Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 7, 2026 has been entered.
Detailed Action
This action is in response to the papers filed January 7, 2026.
Amendments
Applicant's response and amendments, filed December 5, 2025 and January 7, 2026, are acknowledged. Applicant has cancelled Claims 1-12, amended Claims 13, 15, and 22, and withdrawn Claims 16-21.
Claims 13-24 are pending.
Election/Restrictions
Applicant has elected without traverse the following species, wherein:
i) the alternative means by which the fibroblasts are de-differentiated into pluripotent cells is cell programming, as recited in Claims 14 (cell programming), and
ii) the alternative additional method step is the cells are rendered substantially free of immunogenic proteins by incubating the cells for a period of time in protein-free medium, as recited in Claim 22.
Claims 13-24 are pending.
Claims 16-21 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.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 13-15 and 22-24 are under consideration.
Priority
This application is a continuation of application 13/941,265 filed July 12, 2013, now U.S. Patent 11,554,142, which is a continuation of application 12/776,163 filed May 7, 2010, now U.S. Patent 8,529,883.
This application repeats a substantial portion of prior Application No. 13/941,265 filed July 12, 2013, now U.S. Patent 11,554,142, and Application No. 12/776,163 filed May 7, 2010, now U.S. Patent 8,529,883, and adds disclosure not presented in the prior application. Because this application names the inventor or at least one joint inventor named in the prior application, it may constitute a Continuation-In-Part of the prior application. Should applicant desire to claim the benefit of the filing date of the prior application, attention is directed to 35 U.S.C. 120, 37 CFR 1.78, and MPEP § 211 et seq. The presentation of a benefit claim may result in an additional fee under 37 CFR 1.17(w)(1) or (2) being required, if the earliest filing date for which benefit is claimed under 35 U.S.C. 120, 121, 365(c), or 386(c) and 1.78(d) in the application is more than six years before the actual filing date of the application.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application 13/941,265 filed July 12, 2013, and application 12/776,163 filed May 7, 2010 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
With respect to Claim 13, the claim has been amended (September 3, 2025) to recite a method of producing pluripotent cells for tissue repair or regeneration, the method comprising the step(s) of:
a) providing a dosage formulation comprising between 1.0 x 10^7 and 2.7 x 10^7 cells/mL,
wherein at least 98% of the cells are autologous human fibroblast cells or precursors thereof, at least 85% of which are viable, and
b) de-differentiating the cells.
With respect to Claim 22, the specification is silent to the phrase “sufficient to achieve the reduction…”. The specification is silent to the step of removing the spent medium and washing the cells, thereby producing a population of pluripotent cells rendered substantially free of immunogenic proteins.
While [0048] discloses culturing autologous dermal fibroblasts for a period of time in protein-free medium, [0048] is silent to the step of removing the spent medium and washing the cells, thereby producing a population of pluripotent cells rendered substantially free of immunogenic proteins, let alone that said resulting cells also comprise at least 1x10^7 cells comprising at least 1x10^7 autologous human fibroblasts, of which at least 85% are viable, and de-differentiating said cell population substantially free of immunogenic proteins into a population of pluripotent cells.
United States Court of Appeals for the Federal Circuit, Regents of the University of Minnesota v. Gilead Sciences, Inc (Case 21-2168; decided March 6, 2023).
Written description of a broad genus requires description not only of the outer limits of the genus but also of either a representative number of members of the genus or structural features common to the members of the genus, in either case with enough precision that a relevant artisan can visualize or recognize the members of the genus. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350−52 (Fed. Cir. 2010) (en banc). A broad outline of a genus’s perimeter is insufficient. See id.
Original disclosure may not be relied upon unless it “constitute[s] a full, clear, concise and exact description” of the invention claimed in the pa-tent to one of ordinary skill. In re Wertheim, 646 F.2d 527, 538–39 (CCPA 1981).
For genus claims, which are present here, we have looked for blaze marks within the disclosure that guide attention to the claimed species or subgenus. In re Ruschig, 379 F.2d 990, 994–95 (CCPA 1967); Fujikawa v. Wattana-sin, 93 F.3d 1559, 1571 (Fed. Cir. 1996); see also Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1326–27 (Fed. Cir. 2000).
Following this maze-like path, each step providing multiple alternative paths, is not a written description of what might have been described if each of the optional steps had been set forth as the only option. This argument calls to mind what Yogi Berra, the Yankee catcher, was reported to have said: “when one comes to a fork in the road, take it.” That comment was notable because of its indeterminacy, its lack of direction. Similarly, here, all those optional choices do not define the intended result of the instant combination of specific method step parameters.
