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 .
Detailed Action
This action is in response to the papers filed July 9, 2026.
Amendments
Applicant's response and amendments, filed July 9, 2026, to the prior Office Action is acknowledged. Applicant has cancelled Claims 2, 4-6, 9, 11-13, 16, 19-20, 24, 26, 29, 31-33, 36, and 40, amended Claims 1, 7-8, 15, and 28, and withdrawn Claims 34-35, 37-39 and 41-42.
Claims 1, 3, 7-8, 10, 14-15, 17-18, 21-23, 25, 27-28, 30, 34-35, 37-39, and 41-42 are pending.
The amendment to the claims filed on July 9, 2026 does not comply with the requirements of 37 CFR 1.121(c). Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
The correct status of Claims 10, 14, 18, 21-22, and 30 is (Withdrawn).
Election/Restrictions
Applicant has elected with traverse the invention of Group III, claim(s) 1, 3-4, 7-8, 10, 14-15, 17-18, 21-23, 25, 27-28, and 30, drawn to a method of producing an enriched tissue extract.
Because applicant did not distinctly and specifically point out the supposed errors in the Group or species restriction requirement, the election has been treated as an election without traverse and the restriction and election requirement is deemed proper and therefore made final (MPEP §818).
Within Group III, Applicant has elected without traverse the following species, wherein:
i) the alternative biological sample is muscle tissue, as recited in Claim 7;
ii) the alternative tissue extract is exosomes, as recited in Claim 28;
iii) the alternative incubating step is Claim 25, step (ii);
iv) the alternative additional method step is physical stress via mechanical stress, as recited in Claim 3; and
vi) the alternative additional method step induces a stress response in the live cells, as recited in Claim 4(i).
Claims 1, 3, 7-8, 10, 14-15, 17-18, 21-23, 25, 27-28, 30, 34-35, 37-39, and 41-42 are pending.
Claims 10, 14, 18, 21-22, 30, 34-35, 37-39, and 41-42 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1, 3, 7-8, 15, 17, 23, 25, and 27-28 are under consideration.
Priority
This application is a 371 of PCT/US2020/072805 filed on June 8, 2022. Applicant’s claim for the benefit of a prior-filed application provisional application 63/208,766 filed on June 9, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on July 9, 2026 that has been considered.
The signed and initialed PTO Forms 1449 are mailed with this action.
Claim Objections
1. Claim 28 stands objected to because of the following informalities:
Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). See MPEP §608.01(m).
The multiple ‘wherein’ clauses should be separated by line indentation.
Appropriate correction is required.
The Examiner suggests the following format:
“claim 1, wherein the enriched…; and
wherein the signaling molecules…”, for example.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
2. The prior rejections of Claim 4 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, and under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in light of Applicant’s cancellation of the claim.
3. The prior rejection of Claim 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of Applicant’s cancellation of “substantially”.
4. The prior rejection of Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn in light of Applicant’s amendment to the claim limiting to a deceased donor.
5. Claim 8 stands rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 recites the step of providing a biological sample comprising live cells.
Claim 7 recites wherein the biological sample comprises tissue or isolated cells from muscle.
Claim 8 recites wherein the tissue a single type of tissue and comprises a portion of tissue or a plurality of tissue pieces.
Claim 8 is considered to not further limit Claim 7 because it is natural law of anatomy and cell biology that the step providing a biological sample comprising live cells, including muscle tissue or isolated muscle cells will necessarily yield:
i) a single type of tissue and is substantially free of other types of tissue; or
ii) a portion of tissue or a plurality of tissue pieces.
To put it another way, mere recitation of each isolated cell/tissue composition possibilities (Claim 8) that are naturally achieved per Claims 1 and 7 fails to further limit Claims 1 and 7.
Mere recitation of both states of reality (portion or plurality) fails to further limit the independent claim and/or Claim 7.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
6. The prior rejection of Claim(s) 1, 3-4, 7-8, 15, 17, 23, and 28 under 35 U.S.C. 102(a)(1) as being anticipated by Zanotti et al (Exosomes and exosomal miRNAs from muscle-derived fibroblasts promote skeletal muscle fibrosis, Matrix Biology 74: 77-100, 2018) is withdrawn in light of Applicant’s amendment to independent Claim 1 to recite the biological sample is a tissue and the step of incubating the tissue is performed within 72 hours of obtaining the biological sample from the donor, a limitation Zanotti et al do not teach.
