millan et al. (WO 2014/032748 A1, March 6, 2014, hereafter as “Millan”) in view of Kopecek et al. (USPN 7,179,487 B1, Feb. 20, 2007, hereafter as “Kopecek”), Michal (US 2006/0233850 A1, Oct. 19, 2006, hereafter as “Michal”, and Bernkop-Schnürch et al. (“Development of controlled drug release systems based on thiolated polymers”, Journal of Controlled Release, Vol. 66, Iss. 1, May 2000, pp. 39-48; hereafter as “Bernkop-Schnürch”).
The instant claims are drawn to a composition comprising tissue extracellular matrix particles from biological tissues in combination with thiol-functionalized polymers, wherein the thiol groups on the thiol-functionalized polymers are adapted to cross-link directly to cysteine residues on the tissue extracellular matrix particles via disulfide bonding thereby forming a biocompatible scaffold.
Regarding instant claims 50, 51, 54 and 65-67, Millan teaches a method of cartilage repair comprising locally administering to the damaged cartilage a crosslinkable scaffold material, the scaffold material comprising at least one cytocompatible polymer and at least one of minced (particulate) tissue and cells, the crosslinking being provided by spontaneous reaction of complementary reactive groups of two types, at least one of these types being present on at least one of the cytocompatible copolymer, minced tissue, cells and cartilage surface (abstract; claim 1). Millan teaches that suitable complementary groups include those that result in disulfide bond formation (page 4, lines 27-29; claim 12). Millan also teaches that the tissue can be decellularized to remove epitopes which can cause acute inflammatory responses and pathogens and that said decellularization results in a scaffold of extracellular matrix ideally suited for regenerating injured or diseased tissue since it retains the high resolution and biological cues necessary for recapitulation of function (paragraph bridging pages 1-2; page 3, lines 29-30). Millan teaches the cytocompatible polymers can natively include reactive groups or can modified to include such groups which is “within the skill of the art” (page 2, lines 22-27). Said polymers include natural polymers such as collagen, gelatin and hyaluronic acid as well as synthetic polymers such as polyethylene glycol (page 2, line 29 – page 3, line 2; instant claims 51 and 65). Millan teaches that suitable minced tissue include the particular tissues, cartilage, liver and muscle (page 3, lines 20-24; instant claims 54 and 66).
While Millan teaches that polymers can be modified to include reactive groups as well as reactive groups that result in disulfide bond formation, Millan is silent to thiol functional groups.
Kopecek teaches hydrogels for biomaterial applications (page 1, lines 25-45). Kopecek teaches that polymer strands and protein domains can be modified to provide for covalent attachment and specifically teaches that polymer strands can be modified to contain thiol groups that can form disulfide bonds with the thiol group of cysteine residues (col. 5, lines 56-60).
Michal teaches bioscaffoldings formed from hydrogels such as hyaluronan or collagen (abstract). Michal teaches functionalizing said hydrogels with thiol groups ([0013], [0042], [0045] and [0046]).
The references are all drawn to polymers being modified to include reactive groups, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include thiol-functionalized polymers such as thiolated hyaluronan or thiolated collagen in Millan as suggested by Kopecek/Michal with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Millan generically teaches polymers such as hyaluronan and collagen can be modified to include reactive groups and said reactive groups can form disulfide bonds, Kopecek teaches more specifically modifying polymers to contain thiol groups to form disulfide bonds with cysteine residues, and Michal teaches the specific thiol-functionalized polymers, thiol-hyaluronan and thiol-collagen. A skilled artisan would have reasonably expected that modifying the cytocompatible polymers of Millan (e.g., hyaluronan or collagen) with thiol functional groups would provide reactive sites that would enable disulfide bonding.
While Millan teaches that minced tissue (extracellular matrix particles) can provide crosslinking by spontaneous reaction of complementary reactive groups of two types as well as reactive groups that result in disulfide bond formation, Millan is also silent to crosslinking directly to cysteine residues on the tissue (e..g, cartilage) extracellular matrix particles.
