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 .
Claim Status
Claims 1-4 and 7-20 are pending. Claims 1, 3-4, and 7-8 were amended, claims 5-6 were canceled, and no new claims were added in the reply filed 12/26/2025. Claims 2, 7, 9, 11-20 are withdrawn. Claims 1, 3-4, 8, and 10 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (products, original claims 1-10) and the species of Example 3 corresponding to a hydrogel comprising a modified fp-151 (SEQ ID NO: 9) conjugated to poly(meth)acrylic acid at available amides and comprising a modified fp-151 (SEQ ID NO: 9) conjugated to poly(meth)acrylic acid at available amides (see description, below) in the reply filed on 8/18/2025 is acknowledged.
The originally elected species is a product, and is understood to have the following structure: The species does not comprise the protein of fp-151 (SEQ ID NO: 9), which consists of the following sequence:
AKPSYPPTYKAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKPWSSEEYKGGYYPGNTYHYHSGGSYHGSGYHGGYKGKYYGKAKKYYYKYKNSGKYKYLKKARKYHRKGYKKYYGGGSSAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKAKPSYPPTYKL
Rather the originally elected species is a product-by-process, wherein the process requires modifying instant SEQ ID NO: 91, but unmodified SEQ ID NO: 9 is not actually present in the final product. The elected species is understood to comprise two distinct components:
First, 10 wt% of a modified SEQ ID NO: 9, wherein the tyrosines are converted to DOPA by an in vitro enzymatic reaction using mushroom tyrosinase (see, e.g., Spec. filed 3/11/2022 at ¶¶[00110]-[00111]), in combination with 1% acrylic acid N-hydrosuccinimide ester, 0.2 wt% α-ketoglutaric acid, 20 wt% acrylic acid, and water, cured into a hydrogel using a UV lamp (254 nm) (see, e.g., Spec. filed 3/11/2022 at ¶¶[00115]-[00116]),
Second, 0.1 wt% SEQ ID NO: 9 in PBS (pH 7.5), 2 mL methacrylic anhydride per 1 gram of SEQ ID NO: 9, reacted in a water bath to yield a modified SEQ ID NO: 9 comprising methacrylic groups; the sequence was then modified to convert tyrosines into DOPA. Then 10 wt% of the twice modified SEQ ID NO: 9 was added to 0.2 wt% α-ketoglutaric acid, 30 wt% methacrylic acid, and water, and cured into a hydrogel using a UV lamp (254 nm) (see, e.g., Spec. filed 3/11/2022 at ¶¶[00117]-[00118]).
Both components are added at a mass ratio of 1:1, and then cured again using a UV lamp (see, e.g., Spec. filed 3/11/2022 at ¶¶[00119]-[00120]) to yield the final, claimed product. The product-by-process limitations of the originally elected species are interpreted consistent with MPEP § 2113(I) for purposes of examination. The structure implied by these steps is not clarified on record, but is understood to be substantially as shown at instant Figures 1 and 2 as filed 3/11/2022, namely DOPA-substituted SEQ ID NO: 9 (Fp-151) crosslinked with polyacrylic acid combined 1:1 with DOPA-substituted SEQ ID NO: 9 (Fp-151) crosslinked with polymethacrylic acid (see, e.g., Figures 1-2 as filed 3/11/2022).
As filed 12/26/2025, the originally elected species is understood to read upon claim 1, 3-4, 8, and 10. However, the originally elected species does not read upon the following claims: It does not read upon claim 2 because, although the product-by-process steps do use SEQ ID NO: 9, the final product does not comprise SEQ ID NO: 9, which lacks DOPA residues (see Sequence Listing for SEQ ID NO: 9); it does not read upon claim 9 because the originally elected species is not identified as satisfying the functional limitations therein since it is not reasonably identified as “non-degradable in a dry state”, but rather the claimed product is understood to be a hydrogel capable of degradation via normal physical and chemical processes, and furthermore, “dry” and “wet” are relative terms; it does not read upon instantly amended claim 7 because the originally elected species is understood to include a mussel adhesive protein (i.e., SEQ ID NO: 9, a.k.a. Fp-151) at 10% by weight and 20 wt% acrylic acid, which is a 1:2 ratio that is outside the required 1:2.5-3.5 range, and further the originally elected species is not identified as reading upon amended claim 7. Accordingly, claims 2, 7, and 9 do not read upon the originally elected invention.