7. The prior rejection of Claim(s) 1, 3-4, 7-8, 15, 17, 23, 25, and 28 under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al (Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1beta Production Through the Inhibition of the NF-kB Signaling Pathway in Macrophages, Frontiers in Immunology 10: e1310, 17 pages, doi.10.3389/fimmu.2019.01310; available online June 20, 2019) is withdrawn in light of Applicant’s amendment to independent Claim 1 to recite the biological sample is a tissue and the step of incubating the tissue is performed within 72 hours of obtaining the biological sample from the donor, a limitation Wang et al do not teach.
8. The prior rejection of Claim(s) 1, 3-4, 7-8, 15, 17, 23, 25, and 28 under 35 U.S.C. 102(a)(1) as being anticipated by Guo et al (Stimulating Extracellular Vesicles Production from Engineered Tissues by Mechanical Forces, Nano Letters 21: 2497-2504, available online March 12, 2021) is withdrawn in light of Applicant’s amendment to independent Claim 1 to recite the biological sample is a tissue and the step of incubating the tissue is performed within 72 hours of obtaining the biological sample from the donor, a limitation Wang et al do not teach.
9. Claim(s) 1, 3, 17, 23, 25, and 27-28 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Loppnow et al (Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6, J. Clin. Invest. 85(3): 731-738, 1990).
With respect to Claim 1, Loppnow et al is considered relevant prior art for having taught a method of producing an enriched tissue extract, the method comprising the step(s) of:
(a) providing a biological sample obtained from a donor and comprising live cells (e.g. pg 732, col. 1, Methods, human saphenous veins);
(b) incubating the biological sample in an extraction solution for a period of time sufficient for biologically active components to be extracted from the biological sample thereby forming an enriched tissue extract (e.g. pg 732, col. 1, Methods, human saphenous veins); and
(c) separating the enriched tissue extract from the processed biological sample (e.g. pg 732, col. 1, Methods, “supernatants were harvested”; pg 734, col. 2, “Saphenous vein segments produce IL6 during short-term culture”).
Loppnow et al taught wherein the human saphenous veins were “processed immediately” (e.g. pg 732, col. 1, Methods), and thus is considered to reasonably fulfill “wherein the incubating is performed within 72 hours of obtaining the biological sample from the donor”.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
Instant specification fails to disclose an element of criticality for the limitation “wherein the incubating is performed within 72 hours of obtaining the biological sample from the donor” as it pertains to a method of producing an enriched tissue extract from a primary biological sample obtained from a donor. Rather, the substantive issue is the step of culturing a primary biological sample obtained from a donor, and separating the culture medium or other tissue extract from the thus-cultured primary biological sample.
With respect to Claim 3, Loppnow et al taught wherein the method comprises administering a physical stress, more specifically a mechanical stress, to the biological sample prior to the incubating step (e.g. pg 732, col. 1, Preparation of….human saphenous veins, “cut into portions”, “stripped”, “washed and cut into 2x2 mm portions”, placement into tissue culture) which is/are considered to reasonably fulfill administering a physical stress, more specifically a mechanical stress, recited at a high level of generality.
With respect to Claim 17, Loppnow et al taught wherein the biological sample is from a human donor subject (e.g. pg 732, col. 1, Methods, human saphenous veins).
With respect to Claim 23, Loppnow et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pg 732, col. 1, Methods, human saphenous veins).
With respect to Claim 25, Loppnow et al taught wherein the incubating step comprises soaking the biological sample in an extraction solution for a period of 24 hours (e.g. pg 732, col. 1, Methods, human saphenous veins, “was added for 24h”). Those of ordinary skill in the art would have reasonably understood that the culture conditions are performed at least at room temperature (syn. 25C), as such is routine practice in the art.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
Instant specification fails to disclose an element of criticality for the temperature limitation “2C to 42C”, as it pertains to a method of producing an enriched tissue extract from a primary biological sample obtained from a donor. Loppnow et al do not teach culturing the tissue sample at a temperature below 2C, nor above 42C. Those of ordinary skill in the art would have reasonably understood that the culture conditions are performed at least at room temperature (syn. 25C) or 37C, as such is routine practice in the art.