As explained by the Board, “[t]hese blaze marks must be clear because ‘it is easy to bypass a tree in the forest, even one that lies close to the trail.’” Decision at *10 (citing Fujikawa, 93 F.3d at 1571).
The Board concluded that, “[i]n this case, we find the point at which one must leave the trail to find the tree is not well marked in [prior application’s 12/776,163, prior application’s 13/941,265, and instant application’s disclosures]. Thus, [12/776,163, 13/941,265, and instant application] do not provide sufficient written description support for the sub-genus of challenged claim 1.” Decision at *10.
While it is clear that the specification discloses that skin-derived fibroblasts can be de-differentiated using epigenetic reprogramming into pluripotent stem cells (e.g. pg 6, lines 30-31), none of the instant application, prior application 13/941,265 and prior application 12/776,163 provide ipsis verbis support nor sufficient blaze marks to guide the skilled artisan to the instantly recited step (a) in a method of producing pluripotent cells.
None of the instant application, prior application 13/941,265 and prior application 12/776,163 provide ipsis verbis support nor sufficient blaze marks to guide the skilled artisan to the instantly recited Claims 18 and 20-24 in a method of producing pluripotent cells.
Applicant’s Remarks Made in Amendment, papers filed February 28, 2023, fail to properly identify where support for the presently amended claimed invention is found in the originally filed specification, claims, and/or drawings.
Applicant does not indicate where these limitations are supported by the original specification, or how, as is Applicant's burden. See MPEP §714.02, last sentence of the third paragraph from the end and MPEP §2163.06 (I) last sentence.
Accordingly, the effective priority date of the instant claims is granted as December 12, 2022, the effective filing date of the instant application.
If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by page and line number in the reply to this Action.
Response to Arguments
Applicant argues that the Examiner has not pointed to the additional disclosure of the instant application not present in the prior documents.
Applicant’s argument(s) has been fully considered, but is not persuasive. The additional disclosure(s) are the instantly claimed limitations of, at least, independent Claim 13, introduced February 28, 2023, which is/are the subject of the New Matter rejection discussed in prior Office Actions and below.
Applicant argues that support for the amended claims is found in [0038-40, 42-51, and 53].
Applicant’s argument(s) has been fully considered, but is not persuasive. The Examiner refers to U.S. 2023/0270793 (U.S. PGPub of instant application), as originally filed specification fails to provide corresponding paragraph numbers.
[0038-40] is/are silent to the recited limitations of independent Claim 13.
[0042-48] is/are silent to the recited limitations of independent Claim 13.
While [0049] discloses a formulation of at least 3.4x10^8 cells, such is silent to that formulation comprising at least 98% autologous fibroblasts, at least 85% of which are viable, and the method step of de-differentiating said formulation.
[0050-51] is/are silent to the recited limitations of independent Claim 13.
While [0053] discloses a formulation of at least 1.0-2.7x10^7 cells/ml, such is silent to that formulation comprising at least 98% autologous fibroblasts, at least 85% of which are viable, and the method step of de-differentiating said formulation.
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.
1. The prior rejection of Claim 22 under 35 U.S.C. 101 is withdrawn in light of Applicant’s amendment to the claim to recite the step of incubating the cells in a protein-free medium, which the Examiner finds persuasive.
2. Claim 15 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) a pluripotent cell formulation.
With respect to Step 1, the claim is directed to a product, which is a statutory category of invention (Step 1: YES).
With respect to Step 2A, prong one, the judicial exception, the claim is direct to a pluripotent cell formulation, whereby pluripotent cells are naturally occurring cells. For example, Young et al (Pluripotent Stem Cells, Endogenous versus Reprogrammed, a Review, MOJ Orthopedics & Rheumatology, 1(3): e00019, 20 pages, DOI: 10.15406/mojor.2014.01.00019; November 26, 2014) is considered relevant art for having taught that the art recognizes pluripotent cells to be naturally occurring cells in animals (e.g. pg 3, col. 1, “can be seen as early as morula stage in human embryonic development”; pg 12, col. 1, “a sufficient number of separate laboratories have proven that endogenous pluripotent stem cells do exist and can be readily isolated, characterized, and utilized”). The claim is directed to a judicial exception (Step 2A, prong one: YES).
With respect to Step 2A, prong two, the claim does not recite additional elements that integrate the judicial exception into a practical application. The recitation of a process limitation in Claim 15, referring back to Claim 13, is not viewed as positively limiting the claimed product absent a showing that the process of making imparts a novel or unexpected property to the claimed product as it is assumed that equivalent products of pluripotent cells produced by de-differentiating autologous human fibroblasts are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed pluripotent cell product and referenced pluripotent cell product. The method in which the pluripotent cell product were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113. The claim does not integrate the judicial exception into a practical application (Step 2A, prong two: NO).