Following extensive search and examination, the originally elected species corresponding to the product-by-process description at Examples 1-3 (i.e., a dual network hydrogel combining the individual hydrogels shown at Figures 1-2) have been deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was previously extended to a non-elected species, namely the species taught by KR20190024721A (March 8, 2019), which was deemed anticipated and/or obvious (see, e.g., Action mailed 9/24/2025 at 5 and 12-17). In the Reply filed 12/26/2026, the pending claim scope was amended to exclude the hydrogels comprising fp-151 conjugated to polymethacrylic acid as taught by KR20190024721A, by requiring two separate components (i.e., “a first component” and a “second component”, forming what is understood to be a hybrid double crosslinked hydrogel) (see, e.g., claims filed 12/26/2025). Per MPEP § 803.02(III), Examination has now been extended to the non-elected species of a combination of two functionally equivalent MAP-polymers disclosed by JPH09225019A, where was subsequently deemed obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claims 11-20 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. Election was made without traverse in the reply filed on 8/18/2025.
Claims 2, 7, and 9 are 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 8/18/2025.
During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 1, 3-4, 8, and 10 are presently considered.
Priority
The priority claim to KR10-2021-0032773(filed 3/12/2021) and KR10-2022-0003448 (filed 1/10/2022) are each acknowledged.
Information Disclosure Statement
The IDS filed 12/30/2025 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 1 is representative of the pending claim scope, and was amended in the most recent reply to explicitly require two distinct components. Applicable claim interpretations are discussed below.
Regarding the preamble of claim 1 (“A bioadhesive composition”), per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claim 1 is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”).
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
The term “mussel adhesive protein” is broadly identified as a “protein derived from the mussel byssus” (see, e.g., Spec. filed 3/11/2022 at ¶[0054]) and then further exemplified (see, e.g., Spec. filed 3/11/2022 at ¶¶[0054]-[0059]).
Claim 1 recites “wherein the bioadhesive composition has a three-dimensional network structure”. All matter is understood to have a three-dimensional form involving a network of bonds, and therefore the “wherein” clause is understood to necessarily and inherently be satisfied by any hydrogel, film, tape, adhesive or bioadhesive taught in the prior art.
Additional claim interpretations are discussed below.
Withdrawn Claim Rejections
The rejection of claims 3-4 and 6-8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn in view of the amendments filed 12/26/2025.
The rejection of claim 5 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn as moot in view of the cancellation of claim 5.
The rejection of claims 1, 5, and 10 under 35 U.S.C. 102(a)(1) as being clearly anticipated by KR20190024721A (March 8, 2019) as evidenced by Machine Translation of KR20190024721A (Translated by Patent Translate Espacenet.org on 9/19/2025, 99 pages) is withdrawn in view of the amendments filed 12/26/2025.
The rejection of claims 1, 5, and 10 under 35 U.S.C. 103 as being unpatentable over KR20190024721A (March 8, 2019) as evidenced by Machine Translation of KR20190024721A (Translated by Patent Translate Espacenet.org on 9/19/2025, 99 pages) as applied to claims 1, 5, and 10 above, and further in view of US20110033548A1 (Feb. 10, 2011) is withdrawn in view of the amendments filed 12/26/2025.
The rejection of claims 1, 5-7, and 10 under 35 U.S.C. 103 as being unpatentable over KR20190024721A as evidenced by Trans’721 and in view of in view of US20110033548A1 as applied to claims 1 and 10 above, is withdrawn in view of the amendments filed 12/26/2025.
The rejection of claims 1, 5-7, and 10 under 35 U.S.C. 103 as being unpatentable over JPH09225019A (Sept. 2, 1997) as evidenced by Machine Translation of JPH09225019A (Translated by Patent Translate Espacenet.org on 9/19/2025, 35 pages) in view of Hermanson2 is withdrawn in view of the amendments filed 12/26/2025.
New Claim Rejections Necessitated by Applicant Amendment
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 1, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over KR20190024721A3 as evidenced by Machine Translation of KR20190024721A4 and in view of US20110033548A15.