With respect to Claim 27, Loppnow et al taught wherein the separating step comprises separating the enriched tissue extract from the biological sample using at least centrifugation (e.g. pg 732, col. 1, Methods, “supernatants were harvested and centrifuged”).
With respect to Claim 28, the term "comprising", per “the tissue extract comprises…”, is open-ended and allows for additional, unrecited elements in the claimed tissue extract. MPEP 2111.03 specifically sets forth that the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Loppnow et al taught wherein enriched tissue extract comprises signaling molecules such as IL-6, amino acids, and growth factor proteins (e.g. Figure 4), as there is no objective evidence of record that the step of centrifuging the culture supernatant at 1,500g (pg 732, col. 1, Methods, “supernatants were harvested and centrifuged”) physically removes and separates IL-6 from other extract components such as growth factor proteins and/or other signaling molecules, per natural law(s) of biology, chemistry and physics, and per the logic of the claimed limitations recited at a high level of generality.
Since the Patent Office does not have the laboratory facilities for examining and comparing Applicants' tissue extract recited at a high level of generality with the tissue extract(s) of the prior art reference(s), the burden is upon Applicants to show a distinction between the material structural and functional characteristics of the claimed tissue extract and the tissue extract(s) of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Thus, Loppnow et al anticipate the claims and/or render the claims prima facie obvious.
10. Claim(s) 1, 3, 7-8, 23, 25, and 27-28 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Roco-Rivada et al (Muscle tissue as an endocrine organ: Comparative secretome profiling of slow-oxidative and fast-glycolytic rat muscle explants and its variation with exercise, J. Proteomics 75: 5414-5425, 2012).
With respect to Claim 1, Roco-Rivada et al is considered relevant prior art for having taught a method of producing an enriched tissue extract, the method comprising the step(s) of:
(a) providing a biological sample obtained from a donor and comprising live cells (e.g. pg 5415, col. 2, Methods, 2.2 Muscle tissue secretome collection and processing);
(b) incubating the biological sample in an extraction solution for a period of time sufficient for biologically active components to be extracted from the biological sample thereby forming an enriched tissue extract; and
(c) separating the enriched tissue extract from the processed biological sample (e.g. pg 5416, col. 1, Methods, 2.2 Muscle tissue secretome collection and processing, “secretomes were immediately processed…”).
Roco-Rivada et al taught wherein the muscle pieces were “processed for secretome collection based on an optimized in-house protocol in order to attenuate tissue damage” (e.g. pg 5416, col. 1, Methods, 2.2 Muscle tissue secretome collection and processing), and thus is considered to reasonably fulfill “wherein the incubating is performed within 72 hours of obtaining the biological sample from the donor”.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
Instant specification fails to disclose an element of criticality for the limitation “wherein the incubating is performed within 72 hours of obtaining the biological sample from the donor” as it pertains to a method of producing an enriched tissue extract from a primary biological sample obtained from a donor. Rather, the substantive issue is the step of culturing a primary biological sample obtained from a donor, and separating the culture medium or other tissue extract from the thus-cultured primary biological sample.
With respect to Claim 3, Roco-Rivada et al taught wherein the method comprises administering a physical stress, more specifically a mechanical stress, to the biological sample prior to the incubating step (e.g. pg 5416, col. 2, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle tissues….removed”, “tissues were processed”, “muscle pieces were incubated…”, placement into tissue culture), which is/are considered to reasonably fulfill administering a physical stress, more specifically a mechanical stress, recited at a high level of generality.
With respect to Claims 7-8, Roco-Rivada et al taught wherein the biological sample tissue comprises muscle (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle pieces were incubated…”).
With respect to Claim 23, Roco-Rivada et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing).
With respect to Claim 25, Roco-Rivada et al taught wherein the incubating step comprises soaking the biological sample in an extraction solution for a period of 12 hours (e.g. pg 5417, col. 1, Methods, 2.2 Muscle tissue secretome collection and processing, “incubated for 12h”). Those of ordinary skill in the art would have reasonably understood that the culture conditions are performed at least at room temperature (syn. 25C), as such is routine practice in the art.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
Instant specification fails to disclose an element of criticality for the temperature limitation “2C to 42C”, as it pertains to a method of producing an enriched tissue extract from a primary biological sample obtained from a donor. Roco-Rivada et al do not teach culturing the tissue sample at a temperature below 2C, nor above 42C. Those of ordinary skill in the art would have reasonably understood that the culture conditions are performed at least at room temperature (syn. 25C) or 37C, as such is routine practice in the art.
