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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 10/27/2025 is acknowledged. The traversal is on the ground(s) that the applicant believes there to be no search burden on the examiner. This is not found persuasive because the applicant has not described why this would be the case and has merely claimed that there would be no burden. As previously explained the inventions are directed to creating compositions and to methods for treating pain and inflammation. Each invention would warrant separate fields for searching and examination and it cannot be predicted how the applicant will amend the claims which could drastically change the scope of each invention’s steps and the searching for the examiner.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/27/2025.
Claims 1-7 are being examined on the merits.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 are rejected under 35 U.S.C. 101 because the claimed composition is directed to a product of nature without significantly more. The first step of the eligibility analysis evaluates whether the claim falls within a statutory category (see MPEP 2106.03). Since the claim is directed to a composition comprising decellularized nucleus pulposus tissue, collagen, and genipin crosslinking agent or a lysyl oxidase and pepsin. the claim is a composition of matter. Step 2A prong one of the analyses evaluates whether the claim is a judicial exception (see MPEP 2106.04). Because the claim states the nature-based components which are decellularized nucleus pulposus tissue, collagen, and genipin crosslinking agent or a lysyl oxidase and pepsin, the markedly different characteristics is performed by comparing the nature-based product limitation to its natural counterpart.
The claims recite the naturally occurring components found within animals and plants. Animal and plant extracts are made by partitioning the starting material into separate compositions based upon some property such as solubility in a solvent, with the soluble compounds being in one composition and the insoluble being in another composition, which compositions are then generally separated into the solvent extract of that animal/plant versus the insoluble material composition that is generally discarded. Each composition has a different subset of the compounds originally present in the animal/plant material. Animal and plant extracts are purified by removing unwanted material from the remaining solvents. The closest naturally occurring counterparts of extracts are the same compounds found within the extract that are found in the animal/plant in an unseparated form, even when purified, which is chemically identical to the extracted compounds. All of these are naturally occurring in nature and are not markedly different from its naturally occurring counterpart in its natural state. The properties of the nature-based product as claimed are not markedly different than the properties of these naturally occurring counterparts found in nature as these activities would inherently be found within the plants they come from. The components which would give the activities claimed in the instant invention would inherently do the same in nature as there has been nothing done in the instant invention that would make them act in any different way.
Step 2A prong two evaluates whether the claim as a whole integrates the recited judicial exception into a practical application (see MPEP 2106.04(d)). This evaluation is performed by (a) identifying whether there are any additional recited elements in the claim beyond the judicial exception and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. This judicial exception is not integrated into a practical application because the applicant is only claiming the judicial exceptions together and in particular amounts. Although the applicant claims a hydrogel formulation, these formulations exist in nature because they are merely 3D water-retaining materials made from natural polymers like proteins and/or polysaccharides.
The claims do not integrate the judicial exceptions into a practical application because in this context, such integration for a claimed product would be a physical form of the specific practical application instead of a more general composition that is not so limited.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these components and their activity are already found naturally occurring in nature and the addition of an intended use does not impart any added benefit to the compounds or integrate the composition into a practical application.
Step 2 B evaluates whether the claim as a whole, amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP § 2106.05(b)).
Since the naturally-occurring components as-claimed are not found together in nature, admixing the ingredients into a single formulation is considered an ‘additional element’ which must be analyzed for eligibility. Admixing naturally-occurring plant extracts is well-understood, routine practice in the art and has been conducted for centuries. Admixing different components of plant and animal extracts together to form compositions for orthopedic issues is also well-understood, routine, ordinary practice in the field as evidenced by at least the following documents: US 20020072806 A1, US 20050084532 A1, US 20050119744 A1, US 20080095815 A1 and US 20130102690 A1.
Please also note, the mere modifying the concentration and proportions of the product/composition is not sufficient to remove the claimed composition from a judicial exception.
Therefore, admixing the claimed naturally-occurring ingredients at such a high degree of generality merely involves applying the natural principal and appears to be no more than a drafting effort to claim the judicial exception itself; a mixture of naturally-occurring components that is not markedly different from its’ closest-occurring natural counterpart and which does not offer significantly more than the judicial exception.
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.
Claims 1 and 6-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jefferey Moehlenbruck and Chandrashekhar Pathak (US20070003525A1).
Regarding claim 1, Moehlenbruck discloses a composition comprising nucleus pulposus tissue, at least a portion of which is decellularized, and at least a first cross-linkable viscosity control agent (see claim 67) and discloses “the soft, mucoid nucleus pulposus contains chondrocytes, which produce fibrils of collagen (primarily Type II collagen, but also Types IX, XI, and others) and large molecules of negatively charged, sulfated proteoglycans, as depicted in FIG. 1. These non-cellular components of the nucleus pulposus comprise a matrix that allows the cells to proliferate and is essential for a healthy intervertebral disc. Thus, the nucleus pulposus comprises a cellular component, a collagen component, and a proteoglycan component” (see 0007). Therefore it is understood that the composition has both collagen and dNP as claimed.
Claims 1 and 6-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nikunj Agrawal et. al. (From IDS, US20210046125A1).