With respect to Step 2B, isolation of pluripotent stem cells does not change the cells in any way. The claim is not considered to recite additional elements that amount to significantly more than the judicial exception itself (Step 2B: NO).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
3. The prior rejection of Claim 22 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in light of Applicant’s amendment to the claim to recite the step of incubating the cells in a protein-free medium, which the Examiner finds persuasive.
New matter
4. Claim(s) 13-15 and 22-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 13 recites a method of producing pluripotent cells for tissue repair or regeneration, the method comprising the step(s) of:
a) providing a dosage formulation comprising between 1.0 x 10^7 and 2.7 x 10^7 cells/mL,
wherein at least 98% of the cells are autologous human fibroblast cells or precursors thereof, at least 85% of which are viable, and
b) de-differentiating the cells.
Clear support for the new limitation(s) cannot be found in the instant application or priority documents.
Accordingly, the amendment(s) to the claims are considered to constitute new matter.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application”. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
United States Court of Appeals for the Federal Circuit, Regents of the University of Minnesota v. Gilead Sciences, Inc (Case 21-2168; decided March 6, 2023).
Written description of a broad genus requires description not only of the outer limits of the genus but also of either a representative number of members of the genus or structural features common to the members of the genus, in either case with enough precision that a relevant artisan can visualize or recognize the members of the genus. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350−52 (Fed. Cir. 2010) (en banc). A broad outline of a genus’s perimeter is insufficient. See id.
Original disclosure may not be relied upon unless it “constitute[s] a full, clear, concise and exact description” of the invention claimed in the patent to one of ordinary skill. In re Wertheim, 646 F.2d 527, 538–39 (CCPA 1981).
For genus claims, which are present here, we have looked for blaze marks within the disclosure that guide attention to the claimed species or subgenus. In re Ruschig, 379 F.2d 990, 994–95 (CCPA 1967); Fujikawa v. Wattana-sin, 93 F.3d 1559, 1571 (Fed. Cir. 1996); see also Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1326–27 (Fed. Cir. 2000).
Following this maze-like path, each step providing multiple alternative paths, is not a written description of what might have been described if each of the optional steps had been set forth as the only option. This argument calls to mind what Yogi Berra, the Yankee catcher, was reported to have said: “when one comes to a fork in the road, take it.” That comment was notable because of its indeterminacy, its lack of direction. Similarly, here, all those optional choices do not define the intended result of the instant combination of specific method step parameters.
As explained by the Board, “[t]hese blaze marks must be clear because ‘it is easy to bypass a tree in the forest, even one that lies close to the trail.’” Decision at *10 (citing Fujikawa, 93 F.3d at 1571).
The Board concluded that, “[i]n this case, we find the point at which one must leave the trail to find the tree is not well marked in [prior application’s 12/776,163, prior application’s 13/941,265, and instant application’s disclosures]. Thus, [12/776,163, 13/941,265, and instant application] do not provide sufficient written description support for the sub-genus of challenged claim 1.” Decision at *10.
While it is clear that the specification discloses that skin-derived fibroblasts can be de-differentiated using epigenetic reprogramming into pluripotent stem cells (e.g. pg 6, lines 30-31), none of the instant application, prior application 13/941,265 and prior application 12/776,163 provide ipsis verbis support nor sufficient blaze marks to guide the skilled artisan to the instantly recited steps (a) providing, and (b) de-differentiating, in a method of producing pluripotent cells.
None of the instant application, prior application 13/941,265 and prior application 12/776,163 provide ipsis verbis support nor sufficient blaze marks to guide the skilled artisan to the instantly recited Claim 22 step of rendering the induced pluripotent cells substantially free of immunogenic proteins by incubating the cells for a period of time in protein-free medium in a method of producing pluripotent cells.
Claim 22 recites the broad recitation “substantially free….. of immunogenic proteins”, which is a relative term, and the claim also recites “reduced in an amount relative to the amount present prior to incubation”, which is also a relative term, and which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The specification is silent to the phrase “sufficient to achieve the reduction…”.
The specification is silent to the step of removing the spent medium and washing the cells, thereby producing a population of pluripotent cells rendered substantially free of immunogenic proteins.
Applicant’s Remarks Made in Amendment, papers filed February 28, 2023, fail to properly identify where support for the presently amended claimed invention is found in the originally filed specification, claims, and/or drawings.