With respect to Claim 27, Roco-Rivada et al taught wherein the separating step comprises separating the enriched tissue extract from the biological sample using at least centrifugation (e.g. pg 5417, col. 1, Methods, 2.2 Muscle tissue secretome collection and processing, “Secretomes were immediately processed….by ultracentrifugation”).
With respect to Claim 28, the term "comprising", per “the tissue extract comprises…”, is open-ended and allows for additional, unrecited elements in the claimed tissue extract. MPEP 2111.03 specifically sets forth that the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Roco-Rivada et al taught wherein enriched tissue extract comprises signaling molecules such as IL-6, amino acids, and growth factor proteins (e.g. pg 5417, col. 2, “myokine (IL-6)”; “161 proteins”; Figure 2; Tables 1-3), as there is no objective evidence of record that the step of centrifuging the culture supernatant physically removes and separates IL-6 from other extract components such as growth factor proteins and/or other signaling molecules, per natural law(s) of biology, chemistry and physics, and per the logic of the claimed limitations recited at a high level of generality.
Since the Patent Office does not have the laboratory facilities for examining and comparing Applicants' tissue extract recited at a high level of generality with the tissue extract(s) of the prior art reference(s), the burden is upon Applicants to show a distinction between the material structural and functional characteristics of the claimed tissue extract and the tissue extract(s) of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Thus, Roco-Rivada et al anticipate the claims and/or render the claims prima facie obvious.
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 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 of this title, 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(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 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.
11. The prior rejection of Claim(s) 1, 3-4, 7-8, 15, 17, 23, 25, and 28 under AIA 35 U.S.C. 103 as being unpatentable over Zanotti et al (2018; of record), as applied to Claims 1, 3-4, 7-8, 15, 17, 23, and 28 above, and in further view of Wang et al (available online June 20, 2019; of record) and Guo et al (available online March 12, 2021; of record) is withdrawn in light of Applicant’s amendments to the claims discussed above necessitating new grounds of rejection.
12. Claim(s) 7-8, 15, 17, 23, and 25 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Loppnow et al (1990; of record) and Roco-Rivada et al (2012; of record), and further in view of Popescu et al (Identification of telocytes in skeletal muscle interstitium: implication for muscle regeneration, J. Cell. Mol. Med. 15(6): 1379-1392, 2011).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
The teachings of Loppnow et al and Roco-Rivada et al are discussed above, and incorporated herein.
Neither Loppnow et al nor Roco-Rivada et al teach wherein the tissue sample is obtained from a deceased donor subject.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 15, Popescu et al is considered relevant prior art for having taught a method of obtaining a biological tissue sample from a subject, e.g. mouse skeletal muscle tissue explants, wherein the subject is a deceased donor (e.g. pg 1380, col. 2, Methods, “sacrificed by cervical dislocation”).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in cell biology and cell culture methods. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to try obtaining a biological tissue sample from a deceased donor subject with a reasonable expectation of success because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.” One of ordinary skill in the art would have understood that there are only two states of reality from which to obtain the donor biological tissue sample from a donor subject: dead or alive. The number of possible states of being, living or dead, from which to choose is neither astronomical nor insurmountable, and as taught by Popescu et al, it is routine practice in the art to sacrifice (syn. render deceased) an animal subject prior to obtaining a biological tissue sample from said [deceased] donor subject.
Prior to the effective filing date of the instantly claimed invention, it also would have been obvious to one of ordinary skill in the art to substitute a living donor, as taught by Loppnow et al and/or Roco-Rivada et al, with a deceased donor, as taught by Popescu et al, from which to obtain a biological tissue sample with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would have been motivated to substitute a living donor with a deceased donor from which to obtain a biological tissue sample because Popescu et al successfully demonstrated both options, muscle tissue explants from a deceased mouse subject, and muscle tissue explants from living human subjects (e.g. pg 1380, Methods). One of ordinary skill in the art would have understood that there are only two states of reality from which to obtain the donor biological tissue sample from a donor subject: dead or alive.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claims 7-8, Roco-Rivada et al taught wherein the biological sample tissue comprises muscle (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle pieces were incubated…”).