Claim interpretation: The applicable claim interpretation has been set forth in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. The primary reference is not in English, and therefore all citations are made to the Machine Translation (Tran’721). Additional claim interpretations are set forth below.
KR20190024721A discloses and claims biomaterials comprising a mussel adhesive protein conjugated with a polymer (see, e.g., Tran’721 at claim 1), usable for tissue adhesion (see, e.g., Tran’721 at claim 6). Regarding instant claims 1, 10, and a bioadhesive composition comprising a mussel adhesive protein covalently linked to either polyacrylic acid or polymethacrylic acid via an amide bond, KR’472 discloses and claims compositions comprising any “temperature-sensitive polymer” (see, e.g., Tran’721 at claim 1, 7), in the form of a hydrogel (see, e.g., Tran’721 at claim 1, 5, 7), wherein the “temperature-sensitive polymer” is bound to the mussel adhesive protein via an amide bond (see, e.g., Tran’721 at claim 14), wherein the “temperature-sensitive polymer” may be “without limitation, a polymer of the polyacrylates system” (see, e.g., Tran’721 at ¶[0027], claim 26), wherein the mussel adhesive protein may be fp-151 (see, e.g., Tran’721 at claim 4), and wherein the biomaterial may be in the form of a hydrogel (see, e.g., Tran’721 at claim 5; compare id. with instant claim 10). Regarding instant claims 1, 8, 10, and a composition wherein the mussel adhesive protein is present at a mass ratio of 1:1 to 1:5 with either polyacrylic acid or polymethacrylic acid, KR20190024721A specifically exemplifies embodiments of conjugates identified as having 3:1, 2:1, 1:1 and 0.5:1 ratios of mussel adhesive protein and temperature-sensitive polymer (see, e.g., Trans’721 at ¶¶[0027], [0074]-[0075], [0131], [0136], Fig. 14). Notably, 0.5:1 may be written as 1:2, and therefore the prior art reasonably informs artisans that the mussel adhesive protein may be utilized at a ratio of at least 1:1 to 1:2, which is understood to overlap the claimed ratios of 1:1 to 1:5 as presently claimed (see, e.g., MPEP § 2144.05(I), explaining that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding the narrower range of claim 8, requiring 1:2.5-3.5, MPEP § 2144.05(I) explains that a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are “merely close”, such that an artisan would expect them to have the same properties7. Here, 1:2 and 1:2.5 are extremely close, wherein 1:2 corresponds to 33.33% of Component 1 and 66.67% of Component 2, and 1:2.5 corresponds to 28.57% of Component 1 and 71.43% of Component 2, which is less than 5% difference in each component (see also MPEP § 2144.06(II)(A), noting that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”).
The primary reference differs from the instantly claimed invention as follows: Although the prior art teaches hydrogels comprising single components comprising mussel adhesive protein conjugated to temperature-sensitive polymers at ratios of 1:1 to 1:2, the primary reference does not teach or direct artisans to combine two different species of components, each comprising mussel adhesive protein conjugated to temperature-sensitive polymers at ratios of 1:1 to 1:2, wherein the two different species of components are used within a ratio of 3:1 to 1:3 as presently claimed.
The primary reference directs artisans to use both polyacrylic acids and polymethacrylic acids: As noted above, KR20190024721A discloses and claims compositions comprising any “temperature-sensitive polymer” (see, e.g., Tran’721 at claim 1, 7, at ¶[0027]), in the form of a hydrogel (see, e.g., Tran’721 at claim 1, 5, 7), wherein the “temperature-sensitive polymer” is bound to the mussel adhesive protein via an amide bond (see, e.g., Tran’721 at claim 14). This is pertinent because KR’472 explicitly identifies that “temperature-sensitive polymers” includes “without limitation, a polymer of the polyacrylates system” (see, e.g., Tran’721 at ¶[0027]); an artisan would readily appreciate that “polyacrylates” included both polyacrylic acid and polymethacrylic acids (see, e.g., US20110033548A1 at ¶[0047], noting “polyacrylates (such as polyacrylic acid and polymethacrylic acid)”). Accordingly, in view of KR’721 and US’548, an artisan would readily appreciate that KR’472 directs artisans to make individual hydrogels comprising the individual components of a mussel adhesive protein conjugated at a 1:1 to 1:2 ratio of either the “temperature-sensitive polymer” of polyacrylic acid or polymethacrylic acids.