Bernkop-Schnürch teaches modifying polymers using cysteine resulting in thiolated polymers that are then able to form disulfide bonds with one another (abstract).
MPEP 2143 states,
The Federal Circuit in Perfect Web also discussed the role of common sense in the determination of obviousness. The district court had cited KSR for the proposition that "[a] person of ordinary skill is also a person of ordinary creativity, not an automaton," and found that "the final step [of the claimed invention] is merely the logical result of common sense application of the maxim ‘try, try again.’"
The references are all drawn to polymers being modified to include reactive groups, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include crosslinking directly to cysteine residues on the tissue extracellular matrix particles of Millan as suggested by Bernkop-Schnürch with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Millan generally teaches that minced tissue (extracellular matrix particles) can provide crosslinking by spontaneous reaction of complementary reactive groups of two types as well as reactive groups that result in disulfide bond formation and Bernkop-Schnürch specifically teaches using cysteine to enable formation of disulfide bonds. One of ordinary skill in the art would have reasonably expected that the naturally occurring cysteine found in tissue (e.g., cartilage) extracellular matrix would provide crosslinking by spontaneous reaction with a thiol such as the thiolated polymers of Millan/Kopecek/Michal to form disulfide bonds.
Regarding instant claims 55 and 68, the references teach the elements discussed above. Millan also teaches that the minced tissue can be of any suitable size, in particular, from 5 microns to 1 cm (page 3, lines 17-18). While Millan is silent to the particular ranges of less than about 100 microns, 100-125 microns, 250-500 microns, the claimed ranges lie inside the range disclosed by the prior art. MPEP 2144.05 states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”. It would have been prima facie obvious before the filing date of the claimed invention to optimize the sizing of the tissue taught in Millan by routine experimentation with a reasonable expectation of success. A skilled artisan would have been motivated to do so because the prior art teach the general conditions of the claim and it is not inventive to discover the optimum or workable ranges via routine experimentation.
Regarding instant claim 53, the references teach the elements discussed above. Millan also teaches that the implantable scaffold material can be designed to precisely mimic the structure of actual tissue (page 8, lines 4-6). Millan also teaches that the tissue is autologous, allogenic or xenogenic native tissue which already contains tissue-specific extracellular matrix components in physiologically accurate proportions (page 8, lines 22-25).
Regarding instant claim 56, the references teach the elements discussed above. Millan teaches that the tissue can be decellularized to remove epitopes which can cause acute inflammatory responses and pathogens (page 3, lines 29-30). Millan also teaches that the tissue can be lyophilized (page 7, line 24).
Thus, the combined teachings of Millan, Kopecek, Michal and Bernkop-Schnürch render the instant claims prima facie obvious.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Millan et al. (WO 2014/032748 A1, March 6, 2014, hereafter as “Millan”) in view of Kopecek et al. (USPN 7,179,487 B1, Feb. 20, 2007, hereafter as “Kopecek”), Michal (US 2006/0233850 A1, Oct. 19, 2006, hereafter as “Michal”, and Bernkop-Schnürch et al. (“Development of controlled drug release systems based on thiolated polymers”, Journal of Controlled Release, Vol. 66, Iss. 1, May 2000, pp. 39-48; hereafter as “Bernkop-Schnürch”), as applied to claim 50 above, and further in view of Duggan et al. (“Thiolated polymers as mucoadhesive drug delivery systems”, European Journal of Pharmaceutical Sciences, Vol. 100, March 2017, pp. 64–78; hereafter as “Duggan”).
The instant claims are described above.
Millan, Kopecek, Michal and Bernkop-Schnürch teach the elements discussed above.
Millan, Kopecek, Michal and Bernkop-Schnürch are silent to the percentage of thiol replacement being 0-15%, 15-30%, 30-60%, and combinations thereof.