Popescu et al taught wherein the biological sample tissue comprises muscle (e.g. e.g. pg 1380, col. 1, Methods, Tissue samples, “human skeletal muscle samples”).
With respect to Claim 23, Roco-Rivada et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing).
Popescu et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pg 1380, col. 2, Methods, “explants were covered with…culture medium…”).
With respect to Claim 17, Loppnow et al taught wherein the biological sample is from a human donor subject (e.g. pg 732, col. 1, Methods, human saphenous veins).
Popescu et al taught wherein the biological sample is from a human donor subject (e.g. pg 1380, col. 1, Methods, Tissue samples, “human skeletal muscle samples”).
With respect to Claim 25, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
Instant specification fails to disclose an element of criticality for the temperature limitation “2C to 42C”, as it pertains to a method of producing an enriched tissue extract from a primary biological sample obtained from a donor. Loppnow et al and Roco-Rivada et al do not teach culturing the tissue sample at a temperature below 2C, nor above 42C. Those of ordinary skill in the art would have reasonably understood that the culture conditions are performed at least at room temperature (syn. 25C) or 37C, as such is routine practice in the art.
Popescu et al taught the explants were cultured at 37C (e.g. pg 1380, col. 2, Cell Culture).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
13. Claim(s) 3, 7-7, 17, 23, 25, and 27-28 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Loppnow et al (1990; of record) and Roco-Rivada et al (2012; of record), and further in view of Wang et al (available online June 20, 2019; of record) and Guo et al (available online March 12, 2021; of record).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
The teachings of Loppnow et al and Roco-Rivada et al are discussed above, and incorporated herein.
Neither Loppnow et al nor Roco-Rivada et al teach wherein the incubating step comprises: (ii) agitating the sample in an extraction solution.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 25(ii), Wang et al is considered relevant prior art for having taught a method of producing exosomes from ligament cells, the method comprising the step of incubating the cells in an extraction solution, e.g. culture medium, wherein the incubating step further comprises agitating the cells (e.g. Abstract, “We examined the secretion of exosomes from… cells stimulated with cyclic stretch (syn. agitation)”).
Similarly, Guo et al is considered relevant prior art for having taught a method of producing exosomes from muscle cells, the method comprising the step of incubating the cells in an extraction solution, e.g. culture medium, wherein the incubating step further comprises agitating the cells (e.g. Abstract, “applying mechanical stimuli, including flow and stretching (syn. agitation)”).
Guo et al taught that current extracellular vesicle production from cells relies heavily on 2D cell culture, which is not only less physiologically relevant to cells, but also requires substantial culture medium and space. However, by applying mechanical forces, including agitation, extracellular vesicle production is significantly enhanced (e.g. Abstract).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to modify the in vitro method of producing an enriched tissue extract from a biological tissue sample, said tissue extract comprising secreted molecules including exosomes from a biological sample of cells, e.g. muscle cells, to comprise the step of agitating the tissue cells during the incubation step with motivation and a reasonable expectation of success because those of ordinary skill in the art previously recognized and successfully reduced to practice:
i) culturing the artisan’s cell type of interest, including reconstructed tissues comprising muscle cells, in a culture medium under conditions of agitation, e.g. cyclic stretch and/or mechanical stimulation, to produce extracellular vesicles, including exosomes (Wang et al, Guo et al); and
ii) current extracellular vesicle production from cells relies heavily on 2D cell culture, which is not only less physiologically relevant to cells, but also requires substantial culture medium and space; however, by applying mechanical forces, including agitation, extracellular vesicle production is significantly enhanced (Guo et al).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 3, Loppnow et al taught wherein the method comprises administering a physical stress, more specifically a mechanical stress, to the biological sample prior to the incubating step (e.g. pg 732, col. 1, Preparation of….human saphenous veins, “cut into portions”, “stripped”, “washed and cut into 2x2 mm portions”, placement into tissue culture) which is/are considered to reasonably fulfill administering a physical stress, more specifically a mechanical stress, recited at a high level of generality.