Regarding claims 1, 8, 10, and combinations of two equivalents known for the same purpose: Although the individual components (i.e., at instant claim 1, the “first” and “second” components) are understood to be separately disclosed in the art for use in hydrogels, as explained above, KR’721 does not teach a combination of both individual components. According, the remaining issue is whether or not it would be obvious to combine these two different “temperature-sensitive biomaterial[s] comprising a mussel adhesive protein to which a temperature-sensitive polymer is bonded”, usable for the same exact purposes (e.g., tissue regeneration, bonding tissues) (see, e.g., Tran’721 at ¶[0001], [0039]-[0040], claims 7-8), to create a combined temperature-sensitive biomaterial for the exact same purposes, at the ratios of 3:1 to 1:3 as claimed. Such a combination is obvious, because, per MPEP § 2144.06(I)
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
Accordingly, combining two species of “temperature-sensitive biomaterial[s] comprising a mussel adhesive protein to which a temperature-sensitive polymer is bonded” as taught by KR’721, each of which is taught by KR’721 to be useful for the same purpose (e.g., tissue regeneration, bonding tissues), in order to form a combined composition to be used for the very same purpose (e.g., tissue regeneration, bonding tissues) is prima facie obvious.
Regarding claims 1, 8, 10, and combinations of two functional equivalents known for the same purpose within the ratio of 3:1 to 1:3: In view of KR’721 an artisan would readily conclude the components at issue were functional equivalents (see discussion above), and therefore reasonably conclude that the specific ratio was not relevant or critical to the final properties of a combination of the functional equivalents, so long as the total combined amount of protein-polymers was within the range of 12 wt% to 55 wt% as taught by the prior art (see, e.g., Tran’721 at ¶¶[0037]-[0039], [0042], claim 9). So long as the total amount was within the range described by KR’721, regardless of the specific ratio of functional equivalents used, the resulting hydrogel would be predicted and expected to have the same art-recognized utility (e.g., tissue regeneration, bonding tissues). Accordingly, the difference in ratios of functional equivalents would not be considered to be of critical importance (see, e.g., MPEP § 2144.06(II)(A), noting that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”). Furthermore, upon review of the instant record, the claimed ratio appears to serve no clear purpose and does not clearly result in any unexpected advantage or result commensurate in scope with the requirements of MPEP § 716.02 (see, e.g., Spec. filed 11/03/2022 at ¶[0070]). Accordingly, since Applicant has not disclosed that the specific limitations recited in instant claims regarding the ratios of these two components are for any particular purpose or solve any stated problem and the prior art teaches that such components would be understood to be functional equivalents for the applications disclosed by the prior art (e.g., tissue regeneration, bonding tissues), and therefore could be utilized at any ratio so long as the total amount of the two equivalents utilized was within the range of 12 wt% to 55 wt% as taught by the prior art (see, e.g., Tran’721 at ¶¶[0037]-[0039], [0042], claim 9), wherein the total amount utilized is a result-effective variable impacting hydrogelation (see, e.g., Tran’721 at ¶¶[0051]), tissue adhesiveness (see, e.g., Tran’721 at ¶¶[0042]), and even phase transition temperature (see, e.g., Tran’721 at ¶¶[0075]). Accordingly, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the hydrogel arts.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): Per MPEP § 2144.06(I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." Similarly, in the instant case, it is prima facie obvious to combine two species of “temperature-sensitive biomaterial[s] comprising a mussel adhesive protein to which a temperature-sensitive polymer is bonded” as taught and suggested by KR’721 in view of US’548, wherein such compounds are taught for the same purpose (e.g., tissue regeneration, bonding tissues), in order to form a third, combined composition to be used for the very same purpose because the idea of combining them flows logically from their having been individually taught in the prior art. Furthermore, such combination would merely yield predicted and expected results, namely a hydrogel suitable for use as a bioadhesive in tissue regeneration, bonding tissues applications (see, e.g., MPEP § 2144.05(I)-(II); 2144.06(I); 2143(I)(A)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine a two functionally equivalent “temperature-sensitive biomaterial[s] comprising a mussel adhesive protein to which a temperature-sensitive polymer is bonded” known in the prior art to arrive at a composition comprising both functionally equivalent components useful for the same purpose taught and disclosed by the prior art.
