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 .
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 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.
DETAILED ACTION
Status of claims
The amendment filed on 07/17/2025 is acknowledged. Claims 2, 4, 12, and 13 have been canceled and claims 9-11, 14, and 15 have been withdrawn. Claims 1, 3, 5-8, and 16-19 are under examination in the instant office action.
Rejections withdrawn
Applicant’s amendments and arguments filed on 07/17/2025 are acknowledged and have been fully considered. Any rejection and/or objection not specifically addressed below is herein withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Rejections maintained
The following rejection of the claims is remained for reasons of record and the following.
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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3, 5-8, and 16-19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Bouhadir et al. (US 2004/0028745 A1) as evidenced by Mooney et al. (WO 1998012228 A1).
Bouhadir et al. teach a carrier/drug compound comprising an oxidized alginate polymer containing aldehyde groups which is crosslinked (claims 1-3) by a crosslinking compound having two or more hydrazide groups such as adipic dihydrazide (
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, the claimed hydrazide of formula III with p=4 in the instant claims 1 and 5) (paragraph 11 and claim 15);
wherein the oxidized alginate is an alginate which is oxidized so that 5-50% corresponding to the equivalent% of periodate used (1:1 ratio) (paragraph 9, i.e., potential crosslinking of 5-50% based on the available aldehyde groups on the alginate (example 22) and;
wherein the oxidized alginate polymer has a molecular weight (MW) of ≤300,000 daltons and is optionally lowered (paragraph 11);
wherein 5% oxidized alginate has a MW of 147 kDa (table 2).
Bouhadir et al. teach PCT/US97/16890 (Mooney et al., WO 1998012228 A1) being incorporated by reference as a whole (paragraph 5). According to Mooney et al. alginate polymer being oxidized therefor containing aldehyde groups, followed by being crosslinked and the crosslinked oxidized alginate polymer being used for human cell transplantation (the instant claim 8) (abstract, paragraph bridges page 3 and 4, and claim 13) and crosslinkers including diamine crosslinker such as diamino alkanes and dihydrazide crosslinker such as adipic dihydrazide (page 18, line 4-14).
With respect to the art rejection above, it is noted that the reference does not teach that the composition is capable of being used in the manner instantly claimed, [3D printable and injectable in the instant claim 1, bioprintable in the instant claim 18, and suitable for injection into tissue or bioprinted using a 3D printer in the instant claim 19]; please note that the claim element that uses capable of-type language does not impose any requirement that the device or composition actually perform the function. A claim that uses “capable of”-type language covers devices/compositions that have the recited components and which are capable of performing the recited functions. MPEP 2114.IV.
Bouhadir et al. do not expressly teach the property of a crossover point 100-400% shear strain in the instant claim 19. The claimed crossover point 100-400% shear strain is the property of 15% oxidized alginate crosslinked with a single crosslinker adipic dihydrazide (figure 2b in the instant specification of hydrazone: the table on page 20 and page 23 line 1-22). As a result of the hydrogel taught by Bouhadir et al. being the same oxidized alginate polymer (5-50% oxidation being obvious to 15% oxidation of the example in figure 2b) being crosslinked with the same single crosslinker adipic dihydrazide as in figure 2b, the hydrogel taught by Bouhadir et al. would necessarily have the claimed property, whether expressly recognized by Bouhadir et al. or not. Please refer to MPEP 2112.01.II:
A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Bouhadir et al. do not specify the same oxidation level and the subsequent crosslinking level as claimed in the instant claims 6, 7, 16, and 17.
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition overlaps with or lie inside the range disclosed in the prior art, such as in the instant rejection.
The claimed ranges of oxidation level and the subsequent crosslinking level are 2-20% and 5-15% and the range of oxidation level and the subsequent crosslinking level taught in the prior art is 5-50% and therefor, overlaps with or includes the claimed ranges.
Bouhadir et al. do not teach the diamine crosslinker such as diamino alkanes including O,O′-1,3-Propanediylbis-hydroxylamine (the claimed formula I in the instant claims 1 and 5) as the additional crosslinker besides adipic dihydrazide.
This deficiency is cured by Karlsson et al. who teach both adipic dihydrazide and diamine crosslinkers including O,O′-1,3-Propanediylbis-hydroxylamine are suitable crosslinkers (abstract and paragraph 37).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to modify the crosslinker taught by Bouhadir et al. and add O,O′-1,3-Propanediylbis-hydroxylamine taught by Karlsson et al. as an additional crosslinker. It is generally considered to be prima facie obvious to combine compounds each of which is taught by the prior art to be useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for combining them flows from both having been used individually in the prior art, and from them being recognized in the prior art as useful for the same purpose.
Response to Applicants’ arguments:
Applicants argue that the cited passages on page 18, line 4-14 of Mooney et al. (WO 1998012228 A1, incorporated by reference by Bouhadir et al.) teach crosslinking via carboxylic acid or alcohol groups of polysaccharides rather than aldehyde groups taught by Bouhadir et al.
However, this argument is not deemed persuasive.
First, Mooney et al., as an evidentiary reference, provide the disclosure of crosslinked oxidized alginate polymer being used for human cell transplantation to meet the limitation of the instant claim 8.
Second, Mooney et al. disclose crosslinking via carboxylic acid or alcohol groups of alginate or modified groups therefrom on page 18, line 6 and adipic acid dihydrazide crosslinking oxidized alginate with the oxidation results in polyaldehyde alginates on page 22, line 11-13). Thus Mooney et al. disclose adipic acid dihydrazide crosslinking oxidized alginate via aldehyde groups on alginate which is consistent with Bouhadir et al.’s teachings.
Applicants argue that Karlsson et al. teach grafting oxidized dextran onto hyaluronic acid via a reaction at the reduced end and through carboxylic groups (P35-37) for permanent covalent polymer modification, not for hydrogel formation and thus is fundamentally different class of material
However, this argument is not deemed persuasive. As stated in the rejection above and in the previous office action, Karlsson et al. provide teachings of both adipic dihydrazide and diamine crosslinkers are suitable crosslinkers (which is also supported by Mooney et al. on page 18, line 4-4) while diamine crosslinkers includes O,O′-1,3-Propanediylbis-hydroxylamine. Please refer to MPEP 2145.III:
the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
As stated in the response to applicants’ 37 CFR 1.132 declaration in the previous office action (modified based on the amendments), the evidence of surprising benefits of using a combination of crosslinkers in exhibition A does appear to have the benefit of controlled stiffness, stress relaxation, and self-healing as a result of a combination of adipic dihydrazide and O,O′-1,3-Propanediylbis-hydroxylamine, two specific compounds, as crosslinkers; however, the scope of the instant claim 1 is much broader, with regard to the combination of crosslinkers, than the scope of the combination of adipic dihydrazide and O,O′-1,3-propanediylbis-hydroxylamine: the scope of the instant claim 1 is not limited to the two specific compounds, but rather with m and p being 2-12 and with one or more carbon atoms in
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being optionally replaced by a heteroatom selected from O, S, and N. There is no adequate basis for reasonably concluding that the great number and variety of compositions included by the claims would behave in the same manner as the single tested composition. In other words, Applicant has not shown that based on this single example, it is reasonable to expect that other embodiments falling within the scope of the claims will behave similarly.
MPEP 716.02(b) III.: Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 extension fee 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 HONG YU whose telephone number is (571)270-1328. The examiner can normally be reached on 9 am - 5:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached on 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HONG YU/
Primary Examiner, Art Unit 1614