Roco-Rivada et al taught wherein the method comprises administering a physical stress, more specifically a mechanical stress, to the biological sample prior to the incubating step (e.g. pg 5416, col. 2, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle tissues….removed”, “tissues were processed”, “muscle pieces were incubated…”, placement into tissue culture), which is/are considered to reasonably fulfill administering a physical stress, more specifically a mechanical stress, recited at a high level of generality.
Wang et al taught wherein a step of administering a physical stress to the biological sample occurs prior to incubation in step (b),
wherein the physical stress comprises a mechanical stress (e.g. pg 3, col. 2, Methods, Primary cells, “minced”, “subculture”; pg 3, col. 2, Methods, Cyclic Stretch, “seeded”).
Guo et al taught wherein a step of administering a physical stress to the biological sample occurs prior to incubation in step (b),
wherein the physical stress comprises a mechanical stress (e.g. pg 2502, col. 1, Methods, Cell Seeding, “trypsinization”, “suspended”, “seeded”).
With respect to Claim 17, Loppnow et al taught wherein the biological sample is from a human donor subject (e.g. pg 732, col. 1, Methods, human saphenous veins).
Wang et al taught wherein the biological sample is from a human donor subject (e.g. pg 3, col. 1, Methods, Primary cells, “human… obtained from clinically healthy patients”).
Guo et al taught wherein the biological sample comprises tissue or isolated cells, wherein the biological sample comprises a single type of isolated cells and is substantially free of other types of tissue (e.g. pg 2501, col. 1, Methods, Cell culture “primary human skeletal muscle cells”).
With respect to Claims 7-8, Loppnow et al taught wherein the biological sample tissue comprises saphenous vein tissue comprising smooth muscle cells (e.g. pg 732, col. 1, Methods, human saphenous veins).
Roco-Rivada et al taught wherein the biological sample tissue comprises muscle (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle pieces were incubated…”).
Wang et al taught wherein the biological sample comprises tissue or isolated ligament cells, wherein the biological sample comprises a single type of isolated cells and is substantially free of other types of tissue (e.g. pg 2, col. 2, Methods, Cell lines; pg 3, col. 1, Methods, Primary cells, “human… obtained from clinically healthy patients”).
Guo et al taught wherein the biological sample comprises tissue or isolated cells, wherein the biological sample comprises a single type of isolated cells and is substantially free of other types of tissue (e.g. pg 2501, col. 1, Methods, Cell culture “primary human skeletal muscle cells”).
With respect to Claim 23, Loppnow et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pg 732, col. 1, Methods, human saphenous veins).
Roco-Rivada et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing).
Wang et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pg 3, col. 2, Methods, Cyclic Stretch).
Guo et al taught wherein the extraction solution comprises a cell culture medium comprising serum and a buffered solution (which necessarily comprises a salt) (e.g. pg 2502, col. 1, Methods, Cell Seeding, “growth medium”).
With respect to Claim 25, Loppnow et al taught wherein the incubating step comprises soaking the biological sample in an extraction solution for a period of 24 hours (e.g. pg 732, col. 1, Methods, human saphenous veins, “was added for 24h”). Those of ordinary skill in the art would have reasonably understood that the culture conditions are performed at least at room temperature (syn. 25C) or 37C, as such is routine practice in the art.
Roco-Rivada et al taught wherein the incubating step comprises soaking the biological sample in an extraction solution for a period of 12 hours (e.g. pg 5417, col. 1, Methods, 2.2 Muscle tissue secretome collection and processing, “incubated for 12h”). Those of ordinary skill in the art would have reasonably understood that the tissue culture conditions are performed at least at room temperature (syn. 25C) or 37C, as such is routine practice in the art.
Wang et al taught wherein the incubating step comprises soaking the biological sample in an extraction solution for a period of 24 hours (e.g. pg 3, col. 2, Methods, Cyclic Stretch, “incubated for 24h”, “10 cycles/min for 24h”). Those of ordinary skill in the art would have reasonably understood that the tissue culture conditions are performed at least at room temperature (syn. 25C; e.g. pg 4, col. 1, Methods, “cultured at room temperature”) or 37C (e.g. pg 4, col. 2, Methods, “exosomes at 37C”; Figure 6, legend, “exosomes at 37C”), as such is routine practice in the art.