Applicant’s Remarks Made in Amendment, papers filed April 9, 2025, fail to properly identify where support for the presently amended claimed invention is found in the originally filed specification, claims, and/or drawings.
Applicant does not indicate where these limitations are supported by the original specification, or how, as is Applicant's burden. See MPEP §714.02, last sentence of the third paragraph from the end and MPEP §2163.06 (I) last sentence.
Accordingly, the effective priority date of the instant claims is granted as December 12, 2022, the effective filing date of the instant application.
If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by page and line number in the reply to this Action.
Response to Arguments
Applicant argues that the instantly recited limitations are disclosed in the specification [0038-41, and 43-51].
Applicant’s argument(s) has been fully considered, but is not persuasive.
[0040] discloses that fibroblasts can be de-differentiated into iPS cells. [0040] does not disclose the use of the claimed dosage formulation to be de-differentiated into iPS
[0041] refers to Figure 3, which merely illustrates different means by which reprogramming factors can be introduced into a somatic cell [generic]. [0041] does not disclose the use of the claimed dosage formulation to be de-differentiated into iPS
[0043-51] is/are directed to obtaining autologous fibroblasts, not de-differentiating the instantly recited drug formulation.
5. Claims 13-15 and 22-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
As a first matter, the phrase “a dosage formulation…. comprising at least 98% autologous human fibroblasts…. in a therapeutic effective amount” in Claim 13 is/are a relative term(s) which renders the claim indefinite. The phrases “dosage formulation” and “therapeutic effective amount” is/are an intended use, not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The phrase “a dosage formulation” begs the question: A dosage formulation for what?
The phrase “therapeutic effective amount” begs the question: Therapeutic effective for what?
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. (See MPEP §2114.)
The phrase “a dosage formulation” is considered to render the claim indefinite because that which is vs is not “a dosage formulation” is considered an arbitrary and subjective determination.
As a second matter, the phrase “a dosage formulation…. 1x10^7 to 2.7x10^7 cells/mL” in Claim 13 is a relative term which renders the claim indefinite. While it is clear that the dosage formulation of autologous human fibroblasts, or precursors thereof, are to be at a concentration of about 1x10^7 to 2.7x10^7 cells/mL, the claim fails to recite the actual volume of said dosage formulation, and thus also fails to recite the actual number of cells that are to be de-differentiated. The claims and specification do not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The specification discloses, for example, each tube contains 1x10^5 viable cells (e.g. pg 13, line 20), e.g. a 7uL aliquot of a 1.5x10^7 cells/mL concentration (e.g. pg 13, line 25).
The specification also discloses, for example, an amount of 100ul or 200ul (e.g. pg 23, lines 6-7), which is equivalent to about 1x10^6 cells.
The specification also discloses, for example, an amount of 2mL (e.g. pg 23, line 22), which is equivalent to about 2x10^7 to 5.4x10^7 cells.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The instantly recited cell concentration is uninformative as to the number of cells that are to be de-differentiated in the claimed method.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Response to Amendment
Applicant argues that the number of cells provides the ordinary artisan with the information needed to carry out the claimed method.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant fails to clarify the record and/or amend the claims to render the prior issues moot.
6. Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
As a first matter, the phrase “substantially free” in Claim 22 is a relative term which renders the claim indefinite. The phrase “substantially free” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The phrase denotes that there is an amount of immunogenic proteins present in the pluripotent cell composition culture medium which may or may not be interpreted to fall within “substantially free” or is outside the scope of “substantially free”. Rather, “substantially free” is considered an arbitrary and subjective determination.
As a second matter, the phrase “for a period of time” in Claim 22 is a relative term which renders the claim indefinite. The phrase “for a period of time” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The phrase denotes that there is an amount of time of incubation during which the culture medium may or may not be interpreted to fall within “substantially free of immunogenic proteins” or is outside the scope of “substantially free of immunogenic proteins”. Rather, period of time… substantially free of immunogenic proteins” is considered an arbitrary and subjective determination.
The specification is silent to the phrase “sufficient to achieve the reduction…”.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Response to Arguments
Applicant argues that “substantially free” means a significant reduction, not an absolute absence, of immunogenic proteins.
Applicant’s argument(s) has been fully considered, but is not persuasive. Instant specification fails to disclose a definition of what does/does not objectively constitute “substantially free of immunogenic proteins”. The amount of immunogenic proteins that may or may not be present is considered an arbitrary and subjective determination.