Accordingly, claims 1, 8, and 10 are rejected.
Claims 1, 3-4, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over JPH09225019A8 as evidenced by Machine Translation of JPH09225019A9 in view of Hermanson10.
Claim interpretation: The applicable claim interpretation has been set forth in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. The primary reference is not in English, and therefore all citations are made to the Machine Translation (Tran’019). Additional claim interpretations are set forth below.
JPH09225019A pertains compositions suitable for use as biological tissue adhesives comprising an adhesive polypeptide and a water-soluble polymer see, e.g., Trans’019 at ¶¶[0001], [0018], claims 1, 3-4). Regarding instant claims 1, 3-4, 8, 10, and a bioadhesive composition comprising a mussel adhesive protein covalently linked to either polyacrylic acid or polymethacrylic acid, JPH09225019A pertains to a biological tissue adhesive comprising an adhesive polypeptide and a non-natural water-soluble polymer (see, e.g., Trans’019 at ¶[0001], claims 1, 3-4), wherein the non-natural water-soluble polymer may be either polyacrylic acid or polymethacrylic acid (see, e.g., Trans’019 at ¶[0001], [0009], [0015], claim 4), wherein the adhesive polypeptide may be a mussel adhesive protein (see, e.g., Trans’019 at ¶¶[0003], [0006], claim 1), wherein each tyrosine in the mussel adhesive protein may be converted to DOPA using a tyrosinase (see, e.g., Trans’019 at ¶¶[0006], [0013]-[0014]; compare id. with instant claims 3-4). Regarding instant claims 1, 3-4, 8, 10, and a composition wherein the mussel adhesive protein is present at a mass ratio of 1:1 to 1:5 with either polyacrylic acid or polymethacrylic acid, JPH’019 discloses and directs artisans to utilize a the adhesive polypeptide to the water-soluble polymer at a ratio of “1:0.5 or more” (see, e.g., Trans’019 at ¶[0007]), wherein “the composition ratio of adhesive polypeptide to water-soluble polymer is preferably in the range of 1:5 to 1:0.01” (see, e.g., Trans’019 at ¶[0016]). Accordingly, the prior art teaches and directs artisans to utilize adhesive polypeptide to the water-soluble polymer at an overlapping range of ratios (see, e.g., MPEP § 2144.05(I), explaining that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding instant claim 10 and the use of a hydrogel, an artisan would readily appreciate that JPH09225019A pertains to hydrogels because it discloses “curing” the composition, and identifies that the viscosity may be adjusted from at least 300 to 10,000 centipoise (see, e.g., Trans’019 at ¶¶[0016]-[0017], claim 1). Regarding instant claims 1, 3-4, 8, 10, and compositions wherein a mussel adhesive protein is covalently conjugated to either polyacrylic acid or polymethacrylic acid, JPH09225019A identifies that “the adhesive polypeptide may also be covalently fixed to the water-soluble polymer”, and directs artisans that such polymers have “reactive groups such as. . . carboxyl groups” and that the polypeptides have “amino groups” (see, e.g., Trans’019 at ¶[0017]).
The primary reference differs from the instantly claimed invention as follows: Although the primary reference directs artisans to make and use two individual species of tissue adhesives comprising a mussel adhesive protein covalently linked to either polyacrylic acid or polymethacrylic acid at ratios of 1:0.5 to 1:5, the primary reference differs from the amended claim scope as follows: First, the primary reference does not explicitly identify that the protein is covalently linked to the water-soluble polymer via an amide bond. Second, the primary reference does not teach or direct artisans to combine two different species of tissue adhesive compounds, each comprising mussel adhesive protein conjugated to a water-soluble polymer at ratios of 1:0.5 to 1:5, wherein the two different species of components are used within a ratio of 3:1 to 1:3 as presently claimed.