Guo et al taught wherein the incubating step comprises soaking the biological sample in an extraction solution for a period of 48 hours (e.g. pg 2502, col. 1, Methods, Mechanical Stimulation, “cyclic stretch was applied for 2 days before EV extraction”). Those of ordinary skill in the art would have reasonably understood that the tissue culture conditions are performed at least at room temperature (syn. 25C) or 37C (e.g. pg 2502, col. 2, Methods, “37C”), as such is routine practice in the art.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
Instant specification fails to disclose an element of criticality for the temperature limitation “2C to 42C”, as it pertains to a method of producing an enriched tissue extract from a primary biological sample obtained from a donor and as compared to the tissue culture temperatures of the cited prior art.
With respect to Claim 27, Loppnow et al taught wherein the separating step comprises separating the enriched tissue extract from the biological sample using at least centrifugation (e.g. pg 732, col. 1, Methods, “supernatants were harvested and centrifuged”).
Roco-Rivada et al taught wherein the separating step comprises separating the enriched tissue extract from the biological sample using at least centrifugation (e.g. pg 5417, col. 1, Methods, 2.2 Muscle tissue secretome collection and processing, “Secretomes were immediately processed….by ultracentrifugation”).
Wang et al taught wherein the separating step comprises separating the enriched tissue extract from the biological sample using at least centrifugation (e.g. pg 3, col. 2, Methods, Cyclic Stretch, “prepared by centrifugation”; Isolation of Exosomes, “centrifugation”).
Guo et al taught wherein the separating step comprises separating the enriched tissue extract from the biological sample using at least centrifugation (e.g. pg 2502, col. 1, Methods, EV isolation, “performed using differential centrifugation”, “ultracentrifuged”).
With respect to Claim 28, the term "comprising", per “the tissue extract comprises…”, is open-ended and allows for additional, unrecited elements in the claimed tissue extract. MPEP 2111.03 specifically sets forth that the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Loppnow et al taught wherein enriched tissue extract comprises signaling molecules such as IL-6, amino acids, and growth factor proteins (e.g. Figure 4), as there is no objective evidence of record that the step of centrifuging the culture supernatant at 1,500g (pg 732, col. 1, Methods, “supernatants were harvested and centrifuged”) physically removes and separates IL-6 from other extract components such as growth factor proteins and/or other signaling molecules, per natural law(s) of biology, chemistry and physics, and per the logic of the claimed limitations recited at a high level of generality.
Roco-Rivada et al taught wherein enriched tissue extract comprises signaling molecules such as IL-6, amino acids, and growth factor proteins (e.g. pg 5417, col. 2, “myokine (IL-6)”; “161 proteins”; Figure 2; Tables 1-3), as there is no objective evidence of record that the step of centrifuging the culture supernatant physically removes and separates IL-6 from other extract components such as growth factor proteins and/or other signaling molecules, per natural law(s) of biology, chemistry and physics, and per the logic of the claimed limitations recited at a high level of generality.
Wang et al taught wherein the enriched tissue extract comprises one or more of exosomes (e.g. pg 3, col.2, Methods, Exosome isolation).
Guo et al taught wherein the enriched tissue extract comprises one or more of exosomes (e.g. 2497, col. 1, “extracellular vesicles (EVs), including exosomes”).
Since the Patent Office does not have the laboratory facilities for examining and comparing Applicants' tissue extract recited at a high level of generality with the tissue extract(s) of the prior art reference(s), the burden is upon Applicants to show a distinction between the material structural and functional characteristics of the claimed tissue extract and the tissue extract(s) of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Response to Arguments
Applicant argues that Wang is directed to isolated ligament cells from minced tissues, which is differ
Applicant’s argument(s) has been fully considered, but is not persuasive.
As a first matter, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Loppnow et al taught wherein the biological sample tissue comprises saphenous vein tissue comprising smooth muscle cells (e.g. pg 732, col. 1, Methods, human saphenous veins).