Instant specification fails to disclose, and instant Claim 22 fails to recite, the amount of time in which the cells are to be cultured in protein-free medium to thereby achieve the “substantially free…of immunogenic proteins”. The “period of time sufficient” that must be performed is considered an arbitrary and subjective determination.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
7. Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claim recites “wherein the cells are rendered substantially free of immunogenic proteins”. There is insufficient antecedent basis for this limitation in the claim because Claim 13 recites two different cell populations:
i) the autologous human fibroblasts; and
ii) the pluripotent cells.
To which cell population does Applicant refer in Claim 22?
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
8. Claims 13-15 and 22-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 has been amended to recite the limitation “wherein…. are autologous human fibroblast cells reactive with a cell surface marker for fibroblasts and not with a cell surface marker for keratinocyte cells”.
The recitation implies a genus of unrecited cell surface markers for fibroblasts that may or may not be present, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
If there are multiple cell surface markers for fibroblasts, yet each yields a different result, then the claim may be indefinite because it is unclear which cell surface marker is to be is to be expressed by the autologous human fibroblasts to determine infringement.
The recitation implies a genus of unrecited cell surface markers for keratinocytes that may or may not be absent, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
If there are multiple cell surface markers for keratinocytes, yet each yields a different result, then the claim may be indefinite because it is unclear which cell surface marker is to be is to be not expressed by the autologous human fibroblasts to determine infringement.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
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 pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
9. The prior rejection of Claim(s) 13-15 and 22 under pre-AIA 35 U.S.C. 102(b) as being anticipated by Takahashi et al (2007; of record in IDS), as evidenced by Biological Industries (last visited July 28, 2016; of record) is withdrawn in light of Applicant’s amendment to independent Claim 13 to recite the autologous human fibroblast cells are reactive with a fibroblast cell marker, but not with a keratinocyte cell marker, a limitation Takahashi et al do not teach.
10. Claim(s) 15 is rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Lowry et al (2008; of record).
With respect to Claim 15, Lowry et al is considered relevant prior art for having taught a pluripotent cell formulation prepared by de-differentiating a population of autologous human fibroblasts (e.g. Abstract, “to use dermal fibroblasts easily obtained from an individual human”; pg 2883, col. 2, Results, “human fibroblasts donated from...”).
Lowry et al do not teach wherein the pluripotent cell formulation was prepared by de-differentiating a dosage formulation comprising 1x10^7 to 2.7x10^7 cells/mL of the primary human autologous fibroblasts, at least 85% of which are viable.
However, the recitation of a process limitation in Claim 15, referring back to Claim 13, is not viewed as positively limiting the claimed product absent a showing that the process of making imparts a novel or unexpected property to the claimed product as it is assumed that equivalent products of pluripotent cells produced by de-differentiating autologous human fibroblasts are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed pluripotent cell product and referenced pluripotent cell product. The method in which the pluripotent cell product were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
Thus, Lowry et al anticipate the claim(s).
Response to Arguments
Applicant argues that the features of cell purity and concentration recited in Claim 15 required a great deal of experimentation.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant’s argument is not on point.
As discussed in the prior Office Action, the recitation of a process limitation in Claim 15, referring back to Claim 13, is not viewed as positively limiting the claimed product absent a showing that the process of making imparts a novel or unexpected property to the claimed product as it is assumed that equivalent products of pluripotent cells produced by de-differentiating autologous human fibroblasts are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed pluripotent cell product and referenced pluripotent cell product. The method in which the pluripotent cell product were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
Applicant fails to provide objective evidence that the instantly claimed pluripotent cells are structurally and/or functionally distinct from the pluripotent cells of Lowry et al.
11. Claim(s) 13-15 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Maherli et al (A High-Efficiency System for the Generation and Study of Human Induced Pluripotent Stem Cells, Cell Stem Cell 3: 340-345, 2008), as evidenced by Shamis et al (iPSC-derived fibroblasts demonstrate augmented production and assembly of extracellular matrix proteins, In Vitro Cell. Dev. Biol.—Animal 48: 112-122, 2012).
With respect to Claim 13, Maherli et al is considered relevant prior art for having taught a method of producing pluripotent stem cells from primary human fibroblasts (syn. autologous human fibroblasts; e.g. pg 340, col. 2, Results, “BJ fibroblasts”), the method comprising the step of de-differentiating a population of about 2.5x10^5 primary human fibroblasts (e.g. pg 342, col. 1-2, joining para; Figure 1).
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase "for injection into humans" is an intended use limitation, which does not contain any further structural limitations with respect to claimed pharmaceutical preparation comprising 1x10^7 to 2.7x10^7 cells/ml (see MPEP §2114).
