DETAILED ACTION
Formal Matters
Claims 1-17 are pending and under examination.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a continuation of PCT/CN2022/091946 filed on 5/10/2022, which claims priority from CN202210495091.5 filed on 5/7/2022.
Information Disclosure Statements
The information disclosure statement (IDS) filed on 10/28/2024 has been considered by the examiner.
Claim Objections
Claims 9 and 10 are objected to for the abbreviated form of PBS without first writing it out as phosphate-buffered saline in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 7, 8, 9, 11, 12 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CN109568653A (published 4-5-2019, with English translation).
Note that claim 1 is to a hydrogel and claim 7 is a production method, and thus, “for heart failure treatment” is toward the intended use. If the composition and methods of the prior art teaches similar components and steps, then it will teach the claims.
As the claims provide recombinant collagen as an active agent, if the prior art teaches recombinant collagens it will read on this limitation.
CN ‘653 teaches a human collagen protein gel dressing with recombinant collagen, sodium alginate and calcium chloride to mix and form the gel (claims 1-3 of CN ‘653). CN ‘653 teaches a buffer salt with sodium chloride, potassium chloride, and phosphate salts that allows the pH of the hydrogel to be from 7.3-7.5 (claims 4 and 5 of CN ‘653), which is the formulation of PBS (phosphate buffered saline). Embodiment 1 teaches collagen type III in the formulation. Embodiment 1 teaches “regenerative agent includes: recombined human collagen type by weight: 5-30 parts；CaCl2: 1-10 parts, with H2O:65-95 parts” and “the crosslinking agent includes: recombined human collagen type by weight: 5-30 parts；Sodium alginate: 0.5-5 Part and H2O:65-95 parts”. Embodiment 1 teaches mixing the regenerative agent and the crosslinking agent. Embodiment 5 provides for synchronizing to spray on a wound surface using a syringe. CN ‘653 provides for compositions that are hydrogels in a from that can be injectable (via teach of using syringe to deliver) where it contains such amounts of sodium alginate, calcium chloride and recombinant collagen (an active agent) as well as making them by making one composition with the calcium chloride and another with the sodium alginate then mixing. These compositions are loaded with the collagen as it will be contained in the hydrogels made.
Claim(s) 1, 3, 7, 8, 11, 14 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CN111888524A (published 11-6-2020, with English translation).
CN ‘524 teaches “a tissue filling material, a preparation method thereof, a tissue engineering scaffold and application thereof, wherein the tissue filling material comprises the following raw materials: alginate, metal cation cross-linking agent and water-soluble biodegradable pore-forming filling material, wherein the content of the raw materials in the tissue filling material is 0.1-20 wt%, and the balance is water for injection” (abstract). CN ‘524 teaches “a component A, a component B and injection water, wherein the component A contains alginate, the component B contains a metal cation crosslinking agent, the component A and/or the component B also contains a water-soluble biodegradable pore-forming filling material, the component A and the component B are fully stirred to form an ionic crosslinking type hydrogel structure, and the pore-forming filling material is uniformly distributed in the ionic crosslinking type hydrogel structure; the content of the alginate in the tissue filling material is 0.1-20 wt%, the content of the metal cation cross-linking agent in the tissue filling material is 0.1-20 wt%, and the content of the pore-forming filling material in the tissue filling material is 0.1-20 wt%.” (claim 1 of ‘524). CN ‘524 teaches the pore-forming material will have a biological activity to promote the growth of tissue cells and regulate cell adhesion, proliferation and differentiation and provides for materials like transforming growth factor, platelet-derived growth factor and fibroblast growth factor (claims 2-5 of ‘524). CN ‘524 provides for protein material including collagen (claim 4 of ‘524). Example 7 provides for alginate and collagen material that is injectable, provides for treatment of heart failure diseases and provides a method that involves a solution of calcium alginate mixing with sodium alginate 2% and making a material with a modulus of 7330 Pa (examples 7 and paragraphs 4-5, also claim 14 of ‘524). Example 7 provides for gelation time where the items are in water, thus, making a hydrogel. Example 10 teaches a material with calcium alginate, sodium alginate and laminin that can be in a syringe and a modulus of 6kPa (6000 Pa). Example 36 teaches calcium alginate, hyaluronic acid (used for the heart) and sodium alginate in a hydrogel that provides for treating heart failure by providing the hydrogel with the tissue filler by in vivo injection. Examples 7 and 36 provide for mixing the premix with calcium alginate and collagen or hyaluronic acid with the premix having the sodium alginate. Example 21 provides for using calcium chloride instead of calcium alginate.
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 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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 pre-AIA 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 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 pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 3 and 4 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over CN109568653A (published 4-5-2019) and Duan et al (MRS Advances, 2017, volume 2, pages 1309-1314).
CN ‘653 teaches the claims as discussed above.
Although CN ‘653 provides for a hydrogel with similar ingredients and amounts, it does not discuss storage modulus.
Duan provides that hydrogels are useful for many applications in tissue engineering and drug delivery (abstract). Duan teaches that alginate gels have properties making them suitable as carriers for cells and drug delivery (abstract). Duan teaches that addition of collagen and fibrin would reinforce the mechanical properties of alginate to make it a strong scaffold material (abstract). Experimental details note that CaCl2 is used for gelation (page 1310). Duan teaches that 0.5% alginate gels have storage moduli G’ of 600-1000 Pa while the graphs in figure 1a show 0.5% alginate gels with just above 1000 Pa and those with RGD alginate under 10000 Pa. Also figure 3a provides for values between 100 and 5000 Pa for alginate gels having collagen/alginate/fibrin at different concentrations. Thus, Duan sees storage modulus as an adjustable value based on amounts of collagen and alginate used in the hydrogels.