Regarding instant claim 1, 3-4, 8, 10, and linkage via an amide bond, the primary reference identifies that “the adhesive polypeptide may also be covalently fixed to the water-soluble polymer”, and directs artisans that such polymers have “reactive groups such as. . . carboxyl groups” and that the polypeptides have “amino groups” (see, e.g., Trans’019 at ¶[0017]). Accordingly, an artisan would review the art for known and common ways of conjugating -carboxylic acid (-COOH) moieties (i.e., functional groups present in polyacrylic acid and polymethacrylic acid) to amines present in mussel adhesive polypeptides, such as Hermanson, which pertains to bioconjugate techniques (see title, passim). Hermanson identifies that polypeptides may be modified at primary amines (see, e.g., Hermanson at Fig. 2.6 on 129, 129 at col II at final ¶). Hermanson shows that conjugating compounds to amine groups in polypeptide sequences was well-known and routine in the prior art (see, e.g., Hermanson at Table 3.1 at pages 230-232, Reaction 3.4 on 234). For example, Hermanson establishes that Carbodiimides may be utilized to conjugate carboxylate containing compounds to primary amines via an amide bond (see, e.g., Hermanson at 237 at col I-II at § 1.2, Reactions 3.11 and 3.12 on p. 237), which is understood to be applicable to polyacrylic acid (see id. at 237 at col II at final ¶). Hermanson explicitly addresses “poly(acrylic acid)” and “poly(methacrylic acid)” (see, e.g., Hermanson at 554 at col II at 1st full ¶, Fig. 14.6 on 558), and directly addresses general “Coupling to Carboxylate Particles” which involves the same chemistry at issue (see, e.g., Hermanson at 558 at col I-II at § “Coupling to Carboxylate Particles”). Hermanson identifies that polypeptides may be conjugated to carboxylate moieties (i.e., functional groups present in polyacrylic acid and polymethacrylic acid) by multiple means (see, e.g., Hermanson at Fig. 14.7 at 559). Accordingly, Hermanson establishes that it was well-within the ordinary skill in the art to covalently bond either polyacrylic acid and polymethacrylic acid to a mussel adhesive polypeptides exactly as taught by the primary reference by utilizing known chemical methodologies as taught by Hermanson.
Regarding claims 1, 3-4, 8, 10, and combinations of two functional equivalents known for the same purpose: The primary reference directs artisans to make and use individual species of tissue adhesives comprising a mussel adhesive protein covalently linked to either polyacrylic acid or polymethacrylic acid at ratios of 1:0.5 to 1:5 (see, e.g., Trans’019 at claims 1-4, see discussion above), but does not specifically teach or disclose a combination of two such adhesive compounds. Accordingly, the relevant issue is whether or not it would be obvious to combine two different “biological tissue adhesives” usable for the same exact purposes (e.g., as a tissue adhesive), to create a third composition for use in the exact same purpose, at the ratios of 3:1 to 1:3 as claimed. Such a combination is obvious, because, per MPEP § 2144.06(I)
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
Accordingly, combining two biological tissue adhesives (i.e., functional equivalents) together to form a third biological tissue adhesive useful for the exact same purpose (e.g., as a tissue adhesive), is prima facie obvious.
