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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-7, in the reply filed on 5/29/26 is acknowledged. The traversal is on the ground(s) that the Examiner has failed to explain how the specific technical features of the present invention’s Groups I, II, and III fail to contribute over the cited reference of Ramshaw et al. (WO2015031950). This is not found persuasive because of the following reasons. From MPEP 1850(II): "The term “special technical features” is defined as meaning those technical features that define a contribution which each of the inventions considered as a whole, makes over the prior art....Whether or not any particular technical feature makes a “contribution” over the prior art, and therefore constitutes a “special technical feature,” should be considered with respect to novelty and inventive step." The Examiner has identified the special technical feature as the crosslinked sponge based on collagen-like protein and, as discussed on page 4 in the restriction requirement, the special technical feature of a crosslinked sponge based on collagen-like protein is known through the teachings of Ramshaw et al. Applicant has pointed to no error in the Examiner’s interpretation of the art of Ramshaw et al. Consequently, that technical feature cannot unify the inventions of Groups I-III.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/29/26.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/20/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
On page 6, line 2 of the specification, SEQ ID NO:5 to 12 is recited:
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However, only 9 SEQ ID Numbers have been provided and therefore it is unknown what SEQ ID NO:10-12 might be.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that SEQ ID NO:10-12 are not supported. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
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 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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Ramshaw et al. (US10155793) and Morita et al. (US5116552) as evidenced by Millipore Sigma ([online] retrieved on 6/10/26 from: https://www.sigmaaldrich.com/US/en/products/chemistry-and-biochemicals/biochemicals/biological-buffers/phosphate-buffer-saline; 1 page).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, 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.
Applicant claims:
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Claim interpretation: The term “collagen-like” is a term of the art and not indefinite. Please note that optional steps do not need to be performed. “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.” See M.P.E.P § 2111.04; see also MPEP §§ 2103(C) and 2173.05(h).
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a tissue engineering research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from the tissue engineering art including methods and materials for medical applications and scaffolds such as collagen and collagen based materials1 as well as bacterial collagen-like proteins2 and in the form of lyophilized chemically crosslinked sponges3— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 3 and 4, Ramshaw et al. teach modified bacterial collagen-like proteins (Abstract; title; claims 1-11), in the form of a sponge (column 11, lines 50-55; column 23, lines 4-6) and produced by a method of:
crosslinking a modified bacterial collagen solution using glutaraldehyde to provide a hydrogel, which reads on claimed steps i) and ii) by providing a solution comprising at least one collagen-like protein and crosslinking the at least one collagen-like protein with at least one cross-linker with an implicit incubation period to obtain a hydrogel;
that is then freeze-dried to form a sponge that is stable at > 37°C (Example 21, column 30, lines 45-57), which reads on lyophilization step iv).
Ramshaw et al. teach that the solutions of collagen are aqueous buffer systems (Examples 17-20). Regarding claim 6, Ramshaw et al. teach washing with phosphate buffered saline (PBS, which has a pH of 7-7.44)(Column 29, lines 5-6). Ramshaw et al. also teach adding additives: “Persons skilled in the art will be aware of certain agents or additives that may be added during the processing of the collagen-like protein which assist in maintaining the thermal stability of the triple-helical collagen-like protein.” (Column 15, lines 44-48).
Regarding claim 2, Ramshaw et al. teach using a 2 fold molar excess of crosslinking agent (Example 14) and a 5 fold excess of crosslinking agent (Example 15), thereby having the functional groups of the at least one collagen-like protein to the functional groups of the at least one cross-linker, which undergo a reaction with each other present in a ratio of 1:0.1 to 1:5. Ramshaw et al. also teach: “by increasing the extent of crosslinking, it is possible to generate hydrogels which have various uses in medical and non-medical applications, as well as cosmetic applications.” (Column 6, lines 50-53).
Regarding claim 6, Ramshaw et al. teach performing the crosslinking reactions at pH values of 6.8 (Example 13), 7.2 (Examples 11-12) and 8.0 (Example 14), thereby rendering obvious pH values to perform any washing away of excess crosslinking reagent.