As discussed above in the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection, the phrase “a dosage formulation for injection into humans…. 1x10^7 to 2.7x10^7 cells/mL” renders the claim indefinite. While it is clear that the dosage formulation of autologous human fibroblasts, or precursors thereof, are to be at a concentration of about 1x10^7 to 2.7x10^7 cells/mL, the claim fails to recite the actual volume of said dosage formulation, and thus actual number of cells that are to be de-differentiated. The instantly recited cell concentration is uninformative as to the number of cells that are to be de-differentiated in the claimed method.
The specification discloses, for example, each tube contains 1x10^5 viable cells (e.g. pg 13, line 20), e.g. a 7uL aliquot of a 1.5x10^7 cells/mL concentration (e.g. pg 13, line 25).
Maherli et al taught the step of de-differentiating a population of about 2.5x10^5 primary human fibroblasts, and thus is considered to reasonably fulfill the instant recitation.
Maherli et al do not teach ipsis verbis wherein…. are autologous human fibroblast cells reactive with a cell surface marker for fibroblasts and not with a cell surface marker for keratinocyte cells.
However, Shamis et al is considered relevant prior art for having taught that the BJ fibroblast cells of Maherli et al inherently and naturally express CD90, “known to be characteristic of stromal fibroblasts” (e.g. pg 118, col. 2). The instant specification discloses CD90 to be a fibroblast-specific marker (e.g. [0038]).
Neither Maherli et al nor Shamis et al teach ipsis verbis that the fibroblasts expressing a fibroblast-specific marker CD90 do not express a keratinocyte cell surface marker. However, those of ordinary skill in the art would reasonably infer and understand that said CD90+ fibroblast would not be expressing a keratinocyte cell surface marker because said CD90 expression is “fibroblast-specific”, as admitted by Applicant.
Instant specification fails to disclose a population of primary dermal fibroblasts that while being positive for a fibroblast cell surface marker, e.g. CD90, an art-recognized and Applicant-admitted “fibroblast-specific” cell surface marker, still express a keratinocyte cell surface marker. Rather, the ordinary artisan would have reasonably understood that it is natural law of cell biology that keratinocyte cell surface markers would not be present in said population of CD90+ primary dermal fibroblasts because they are fibroblasts, not keratinocytes.
With respect to Claim 14, Maherli et al taught wherein the cells are de-differentiated by cell programming, to wit, the Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc (e.g. pg 340, Summary, Results).
With respect to Claim 15, Maherli et al taught a pluripotent cell formulation prepared by de-differentiating a population of autologous human fibroblasts prepared by the method.
As discussed above, the recitation of a process limitation in Claim 15, referring back to Claim 13, is not viewed as positively limiting the claimed product absent a showing that the process of making imparts a novel or unexpected property to the claimed product as it is assumed that equivalent products of pluripotent cells produced by de-differentiating autologous human fibroblasts are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed pluripotent cell product and referenced pluripotent cell product. The method in which the pluripotent cell product were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
Thus, Maherli et al anticipate the claims.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
12. Claim(s) 13-15 and 22 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Takahashi et al (2007; of record) in further view of Maherli et al (2008; of record), Shamis et al (2012; of record), and Kucharski et al (Current standards and pitfalls associated with the transfection of primary fibroblast cells, Biotechnol. Progress 37: e3152, 10 pages, DOI: 10.1002/btpr.3152; available online March 28, 2021).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
As discussed above, the effective priority date of the instant claims is granted as December 12, 2022, the effective filing date of the instant application.
With respect to Claim 13, Takahashi et al is considered relevant prior art for having taught a method of producing pluripotent stem cells from primary human fibroblasts (syn. autologous human fibroblasts; e.g. pg 869, col. 1, Experimental Procedures, Cell Culture), the method comprising the step of de-differentiating a population of at least 5x10^5 primary human fibroblasts (e.g. pg 862, col. 1).
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase "for injection into humans" is an intended use limitation, which does not contain any further structural limitations with respect to claimed pharmaceutical preparation comprising 1x10^7 to 2.7x10^7 cells/ml (see MPEP §2114).
As discussed above in the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection, the phrase “a dosage formulation for injection into humans…. 1x10^7 to 2.7x10^7 cells/mL” renders the claim indefinite. While it is clear that the dosage formulation of autologous human fibroblasts, or precursors thereof, are to be at a concentration of about 1x10^7 to 2.7x10^7 cells/mL, the claim fails to recite the actual volume of said dosage formulation, and thus actual number of cells that are to be de-differentiated. The instantly recited cell concentration is uninformative as to the number of cells that are to be de-differentiated in the claimed method.
The specification discloses, for example, each tube contains 1x10^5 viable cells (e.g. pg 13, line 20), e.g. a 7uL aliquot of a 1.5x10^7 cells/mL concentration (e.g. pg 13, line 25).