Regarding claims 1, 3-4, 8, 10, and combinations of two functional equivalents known for the same purpose within the ratio of 3:1 to 1:3: In view of the primary reference an artisan would readily conclude that the components at issue were functional equivalents (see discussion above), and therefore reasonably conclude that the specific ratio of functional equivalents was not relevant or critical to the final properties of a combination of the two functional equivalents. Furthermore, an artisan would recognize that so long as the total combined amount of protein-polymers was within the range of 5-50 wt%, that the “the optimum concentration is determined by the viscosity of the aqueous solution mixture”, wherein viscosity of the compound may be 100 to 50,000 centipoise (see, e.g., Trans’019 at ¶¶[0006], [0012], [0016], claims 1-4), and wherein the total combined amount and total amount of water-soluble polymer utilized are result-effective variables impacting viscosity (see, e.g., Trans’019 at ¶¶[0007], [0015], [0016], claims 1-4). Accordingly, an artisan would readily appreciate that the resulting compositions satisfying such limitations would result in functional biological tissue adhesives, and therefore the difference in ratios of two functionally equivalents components would not be considered to be of critical importance (see, e.g., MPEP § 2144.06(II)(A), noting that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”). Furthermore, upon review of the instant record, the claimed ratio appears to serve no clear purpose and does not clearly result in any unexpected advantage or result commensurate in scope with the requirements of MPEP § 716.02 (see, e.g., Spec. filed 11/03/2022 at ¶[0070]). Accordingly, since Applicant has not disclosed that the specific limitations recited in instant claims regarding the ratios of these two components are for any particular purpose or solve any stated problem and the prior art teaches that such components would be understood to be functional equivalents for the applications disclosed by the prior art, and therefore could be utilized at any ratio to predictably obtain a biological tissue adhesive so long as the total combined amount of protein-polymers was within the range of 5-50 wt% and viscosity was 100 to 50,000 centipoise. Accordingly, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the biological tissue adhesive arts.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): Per MPEP § 2144.06(I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." Similarly, in the instant case, it is prima facie obvious to combine two species of “biological tissue adhesives” usable for the same exact purposes (e.g., as a tissue adhesive), to create a third composition for use in the exact same purpose, as taught and suggested by the primary reference in view of Hermanson, because the idea of combining them flows logically from their having been individually taught in the prior art. Furthermore, such combination would merely yield predicted and expected results, namely a composition suitable for use as a “biological tissue adhesives (see, e.g., MPEP § 2144.05(I)-(II); 2144.06(I); 2143(I)(A)), wherein the individual components would merely perform the art-recognized function attributable to them in combination as they perform independently.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine a two functionally equivalent “biological tissue adhesives” known and taught by the prior art to arrive at combined composition comprising both functionally equivalent components useful for the same purpose taught as disclosed by the prior art.
Accordingly, claims 1, 3-4, 8, and 10 are rejected.
Response to Arguments
Applicant’s arguments filed 12/26/2025 have been fully considered but are substantially rendered moot in view of the new and revised grounds of rejection necessitated by Applicant’s amendments, as set forth above. Although these rejections relied upon art previously used on record, the rejections rely upon different rationales that directly address the limitations added in the amendments filed 12/26/2025 requiring two separate components. Applicable arguments are addressed below.
It is the Examiner’s understanding that Applicant addresses the prior rejections of record, which relied upon KR’721, Trans’721, US’548, JPH’019, Trans’019, and Hermanson at pages 8-11 (see, e.g., Reply filed 12/26/2025 at 8 at final ¶ to page 11 at 1st full ¶). It is the Examiner’s understanding that Applicant alleges that the amended claims now require “two different covalent conjugate components” at a “defined mixture ratio”, which was not addressed by the prior rejections of record (see, e.g., Reply filed 12/26/2025 at 8-9 at bridging ¶, 9 at 1st full ¶, 10-11 at bridging ¶). This is neither disputed nor dispositive of obviousness, because such limitations were not previously claimed and have necessitated the new rejections set forth above. Notably, the combination of two equivalent compounds to create a third compound for the same use is prima facie obvious per MPEP § 2144.06(I). Furthermore, the “defined mixture ratio” and “dual-component architecture” does not appear to address any need in the art or otherwise result in unexpected results that patentably distinguish the claimed invention relative to a combination of functionally equivalent components taught by the prior art (see, e.g., MPEP § 2144.05(I)-(II); 2144.06(I); 2143(I)(A)). No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date, and upon review of the instant record, the claimed ratio appears to serve no clear purpose and does not clearly result in any unexpected advantage or result commensurate in scope with the requirements of MPEP § 716.02 (see, e.g., Spec. filed 11/03/2022 at ¶[0070]). Accordingly, such arguments do not render the claim scope non-obvious in view of the art of record.
It is the Examiner’s understanding that Applicant addresses the prior rejections of record, which relied upon KR’721, Trans’721, US’548, JPH’019, Trans’019, and Hermanson at pages 8-11 (see, e.g., Reply filed 12/26/2025 at 8 at final ¶ to page 11 at 1st full ¶). It is the Examiner’s understanding that Applicant alleges that a “simple substitution” rationale does not address the amended invention (see, e.g., Reply filed 12/26/2025 at 8-9 at bridging ¶). This is neither disputed nor dispositive of obviousness, because such limitations were not previously claimed and have necessitated the new rejections set forth above.