Regarding claims 1-7, Morita et al. teach methods of crosslinking collagen 0.3 w/v%, which is equivalent to 3 mg/ml, with glutaraldehyde at 4° C for 24 hours, washed to remove excess glutaraldehyde and then rapidly frozen to -80° C or -135° C and dried by vacuum lyophilization (Column 4, lines 8-32). Morita et al. teach sterilization of the sponge (Column 3, lines 60-68). Morita et teach other useful crosslinking agents: “Examples of useful crosslinking agents are various and include conventional ones such as formaldehyde, hexamethylene diisocyanate, glutaraldehyde and the like.” (Column 2, lines 63-66). Morita et al. also teach: “Subsequently the atelocollagen solution is placed into a suit able mold, frozen and dried to give microporous sponge. The freezing and drying may be conducted under conventional conditions. The sponge is frozen at a low temperature of about -20° to about -50° C and vacuum-dried at a temperature of about -30° to about 40° C in a vacuum of about 0.01 to about 0.2 mmHg.” (Column 2, lines 42-50).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Ramshaw et al. is that Ramshaw et al. do not expressly teach the concentration of the bacterial collagen like protein is from 2.5 to 100 mg/ml or an incubation with glutaraldehyde crosslinking agent that is performed for 5 minutes to 48 hours and/or at 4 to 37 °C and that the lyophilization is performed at -40 to -60 °C; and/or the obtained hydro gel is cooled to -20 to -80 °C before the lyophilization is performed. However, not only is the concentration of the bacterial collagen like protein readily optimized by the ordinary artisan to obtain the desired sponge, but also the analogous art of Morita et al. teaches a concentration of collagen within the claimed range. From MPEP 2144.05 (II) (A): “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Thus, having from 2.5 to 100 mg/ml of the bacterial collagen-like protein in a ratio of 1:0.1 to 1:5 of the crosslinker is merely an optimization of the teachings of the combined references. Ramshaw et al. teach in a photo-crosslinking example, an incubation of at least 1 hour at 37° C (Column 21, lines 15-19) and Morita et al. teach an incubation at 4° C for 24 hours. It is then merely routine optimization to incubate the glutaraldehyde crosslinked example of Ramshaw et al. for 5 minutes to 48 hours and/or at 4-37°C with a reasonable expectation of success. Regarding the lyophilization limitations, Morita et al. provide guidance for the artisan to first freeze the hydrogel before lyophilization to about -20° to about -50° C, and preferably -80°C or lower, and Morita et al. teach lyophilization at a temperature of about -30° to about 40° C. Consequently, it is merely routine optimization of the lyophilization conditions where the lyophilization is performed at -40 to -60 °C; and/or the obtained hydrogel is cooled to -20 to -80 °C before the lyophilization is performed. The result is the same: a collagen-like sponge is obtained. Furthermore, the optional steps of adding an additive, washing the hydrogel and sterilizing are obvious over the combined references.
Claims 4 and 6 are further rejected under 35 U.S.C. 103 as being unpatentable over Ramshaw et al. (US10155793) and Morita et al. (US5116552) as applied to claims 1-7 above, in further view of Chuang et al. (Artif Cells Nanomed Biotechnol. 2018; 46(SUP3): S434–S447) and Harden et al. (WO2019046943) and Sarrigiannidis et al. (Materials Today Bio 2021;10:100098; 22 pages).
Applicant claims:
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The references of Ramshaw et al. and Morita et al. are discussed in detail above. The combined references do not expressly teach crosslinkers with two succinimidyl groups, DMTMM, transglutaminase, diisocyanate and the combination of EDC and NHS or employing a buffer selected from 2-[ 4-(2-hydroxyethyl)piperazin-l-yl]ethane-l-sulfonic acid buffer (HEPES) and 2-morpholin-4-ylethanesulfonic acid buffer (MES) for washing the hydrogel. However, Harden et al. guide the artisan to DMTMM in PBS and EDC/NHS in MES for use as crosslinking agents with collagen like polypeptides (Page 25, lines 13-16; page 29, lines 6-12; page 39, lines 20-28). Harden et al. also teach: “For example, by varying the molar equivalent ratio of a chemical crosslinker such as EDC or DMTMM to the lysine groups the user can tune the physical properties (e.g. tensile strength, modulus) of the crosslinked hydrogel.” (Page 25, lines 13-16). Chuang et al. teach using Dulbecco’s PBS, HEPES and MES in methods of physically crosslinking collagen hydrogels with EDC and NHS (Title; Abstract and Page 4, Self-assemble collagen hydrogel formation and Synthesis and characterization of collagen-phenolic (collagen-Ph) conjugates). The Examiner also notes that Morita et al. teach formaldehyde which has a MW of 30.03 g/ml. In addition, the art of Sarrigiannidis et al. guides the artisan to multi-arm PEG succinimidyl glutarate, glutaraldehyde, carbodiimide/hydroxysuccinimide ester, diisocyanate and transglutaminase for modifying hydrogels (Page 7, figure 3); Page 9 2.1.2. Chemical and enzymatic cross-linking through page 11, left column 2.1.2.7.). Consequently, it is merely judicious selection of conventional buffering agents such as HEPES and MES at a pH from 5.5 to 8.2 to wash the hydrogel and conventional crosslinking agents such as crosslinkers with two succinimidyl groups, DMTMM, transglutaminase, diisocyanate and the combination of EDC and NHS and formaldehyde by the ordinary artisan to employ in the method of Ramshaw et al., as modified by Morita et al., with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 See for example Shekhter et al. (Current Medicinal Chemistry, 2019:26:506-516).
2 See for example Peng et al. (Biomaterials, 2010;31(10):2755-2761).
3 See for example Chattopadhyay et a. (Biopolymers, 2014;101(8):821-833).
4 As evidenced by Millipore Sigma, PBS has a pH from 7-7.4.
Prosecution Insights