Regarding claim 1, Agrawal discloses a decellularized tissue hydrogel comprising decellularized tissue, wherein the decellularized tissue contains native extracellular matrix proteins, wherein the decellularized tissue is cross-linked to form the hydrogel (see claim 1) and teaches wherein the decellularized tissue is nucleus pulposus (see figures 0047-0048 and 0108). As can be appreciated by those skilled in the art and the above rejection, native proteins would include collagen.
Regarding claim 6, Agrawal teaches wherein the decellularized hydrogel is performed by incubating the tissue with pepsin (see claims 7 and 13, 0012, 0020 etc.) and teaches that the pepsin is in concentrations of 1 to about 10 mg/mL (see 0127).
Regarding claim 7, Agrawal teaches after the decellularization process, the resulting decellularized tissue can undergo enzymatic processing and further processing to balance pH where necessary (see 0148) and teaches neutralizing the pH to 7.4 with 1 M sodium hydroxide (see 0159).
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 1-4 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Nikunj Agrawal et. al. (From IDS, US20210046125A1) and Athanasiou et. al. (WO2014065863A1).
Regarding claim 1, Agrawal discloses a decellularized tissue hydrogel comprising decellularized tissue, wherein the decellularized tissue contains native extracellular matrix proteins, wherein the decellularized tissue is cross-linked to form the hydrogel (see claim 1) and teaches wherein the decellularized tissue is nucleus pulposus (see figures 0047-0048 and 0108). As can be appreciated by those skilled in the art and the above rejection, native proteins would include collagen.
Regarding claim 6, Agrawal teaches wherein the decellularized hydrogel is performed by incubating the tissue with pepsin (see claims 7 and 13, 0012, 0020 etc.) and teaches that the pepsin is in concentrations of 1 to about 10 mg/mL (see 0127).
Regarding claims 4-5 and 7, Agrawal teaches after the decellularization process, the resulting decellularized tissue can undergo enzymatic processing and further processing to balance pH where necessary (see 0148) and teaches neutralizing the pH to 7.4 with 1 M sodium hydroxide (see 0159).
Agrawal does not specifically teach the composition to comprise of LOX.
Athanasiou teaches of compositions and methods for promoting collagen-crosslinking (see abstract).
Athanasiou teaches “a method of producing collagenous tissue possessing a high tensile strength, comprising: treating connective tissue cells under conditions effective for formation of enzyme-mediated collagen-crosslinks to produce collagenous tissue possessing a high tensile strength and wherein the conditions comprise culturing the connective tissue cells in the presence of 0.015 μg/ml to 1.5 mg/ml lysyl oxidase (LOX).
“The present disclosure generally relates to the field of tissue engineering. The collagenous tissue produced using methods of the present disclosure is extensively cross- linked and has high mechanical properties. Specifically, the present disclosure involves an enzyme-mediated collagen-crosslinking process to produce tissue such as cartilage, and to enhance its maturation and integration.[0010] In particular, the present disclosure provides methods of producing collagenous tissue possessing a high tensile strength, comprising: treating connective tissue cells under conditions effective for formation of enzyme-mediated collagen-crosslinks to produce collagenous tissue possessing a high tensile strength”.
Therefore it would have been obvious to persons having skill in the art before the effective filing date to use the LOX taught by Athanasiou in the invention of decellularized tissue which is cross-linked to form the hydrogel taught by Agrawal. Agrawal teaches wherein the decellularized tissue hydrogel would need to have a cross-linked component and so persons having ordinary skill in the art could look to Athanasiou as an option to incorporate LOX to cross-link collagen which is also discussed in Agrawal’s formulations. Optimizing the amount from 15 ng/ml down to 2ng/ml would have been an optimization well within the purview of any skilled artisan as these amounts are not far off from what is described by Athanasiou.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Nikunj Agrawal et. al. (From IDS, US20210046125A1) and Athanasiou et. al. (WO2014065863A1) as applied to claims 1-4 and 6-7a above and further in view of Ana K. Bedran-Russo (WO2007146841A2).
Agrawal does not specifically teach the composition to comprise of dNP and collagen however does not teach the composition to comprise of genipin.
Bedran-Russo teaches of collagen cross-linking agents. Bedran-Russo teaches “The invention relates to the development of compositions and methods for increasing the amount of collagen cross-linking in a mammalian tissue. A typical composition as described herein includes at least one cross-linking agent such as a bioflavonoid compound (e.g., proanthocyanidin), a grape seed extract, a Casein Phosphopeptide-amorphous Calcium Phosphate, or an iridoid compound (e.g., genipin) in an amount effective for increasing collagen cross-linking in the mammalian tissue in a pharmaceutically acceptable carrier.” (see abstract and claim 1).
Therefore it would have been obvious to persons having skill in the art before the effective filing date to use genipin in the invention of decellularized tissue which is cross-linked to form the hydrogel taught Agrawal, because this composition comprising of genipin can increase collagen cross-linking in mammalian tissues and are particularly useful for applying in compositions which require cross-linking collagen components as described in Agrawal’s invention. It would have been obvious to optimize the amount of genipin to that of the instant invention because this is well within the purview of any skilled artisan to determine optimal amounts of effective ranges especially given that the activities have been disclosed in the art.
Conclusion
Currently no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm.
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JACOB A BOECKELMAN Examiner, Art Unit 1655
/TERRY A MCKELVEY/ Supervisory Patent Examiner, Art Unit 1655