DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed and Arguments/Remarks, filed 22 June 2026, have been entered. Claims 1-16 are currently pending. Claims 1, 6, 9, and 14 are independent claims. Applicant’s election with traverse of the invention of Group I, drawn to a method of treatment of damaged liver tissue, is acknowledged.
Applicant’s traversal argues that:
if the search and examination of an entire application can be made without serious burden, the Examiner must examine it on the merits, even though it arguably may include claims to distinct or independent inventions, that it would not place an undue burden on the Examiner to search the subject matter of all the claims, Groups I-III together, and that a search directed to one Group would likely yield results applicable to other groups;
Restriction Requirements are optional in all cases and Applicant should not be required to incur the additional costs associated with the filing of multiple divisional applications in order to obtain protection for the claimed subject matter;
that Tarunina fails to disclose the specific polarization conditions or marker expression profiles recited in the present claims; specifically, Tarunina does not disclose macrophages polarized to pro-inflammatory M1 in presence of LPS+IFN-y so as to express elevated CD80, TNF-a and IL- 6, or macrophages polarized to anti-inflammatory M2 in presence of IL-4+IL-13 so as to express elevated CD206, CCL17, and CCL22; furthermore, Tarunina does not disclose or suggest the use of iPSC-derived polarized macrophages for treatment of damaged liver tissue, such as liver fibrosis; accordingly, the technical feature of macrophages derived from human induced pluripotent stem cells (iPSCs), wherein the macrophages are polarized to a pro-inflammatory M1 phenotype and/or an anti-inflammatory M2 phenotype, for use in the treatment of damaged liver tissue constitutes, a special technical feature that makes a contribution over the prior art.
However, this is not agreed.
Regarding Applicant’s argument 1), Applicant alleges that there would be no burden on the examiner in examining all of the claims at once, relying on M.P.E.P. §802.02. Chapter 800, however, is limited to a discussion of the subject of restriction and double patenting under Title 35 of the United States Code and Title 37 of the Code of Federal Regulations as it relates to national applications filed under 35 U.S.C. 111(a). The discussion of unity of invention under the Patent Cooperation Treaty Articles and Rules as it is applied as an International Searching Authority, International Preliminary Examining Authority, and in applications entering the National Stage under 35 U.S.C. 371 as a Designated or Elected Office in the U.S. Patent and Trademark Office is covered in M.P.E.P. §1850 and is dictated by PCT Rules 13.1 and 13.2. See M.P.E.P. §801. Burden is not a consideration in a finding of lack of inventive unity; rather, according to M.P.E.P. §1850, the only consideration is whether the inventions share a special technical feature.
Regarding Applicant’s argument 2), arguments that the Restriction Requirement is optional and that Applicant should not have to incur costs as a result of a Restriction Requirement is not an argument against the merits of the Restriction Requirement itself and does not distinctly and specifically point out a supposed error in the Restriction Requirement (see MPEP § 818.01(a)).
Regarding Applicant’s argument 3), Applicant argues that because Tarunina does not teach every limitation of the dependent claims, that the shared technical feature is a special technical feature and a unity of invention exists among the Groups I-III. However, the additional limitations which Applicant asserts are not taught by Tarunina are not recited in any of independent claims 1, 6, 9, nor 14, and therefore are not shared technical features. As discussed in the Restriction Requirement, the shared technical feature is merely a composition comprising a plurality of macrophages derived from hiPSCs, wherein the macrophages are polarized to a pro-inflammatory M1 phenotype and/or an anti-inflammatory M2 phenotype. As discussed in the Restriction Requirement, the shared technical feature is taught by Tarunina [0124, Figure 5C], and as such is not a special technical feature.
Therefore, the requirement is still deemed proper is therefore made FINAL.
Claims 6 and 9-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-5 and 7-8 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2022/037306, filed 15 July 2022, which claims priority to U.S. Provisional Application No. 63/224,318, filed 21 July 2021.
Thus, the earliest possible priority for the instant application is 21 July 2021.
Information Disclosure Statement
The information disclosure statement filed 18 January 2024 has been considered by the Examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The use of the terms “mTeSR” in [0089], “GlutaMAX” in [0089], “RNeasy” in [0093], “iScript” in [0093], “CFX384 Touch Real-Time PCR Detection System” in [0093], which are a trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that the specification has not been inspected sufficiently to identify all instances of trade names and/or marks used in commerce. It is Applicant’s responsibility to ensure complete compliance.