One of ordinary skill in the art before the time of filing would have adjusted the ingredient amounts and ingredients in teachings of CN ‘653 by teachings of Duan to achieve hydrogels with storage moduli in its teachings which are seen as optimal for uses in tissue engineering and drug delivery. Therefore, there was a reasonable expectations of modifying amounts of the alginate and collagen in CN ‘653 with teachings of Duan to achieve storage modulus values of applicant’s claims, which are seen as beneficial for drug delivery/tissue engineering materials.
Claims 5 and 12 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over CN111888524A (published 11-6-2020, with English translation).
CN ‘524 teaches the claims as discussed above.
CN ‘524 does not provide the mesh aperture range and only provides an overlapping range of metal cation cross-linking agent in the tissue filling material is 0.1-20 wt%.
CN’524 teaches the tissue filling material has simple preparation process, can be prepared by mixing, and can adjust the aperture size and porosity of the hydrogel by changing the dosage of the pore-forming filler (example 36). CN ‘524 teaches porous rectangular structure and three dimensional porous structure (English translation, also figure 3-5). CN ‘524 teaches calcium chloride as an alternative crosslinking agent (English translation and example 21). CN ‘524 teaches “due to the three-dimensional porous structure, the material can initially support the cardiac tissue in vivo, initially adhere cardiac muscle cells and enable the cardiac muscle cells to enter the material for growth, and can adapt to the growth of cells, the delivery of nutrient flow and the discharge of metabolites.” Such a porous structure with apertures would represent a mesh structure.
One of ordinary skill in the art before the time of filing would have used calcium alginate or calcium chloride as crosslinking agents within the overlapping range of CN ‘524 to provide for making hydrogels of applicant’s claims while also making adjustment to the hydrogel to control aperture size and porosity of the hydrogels for optimization. Therefore, there was a reasonable expectation of success in utilizing the teachings of CN ‘524 to provide for the concentrations of calcium crosslinking agent and the ability to adjust aperture sizes as desired for the entry of cells into the porous hydrogel.
Claims 9-10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over CN111888524A (published 11-6-2020, with English translation) and Gemeinhart US 20090291115.
CN ‘524 teaches the claims as discussed above.
CN ‘524 does not teach the use of PBS in making the solutions.
Gemeinhart teaches making superporous hydrogels for cells (abstract). Gemeinhart teaches DPBS (Dulbecco's Phosphate-Buffered Saline) as a material for the hydrogels (paragraph 31). Gemeinhart teaches using the DPBS to make the hydrogels (paragraphs 34 and 40). Gemeinhart also teaches materials such as sodium alginate (claim 8 of Gemeinhart). Gemeinhart teaches the hydrogel for implantation to a subject (paragraph 8).
One of ordinary skill in the art before the time of filing would have used a PBS like DPBS to make a suitable hydrogel that is suitable for use in the body by the combined teachings of the prior art since DPBS is seen as an acceptable ingredient to combine the elements to make the hydrogel. In regards to adjusting the volume ratio of adding one solution to the other, although CN ‘524 teaches a 1:1 ratio in examples, one of ordinary skill in the art would have adjusted the volume ratio depending on concentrations of the agents in each solution. Therefore, there was a reasonable expectation of success in combining the teachings of the references to produce production methods where PBS is used in making the hydrogel composition.
Claims 2, 4, 6, 13, 15, and 16 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over CN111888524A (published 11-6-2020, with English translation) and Pupkaite et al (ACS Biomaterials Science and Engineering, 2020, volume 6, pages 4256-4265).
CN ‘524 teaches the claims as discussed above.
CN ‘524 teaches collagen as an active material, but does not teach recombinant humanized collagen type III.
Pupkaite teaches injectable human recombinant collagen III hydrogel for treating myocardial infarction with an amount of 1% being used (abstract). Pupkaite teaches early intramyocardial delivery of rHCIII hydrogel can improve cardiac function in an infarcted heart (conclusion). Pupkaite teaches an increase in the concentration can be detrimental to the heart due to inflammation (Conclusion).
One of ordinary skill in the art before the time of filing would have used recombinant human type III collagen as the collagen in teachings of CN ‘524 as it is seen to help improve heart function when delivered by injectable hydrogel to the infarcted, failing heart. In regards to the amount of the collagen used, CN ‘524 provides that increasing the amount was detrimental which would prompt one of ordinary skill in the art to use amounts of the rHCIII lower than 1% instead for its therapeutic benefit while reducing the chances of inflammation in the heart. In regards to mixing solutions in ratios, CN ‘524 teaches mixing of the calcium alginate/active (collagen) solution and the sodium alginate solution in making the hydrogels and one of ordinary skill in the art would adjust the solution combination ratio based on concentrations of ingredients found in each mixture to provide a properly formed hydrogel. Therefore, there was a reasonable expectation of success in combining the teachings of CN ‘524 and Pupkaite and obtaining hydrogels and preparation methods for said hydrogels of applicant’s claims as recombinant human collagen type III is a beneficial collagen for treating a heart failure condition.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached on M-F 9:00 am to 6:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached on (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARK V STEVENS/
Examiner, Art Unit 1613
Prosecution Insights