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 .
The preliminary amendment of 8/9/2024 has been received and entered. Claims 1-8, 11-19 and 21-23 are pending, all of which have been considered on the merits.
Priority
Acknowledgement is made of Applicants’ claim for benefit under 35 USC 120 as a continuation of prior-filed US Application 16/598597 (filed 10/10/2019; now abandoned), which claims benefit of prior-filed US Provisional applications 62/854647 (filed 5/30/2019) and 62/744204 (filed 10/11/2018).
Claim Interpretation
For clarity of record, the following comments are made regarding claim interpretation:
The specification defines “myofibers” as “the rod-like structures involved in muscle contraction and comprise proteins such as myosin, troponin, tropomyosin, and actinin. Long myofiber chains are found in and between the elongated muscle cells” (See spec ¶0030). This definition is in contrast to the teachings in the art, which uses the term “myofibers” to refer to the actual multi-nucleated muscle cell of skeletal muscle (See Cretiou et al, Pg. 25-26 “2.1.3 Skeletal Muscle Cells: General Characteristics and Morphological Aspects”). Muscle cells, per se, are not present ‘in and between the elongated muscle cells’. Furthermore, only skeletal muscle contains myofibers. The art uses the term “myofibrils” to refer to the rod-shaped organelle within (all) muscle cells responsible for contraction. Myofibrils comprise myofilaments, which are individual filamentous polymers of myosin, actin and associated proteins (See Cretiou et al Pg. 32, “2.1.4. Molecular Organization of Myofilaments in Striated Muscle Fibers”). The structure Applicants describe as “myofibers” appear to be “myofibrils”. However, applicants are permitted to be their own lexicographer, and thus the term “myofibers” will be interpreted as describing the actual myofibrils.
Claim 1 requires four active steps. For purposes of this office action, the steps will be identified/referenced with a lettering system (a)-(d):
(a) providing at least one muscle sample;
(b) contacting the at least one muscle sample with a solution containing trypsin at a concentration ranging from 10-8 % (w/v) to 10-4 % (w/v);
(c) decellularizing the at least one muscle sample to produce a decellularized muscle matrix;
(d) processing the decellularized muscle matrix to produce a collection of decellularized muscle matrix particles sized between about 3 µm and 5000 µm.
The claim further limits that steps (b) and (c) are controlled such that about 10-60% of the myosin normally found in the muscle sample (provided in (a)) is retained in the collection of decellularized muscle matrix particles.
The (c) decellularizing step must result in a decellularized muscle matrix. The specification defines “decellularized tissue” as “any tissue from which most or all of the cells that are normally found growing in the extracellular matrix of the tissue have been removed” (¶0032). The paragraph in the specification lists exemplary percentages of cells that must be removed, but these percentages are not part of the definition. The broadest reasonable interpretation, based on the definition, is a tissue from which greater than 50% of the cells that are normally found growing in the ECM of the tissue have been removed. In the claim, the phrase as measured with light microscopy does not require an actual step of measuring via light microscopy. The phrase is understood to mean that the percentage of cell removal can be measured/verified via light microscopy.
The (d) processing step results in production of a collection of decellularized muscle matrix particles that are (i) sized between about 3 µm and 5000 µm, (ii) are capable of supporting regeneration of muscle tissue, and (iii) retain about 10-60% of the myosin normally found in the muscle sample (provided in (a)). The specification does not definitely link any one or more specific physical property to ‘the ability to support muscle regeneration’. The specification identifies the full scope of decellularized muscle matrices described therein as capable of regenerating muscle tissue (See, e.g. ¶0008, 0074). Therefore, any particulate decellularized muscle matrix that meets the physical limitations of the instant claims (sized between about 3 µm and 5000 µm and retains about 10-60% of the myosin normally found in the muscle sample provided in (a)) will be considered to inherently be capable of supporting regeneration of muscle tissue.
The claim does not limit the form of the muscle implant. The collection of decellularized muscle matrix particles generated as a result of processing step (d) can read on the muscle implant. Or the collection of decellularized muscle matrix particles generated as a result of processing step (d) can be further modified to form an implant, such as compressing the particles into a sheet or construct, mixing the particles with a solution or gel, coating the particles onto another implant, etc.
Claim 16 and dependents are drawn to a muscle implant comprising a collection of muscle matrix particles, the particles being (i) sized between about 3 µm and 5000 µm, (ii) capable of supporting regeneration of muscle tissue, (iii) decellularized, and (iv) trypsin treated so as to retain about 10-60% of the myosin normally found in an unprocessed muscle sample. The implant must be in a form suitable for implantation. Any tissue meeting these physical requirements is considered inherently capable of supporting muscle tissue regeneration. Claim 13 further recites product-by-process limitations regarding the concentration of trypsin used to generate the trypsin-treated particulate decellularized muscle matrix. The product-by-process limitations are considered only in so far as the process of production affects the structure of the final product. See MPEP 2113. In this case, the effect of the trypsin treatment is that the muscle matrix particles must retain about 10-50% myosin content. The effect of trypsin is dependent on concentration, enzyme activity and duration of contact.