Duggan teaches that the degree of intra- and intercrosslinking depends on the amount of free thiol moieties present on the polymer backbone; the more thiol groups attached, the more cohesive and adhesive the polymer (page 69, right col. 1st full para.). Duggan teaches that the crosslinking action of thiolation changes the degree of swelling of the polymer as well as changes the degradation pattern of the polymer (page 70, left col. 2nd para.).
The references are all drawn to polymers being modified to include reactive groups such as thiol groups, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the percentage of thiol replacement in the invention of Millan/Kopecek/Michal/Bernkop-Schnürch by way of routine experimentation as suggested by Duggan with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Duggan generally teaches that the degree of thiolation directly effects the degree of crosslinking of the polymer material which in turn alters the properties (e.g., degradation, swelling). One of ordinary skill in the art would have reasonably expected that optimizing the degree/percentage of thiolation by way of routine experimentation would allow for more reactive sites to form crosslinks/bonds (i.e., degree of crosslinking) and thereby allow for tuning of the properties of the polymer to the desired properties such as swelling or degradation rate.
Thus, the combined teachings of Millan, Kopecek, Michal, Bernkop-Schnürch and Duggan render the instant claim prima facie obvious.
Claim 57 is rejected under 35 U.S.C. 103 as being unpatentable over Millan et al. (WO 2014/032748 A1, March 6, 2014, hereafter as “Millan”) in view of Kopecek et al. (USPN 7,179,487 B1, Feb. 20, 2007, hereafter as “Kopecek”), Michal (US 2006/0233850 A1, Oct. 19, 2006, hereafter as “Michal”, and Bernkop-Schnürch et al. (“Development of controlled drug release systems based on thiolated polymers”, Journal of Controlled Release, Vol. 66, Iss. 1, May 2000, pp. 39-48; hereafter as “Bernkop-Schnürch”), as applied to claim 50 above, and further in view of KR 101650957 B1 (Aug. 24, 2016, hereafter as “KR ‘957”).
The instant claims are described above.
Millan, Kopecek, Michal and Bernkop-Schnürch teach the elements discussed above.
Millan, Kopecek, Michal and Bernkop-Schnürch are silent to a lubrication layer consisting essentially of hyaluronan deposited on a surface of the composition.
Regarding instant claim 57, it is noted that the limitation, “wherein the composition is injected and solidified...” is a process of using limitation and as such, determination of patentability is based on the product itself, not by the method of using. Furthermore, Millan teaches that the composition is injectable (page 9, line 6).
KR ‘957 teaches extracellular compositions for the repair or regeneration of damaged tissues such as cartilage (page 4, 1st paragraph). Said composition may be delivered as a scaffold (page 17, 2nd full para.). KR ‘957 teaches that hyaluronic acid is an excellent substrate that cartilage cells and other stromal cells are good for adhering, which can be incorporated as part of a scaffold or coated on a scaffold. (page 18, 4th paragraph).
Millan and KR ‘957 are drawn to compositions comprising extracellular matrix utilized as a scaffold for tissue repair, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a hyaluronic acid coating/layer on the surface of the scaffold of Millan/Kopecek/Michal/Bernkop-Schnürch as suggested by KR ‘957 with a reasonable expectation of success. A skilled artisan would have been motivated to do so because KR ‘957 teaches that a hyaluronic acid coating is an effective substrate for cartilage cells and other stromal cells to adhere to for the purpose of repairing or regenerating tissue such as cartilage tissue.
Thus, the combined teachings of Millan, Kopecek, Michal, Bernkop-Schnürch and KR ‘957 render the instant claim prima facie obvious.
Conclusion
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CASEY HAGOPIAN whose telephone number is (571)272-6097. The examiner can normally be reached on M-F 9:00 am - 5:00 pm.
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/CASEY S HAGOPIAN/Examiner, Art Unit 1617
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