It is the Examiner’s understanding that Applicant alleges that the ratio of 3:1 to 1:3 serves a purpose, namely that
The specification further explains that mixing the first and second components within a mass ratio of 3:1 to 1 :3 permits control of decomposition time in vivo, maximizes the mussel adhesive protein so that it is not crystallized, and prevents wasting protein.
(see, e.g., Reply filed 12/26/2025 at 9-10 at bridging ¶).
Applicant provides no supporting evidence for this claim. It is the Examiner’s understanding that Applicant may be referring to ¶[00103] of the Specification (see, e.g., Spec. filed 03/11/2022 at ¶[00103]), but Applicant’s summary does not appear to reflect the actual disclosure in context, because the disclosure merely acknowledges that “decomposition time may be adjusted during adhesion in the living body”, and that “mussel adhesive protein is maximized within the mixing ratio so that it is not crystallized”, wherein “mussel adhesive protein” is singular, not plural; wherein decomposition is actually tested showed that Example 2 performed better than Example 3 (see, e.g., Spec. filed 03/11/2022 at ¶[00115]-[00120], [00149]-[00151], Figure 5), which is critical because Example 2 is a single component composition excluded by amended claim 1, whereas Example 3 is a dual component compound reading on the instant claims. Accordingly, the evidence of record shows that the ratio is not pertinent to decomposition times, and no evidence of unexpected results regarding crystallization has been shown. Accordingly, upon review of the instant record, the claimed ratio appears to serve no clear purpose and does not clearly result in any unexpected advantage or result commensurate in scope with the requirements of MPEP § 716.02 (see, e.g., Spec. filed 11/03/2022 at ¶[0070]). Rather the evidence of record shows that such compounds result in bioadhesive compositions, exactly as would be predicted and expected in view of the prior art, which weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Accordingly, zero evidence of criticality of range commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
It is the Examiner’s understanding that Applicant alleges unexpected results (see, e.g., Reply filed 12/26/2025 at 10 at 1st full ¶). These data have been reviewed but not found persuasive to establish criticality of range or unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02. For example, no comparison of the closest existing prior art of record has been shown (see, e.g., MPEP § 716.02(e)) showing any practical or statistically significant difference (see, e.g., MPEP § 716.02(b)), and no evidence showing any data or results is commensurate in scope with the pending claims has been shown (see, e.g., MPEP § 716.02(d)). Therefore, such arguments are not persuasive because the requirements of MPEP §§ 716, 716.01, and 716.02 have not been satisfied.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 12/26/2025 at 10-11 at bridging ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Accordingly, all applicable arguments have been fully considered, but not found persuasive in view of the new rejections set forth above. The new rejections were necessitated by the Applicant’s amendments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 8962025 pertains to sealants and adhesives (see, e.g., id. at title, abs, claims).
US 9320826 pertain to biological tissue adhesives (see, e.g., id. at title, abs, claims).
US2018/0118978 pertains to catechol-containing adhesive hydrogels (see, e.g., id. at title, abs, claims).
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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 SEQ ID NO: 9 is identified as a prior art sequence (see, e.g., Spec. filed 3/11/2022 at ¶¶[00110]-[00113], identifying that fp-151 is SEQ ID NO: 9, and disclosed by Hwang et al.).
2 Hermanson, Bioconjugate Techniques. 3rd ed. London: Academic Press, 2013. Print, title page, pages 127-131, 229-234, 237, 549, 553-559; hereafter “Hermanson”
3 Cited in previous action.
4 Cited in previous action.
5 Cited in previous action.
6 Polymethacrylic acid is explicitly exemplified.
7 See also, In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%).
8 Cited in previous action.
9 Cited in previous action.
10 Hermanson, Bioconjugate Techniques. 3rd ed. London: Academic Press, 2013. Print, title page, pages 127-131, 229-234, 237, 549, 553-559; hereafter “Hermanson”; cited in previous action.