Takahashi et al taught the step of de-differentiating a population of at least 5x10^5 primary human fibroblasts, and thus is considered to reasonably fulfill the instant recitation.
Takahashi et al do not teach wherein the autologous human fibroblast cells are reactive with a fibroblast cell marker, but not with a keratinocyte cell marker.
However, prior to the instantly claimed invention, and with respect to Claim 13, Maherli et al is considered relevant prior art for having taught a method of producing pluripotent stem cells from primary human fibroblasts (syn. autologous human fibroblasts; e.g. pg 340, col. 2, Results, “BJ fibroblasts”), the method comprising the step of de-differentiating a population of about 2.5x10^5 primary human fibroblasts (e.g. pg 342, col. 1-2, joining para; Figure 1).
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The phrase "for injection into humans" is an intended use limitation, which does not contain any further structural limitations with respect to claimed pharmaceutical preparation comprising 1x10^7 to 2.7x10^7 cells/ml (see MPEP §2114).
As discussed above in the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection, the phrase “a dosage formulation for injection into humans…. 1x10^7 to 2.7x10^7 cells/mL” renders the claim indefinite. While it is clear that the dosage formulation of autologous human fibroblasts, or precursors thereof, are to be at a concentration of about 1x10^7 to 2.7x10^7 cells/mL, the claim fails to recite the actual volume of said dosage formulation, and thus actual number of cells that are to be de-differentiated. The instantly recited cell concentration is uninformative as to the number of cells that are to be de-differentiated in the claimed method.
The specification discloses, for example, each tube contains 1x10^5 viable cells (e.g. pg 13, line 20), e.g. a 7uL aliquot of a 1.5x10^7 cells/mL concentration (e.g. pg 13, line 25).
Maherli et al taught the step of de-differentiating a population of about 2.5x10^5 primary human fibroblasts, and thus is considered to reasonably fulfill the instant recitation.
Maherli et al do not teach ipsis verbis wherein…. are autologous human fibroblast cells reactive with a cell surface marker for fibroblasts and not with a cell surface marker for keratinocyte cells.
However, Shamis et al is considered relevant prior art for having taught that the BJ fibroblast cells of Maherli et al inherently and naturally express CD90, “known to be characteristic of stromal fibroblasts” (e.g. pg 118, col. 2). The instant specification discloses CD90 to be a fibroblast-specific marker (e.g. [0038]).
Neither Maherli et al nor Shamis et al teach ipsis verbis that the fibroblasts expressing a fibroblast-specific marker CD90 do not express a keratinocyte cell surface marker. However, those of ordinary skill in the art would reasonably infer and understand that said CD90+ fibroblast would not be expressing a keratinocyte cell surface marker because said CD90 expression is “fibroblast-specific”, as admitted by Applicant.
Nevertheless, Kucharski et al is considered relevant prior art for having taught that establishment of the purity of primary dermal fibroblasts can be confirmed using positive staining of fibroblast marker Thy-1 (syn. CD90) and negative staining of keratinocyte markers, e.g. cytokeratin (e.g. pg 3, col. 1).
Instant specification fails to disclose a population of primary dermal fibroblasts that while being positive for a fibroblast cell surface marker, e.g. CD90, and negative for one or more keratinocyte markers, e.g. cytokeratin(s), still express a keratinocyte cell surface marker. Rather, the ordinary artisan would have reasonably understood that it is natural law of cell biology that keratinocyte cell surface markers would not be present in said population of primary dermal fibroblasts because they are fibroblasts, not keratinocytes.
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, including primary human cells and induced pluripotent stem 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 instantly claimed invention, it would have been obvious to one of ordinary skill in the art to confirm the purity of an established primary human dermal fibroblast population to be used in a method of producing pluripotent cells selecting for primary human dermal fibroblasts that express a fibroblast marker, e.g. CD90 (syn. Thy-1) and do not express a keratinocyte marker, e.g. cytokeratin, with a reasonable expectation of success because those of ordinary skill in the art had previously recognized and successfully reduced to practice the ability to produce pluripotent cells from primary human fibroblasts that express a fibroblast marker, e.g. CD90 (syn. Thy-1) and do not express a keratinocyte marker (e.g. Maherli et al), whereby the purity of said primary human fibroblasts is readily confirmed using fibroblast-specific markers and not keratinocyte-specific markers.
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 14, Takahashi et al taught wherein the cells are de-differentiated by cell programming, to wit, the Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc (e.g. Abstract).
Maherli et al taught wherein the cells are de-differentiated by cell programming, to wit, the Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc (e.g. pg 340, Summary, Results).