Additionally, the Brief Description of the Drawings for Figure 4 recites a panel “D”, but the Drawings Figure D does not have any label of “D”, and for Figure 10 describes panels “9A”, “9B”, and “9C” instead of “10A”, “10B”, and “10C”. Appropriate correction is required.
35 CFR 1.75
Applicant is advised that should claims 4 and 5 be found allowable, claims 7 and 8 will be objected to under 37 CFR 1.75 as being substantial duplicates thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Objections
Claims 5 and 8 are objected to because of the following informalities: claims 5 and 8 each recite “CCLI 7”, which appears to be a typographical error for “CCL17”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 3-5 and 7-8 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.
The term “reduces” in claim 3 is a relative term which renders the claim indefinite. The term “reduces ” 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. Although the specification uses the term “reduces” [see 0009 and 0027], the specification does not provide a limiting definition of the term which would indicate relative to what the fibrogenic gene expression and liver disease associated histological markers are reduced. As such, it is unclear whether the claim in meant to encompass a reduction relative to a starting condition, a control condition, or some other condition. Therefore, the metes and bounds of the claim cannot be determined.
The term “elevated” in claims 4-5 and 7-8 is a relative term which render the claims indefinite. The terms “elevated” is not defined by the claims, 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. Although the specification uses the term “elevated” [see 0010, 0011], the specification does not provide a limiting definition of the term which would indicate relative to what the expression is elevated. As such, it is unclear whether the claim in meant to encompass an elevation relative to a starting condition, a control condition, a different cell type or polarization state, or some other condition. Therefore, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Forbes [US20190240256A1, published 08 August 2019], as evidenced by Munn et al. [2021, PLOS One, 16(4), e0250107, 1-26, published 22 April 2021, IDS].
Forbes teaches a method of treatment of damaged liver tissue, comprising administering to a subject in need thereof an effective amount of a composition comprising a plurality of macrophages derived from human induced pluripotent stem cells (iPSCs) [0010, 0017, 0064, 0109, claim 22], wherein the macrophages are polarized to an anti-inflammatory M2 (i.e., alternatively activated) phenotype and express CD206 [0009, 0046, 0048, 0065, 0169, claim 12].
Forbes also teaches polarization of iPSC-derived macrophages to an inflammatory M1 (classically activated) phenotype and administration of macrophages polarized to an M1 phenotype which express CD80 [0023, 0065, Figure 26].
Forbes also teaches wherein the subject has liver fibrosis [0050, 0055].
Forbes further teaches wherein the administration reduces fibrogenic gene expression (i.e., reduces α-SMA expression) [0088, 0125, 0138, Figure 18] and liver disease associated histological markers (i.e., decreased Sirius Red staining and reduction in necrotic area) [0094, 0097, 0125, Figure 3, 7].
Forbes does not explicitly teach wherein the M1 macrophages express elevated TNF-α and IL-6 nor wherein the M2 macrophages express CCL17 and CCL22.
However, gene expression profiles are inherent properties of cells. Munn teaches that human iPSC-derived macrophages polarized to M1 express high levels of CD80, TNF-α, and IL-6 [pg 11 ¶ 2- pg 12 ¶ 1, pg 15 ¶ 3, Figure 6, S5]. Munn also teaches that human iPSC-derived macrophages polarized to M2 express high levels of CD206, CCL17, and CCL22 [pg 12 ¶ 1-2, pg 15 ¶ 3, Figure 6, S6, S8]. Therefore, Munn teaches that human iPSC-derived macrophages inherently express elevated CD80, TNF-α, and IL-6 when polarized to an M1 phenotype and express elevated CD206, CCL17, and CCL22 when polarized to an M2 phenotype. As such, the human iPSC-derived macrophages, as disclosed by Forbes, are considered to inherently express elevated CD80, TNF-α, and IL-6 when polarized to an M1 phenotype and express elevated CD206, CCL17, and CCL22 when polarized to an M2 phenotype, absent evidence to the contrary.
“When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Accordingly, by teaching all of the limitations of claims 1-5 and 7-8, Forbes anticipates the instant invention as claimed.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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