Claim 22 and dependents are drawn to methods of treatment. The claim does not limit the patient population being treated. The method comprises a single step: injecting to the patient a muscle implant comprising particulate decellularized muscle matrix comprising at least some of the myofibers normally found in an unprocessed muscle sample. The muscle implant may comprise elements in addition to the particulate decellularized muscle matrix.
Claim Objection
Claim 13 is objected to for a minor informality:
In line two, “processed” is mis-spelled [sic: unprecessed]. Correction is required.
Claim Rejections - 35 USC § 102
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 22 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al (US 2015/0282925).
Xu et al teach muscle implants that retain at least some of the myofibers found in muscle tissue prior to processing, methods of making the muscle implants and methods of using the muscle implants (See abstract).
Initially it is noted that Xu et al define “myofibers” as rod-like structures involved in muscle contraction and comprise proteins such as myosin, troponin, and actinin (See ¶0022). This is different than the art accepted definition of “myofibers” which is the actual multi-nucleated muscle cells of skeletal muscle. The definition provided by Xu et al corresponds to the art accepted definition of “myofibrils”. However, as Xu et al set forth an explicit definition, the definition of Xu et al controls for the publication. The “myofibers” of Xu et al are the same as the “myofibers” of the instant application.
Regarding claim 22: In Example 3 Xu et al teach creating an excision wound, and then group 3 received filling of the wound with a paste-like mixture of hyaluronic acid solution and a decellularized porcine muscle powder that retained some myofibers (200 mg/mL).
The applied paste reads on a muscle implant. The decellularized porcine muscle powder reads on particulate decellularized muscle matrix. Xu et al state the powder retains “some” myofibers, which satisfies the limitation containing at least some of the myofibers normally found in an unprocessed muscle sample. The filling of the wound reads on treatment, and is considered injecting.
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.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Xu et al (US 2015/0282925).
The teachings of Xu et al are set forth above.
Regarding claim 23: Xu et al does not specifically comment on the % of myosin retained in the muscle implant utilized in Example 3, group 3.
However, per the definition of Xu et al, ‘myofibers’ are the rod-like structures involved in muscle contraction and comprise the myosin present in muscle tissue. Myosin is only present in the rod-like structures involved in muscle contraction (in the ‘myofibers’ as defined by Xu et al). Therefore, it is reasonable to conclude that the proportion of myofibers retained is at least roughly equivalent to the proportion of myosin retained. Xu et al teach that roughly 20-80% of myofibers are to be retained (including specific values of about 20% and about 30% (See ¶0035); thus about 20-80%, and specifically 20% and/or 30% of myosin will also necessarily be retained in the decellularized particulate muscle matrix of Xu et al. This conclusion is based on inherency. As the examiner has established a reasonable basis for concluding the myosin content of the muscle implant is the same as the % of myofibers retained, the burden is shifted to Applicants to show otherwise. See MPEP 2112.01.
It would therefore have been prima facie obvious to have made the particulate decellularized muscle matrix used in group 3 of Example 3 with muscle matrix treated to be decellularized and to retain 20% or 30% of myofibers, thus resulting in retention of 20% or 30% of myosin. This conclusion of obviousness is based on preferred teachings in the reference.
This retained proportion of myosin meets the limitation of claim 23.
Allowable Subject Matter
Claims 1-8, 11-12, 14-19 and 21 are allowed.
Claim 13 would be allowable if amended to correct the spelling error.
The following is a statement of reasons for the indication of allowable subject matter: Claim 1 is directed to a method of preparing a specific muscle implant, and claim 16 is directed to the specific muscle implant thereby produced, broadest reasonable interpretation set forth above. The closest prior art is the inventors’ previous work Xu et al (US PGPub 2015/0282925). Xu et al teaches a similar method for producing decellularized muscle matrix, including contacting muscle matrix with trypsin and decellularizing the trypsin-treated muscle matrix. Though the specification of Xu et al discloses the decellularized trypsin-treated muscle matrix can be further particulated, and though Xu et al teach that the decellularized muscle matrix material of their disclosure are capable of supporting regeneration of muscle tissue, the experimental evidence in Xu et al shows that powdered decellularized muscle matrix was incapable of supporting regeneration of muscle tissue. Xu et al can only be relied upon to show that powdered decellularized muscle matrix (of unknown size) did not support muscle regeneration, and a piece of decellularized muscle matrix of 1 cm x 1 cm did support muscle regeneration. There is insufficient evidence in Xu et al, or the prior art, to base a conclusion that decellularized muscle tissue produced via the method of Xu et al with particle sizes of about 3 microns to 5000 microns would have been successful in regenerating muscle tissue. Therefore no rejection is made, the claims are allowed over the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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