With respect to Claim 22, Takahashi et al taught wherein the pluripotent cells were cultured in a culture medium comprising DMEM/F12 and knockout serum replacement (e.g. pg 870, col. 1, Methods, In vitro differentiation), and thus is considered to be a pluripotent cell composition rendered “substantially free of immunogenic proteins”.
Biological Industries evidences that DMEM/F-12 culture medium is a protein-free culture medium.
Knockout serum replacement (KSR) medium is an art-recognized protein-free culture medium.
As discussed above in the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection, the phrases “for a period of time” and “substantially free of immunogenic proteins” renders the claim indefinite.
With respect to Claim 15, Takahashi et al taught a pluripotent cell formulation prepared by de-differentiating a population of autologous human fibroblasts prepared by the method.
Maherli et al taught a pluripotent cell formulation prepared by de-differentiating a population of autologous human fibroblasts prepared by the method.
As discussed above, the recitation of a process limitation in Claim 15, referring back to Claim 13, is not viewed as positively limiting the claimed product absent a showing that the process of making imparts a novel or unexpected property to the claimed product as it is assumed that equivalent products of pluripotent cells produced by de-differentiating autologous human fibroblasts are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed pluripotent cell product and referenced pluripotent cell product. The method in which the pluripotent cell product were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
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) 23 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Takahashi et al (2007; of record) in further view of Maherli et al (2008; of record), Shamis et al (2012; of record), and Kucharski et al (available online March 28, 2021; of record). as applied to Claims 13-15 and 22 above, and in further view of Mollamohammadi et al (2009; of record).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Takahashi et al nor Maherli et al teach wherein the thus-produced pluripotent cells are formulated to comprise a cryopreservation medium.
However, prior to the instantly claimed invention, and with respect to Claim(s) 23, Mollamohammadi et al is considered relevant prior art for having taught formulating induced pluripotent stem cells with a cryopreservation medium (e.g. Title, 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 instantly claimed invention, it would have been obvious to one of ordinary skill in the art to formulate a human pluripotent cell composition with a cryopreservation medium with a reasonable expectation of success because those of ordinary skill in the art had long-recognized and successfully reduced to practice the formulation of human pluripotent cell compositions comprising a cryopreservation medium, as the routineers previously recognized that an essential prerequisite for the future widespread application of human induced pluripotent cells is the development of efficient cryopreservation methods to facilitate their storage and transportation (e.g. Mollamohammadi et al, Abstract).
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).
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 Mollamohammadi et al do not remedy the deficiencies of Takahashi et al and iterates prior arguments of Takahashi et al and Mollamohammadi et al.
Applicant’s argument(s) has been fully considered, but is not persuasive. The Examiner’s response to Applicant's argument(s) regarding Takahashi et al and Mollamohammadi et al are discussed in prior Office Actions.
14. Claim(s) 24 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Takahashi et al (2007; of record) in further view of Maherli et al (2008; of record), Shamis et al (2012; of record), Kucharski et al (available online March 28, 2021; of record), and Mollamohammadi et al (2009; of record), as applied to Claims 13-15 and 22-23 above, and in further view of Maslowski et al (WO 08/027984; Applicant’s own work; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Mollamohammadi et al do not teach wherein the cryopreservation medium consists of IMDM, a cryopreservation medium, and 7.5% DMSO.
However, prior to the instantly claimed invention, and with respect to Claim(s) 24, Maslowski et al (Applicant’s own work) is considered relevant prior art for having disclosed a cryopreservation medium that consists of IMDM, ProFreezeTM, and 7.5% DMSO (e.g. pg 10).
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 instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first cryopreservation medium, as taught by Mollamohammadi et al, with a second cryopreservation medium consisting of IMDM, ProFreezeTM, and 7.5% DMSO, as disclosed by Applicant, 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.
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.
There is no objective evidence in the prior art, nor instant application, that a cryopreservation medium consisting of IMDM, ProFreezeTM, and 7.5% DMSO is material to patentability and/or provides some unexpected result. Rather, all that is required by the claimed invention is formulating a population of pluripotent cells with a cryopreservation medium, even more specifically, a cryopreservation medium consisting of IMDM, ProFreezeTM, and 7.5% DMSO, whereby those of ordinary skill in the art previously recognized and successfully reduced to practice the ability to formulate a population of pluripotent cells with a cryopreservation medium (e.g. Mollamohammadi et al), and a cryopreservation medium consisting of IMDM, ProFreezeTM, and 7.5% DMSO was a previously known cryopreservation medium formulary for human cells.
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).
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.
Conclusion
15. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638