Roco-Rivada et al taught wherein the biological sample tissue comprises muscle (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle pieces were incubated…”). As a second matter, the Examiner must determine what is "analogous prior art" for the purpose of analyzing the obviousness of the subject matter at issue. **>"Under the correct analysis, any need or problem known in the field of endeavor at the time of the invention and addressed by the patent [or application at issue] can provide a reason for combining the elements in the manner claimed. " KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). Thus a reference in a field different from that of applicant's endeavor may be reasonably pertinent if it is one which, because of the matter with which it deals, logically would have commended itself to an inventor's attention in considering his or her invention as a whole.<
Independent Claim 1 recites the biological sample tissue at a high level of generality.
Loppnow et al taught a method of producing an enriched tissue extract from a biological tissue sample, the method comprising a step of applying a stimulus to the tissue prior to obtaining the enriched tissue extract (e.g. pg 734, col. 2, “short-term organoid cultures of human saphenous veins….stimulus”).
Roco-Rivada et al taught method of producing an enriched tissue extract from a biological tissue sample, muscle tissue secretome using cultured muscle tissues (e.g. pg 5415, col. 2, “2.2 Muscle tissue secretome collection and processing”), comparing the secretome of muscle tissue before and after exercise (syn. mechanical stress) (e.g. Abstract, “variation after exercise intervention”).
Wang et al taught method of producing an enriched tissue extract from a biological tissue sample, the method comprising the step of applying cyclic stretch to a tissue of confluent cells, whereby cyclic stretching (syn. mechanical stress) of the tissue changes the molecular profile of the secretome (e.g. pg 5, col. 2, “Cyclic Stretch Induces…Cells to Secrete…”), including the secretion of exosomes (e.g. pg 7, col. 1, “Cyclic Stretch Induces…to Secrete Exosomes”). Wang et al taught “We demonstrated that cyclic stretch, which mimics the physiological mechanical environment… induces… cells to secrete exosomes” (e.g. pg 12, Discussion topic sentence).
Applicant argues that Guo is directed to fabricated tissues using isolated myoblast cell lines.
Applicant’s argument(s) has been fully considered, but is not persuasive.
As a first matter, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Loppnow et al taught wherein the biological sample tissue comprises saphenous vein tissue comprising smooth muscle cells (e.g. pg 732, col. 1, Methods, human saphenous veins).
Roco-Rivada et al taught wherein the biological sample tissue comprises muscle (e.g. pgs 5416-5417, joining para, Methods, 2.2 Muscle tissue secretome collection and processing; “muscle pieces were incubated…”). As a second matter, the Examiner must determine what is "analogous prior art" for the purpose of analyzing the obviousness of the subject matter at issue. **>"Under the correct analysis, any need or problem known in the field of endeavor at the time of the invention and addressed by the patent [or application at issue] can provide a reason for combining the elements in the manner claimed. " KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). Thus a reference in a field different from that of applicant's endeavor may be reasonably pertinent if it is one which, because of the matter with which it deals, logically would have commended itself to an inventor's attention in considering his or her invention as a whole.<
Independent Claim 1 recites the biological sample tissue at a high level of generality.
Loppnow et al taught a method of producing an enriched tissue extract from a biological tissue sample, the method comprising a step of applying a stimulus to the tissue prior to obtaining the enriched tissue extract (e.g. pg 734, col. 2, “short-term organoid cultures of human saphenous veins….stimulus”).
Roco-Rivada et al taught method of producing an enriched tissue extract from a biological tissue sample, muscle tissue secretome using cultured muscle tissues (e.g. pg 5415, col. 2, “2.2 Muscle tissue secretome collection and processing”), comparing the secretome of muscle tissue before and after exercise (syn. mechanical stress) (e.g. Abstract, “variation after exercise intervention”).
Guo et al taught method of producing an enriched tissue extract from a biological tissue sample, the method comprising the step of applying cyclic stretch to an engineered tissue comprising skeletal muscle cells, whereby cyclic stretching (syn. mechanical stress) of the tissue changes the molecular profile of the secretome, including the secretion of exosomes (e.g. Title).
Guo et al taught that current extracellular vesicle production from cells relies heavily on 2D cell culture, which is not only less physiologically relevant to cells, but also requires substantial culture medium and space. However, by applying mechanical forces, including agitation, extracellular vesicle production is significantly enhanced (e.g. Abstract).
Conclusion
14. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
Prosecution Insights