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
The election without traverse filed November 4, 2025, is acknowledged and has been entered. Applicant has elected Group III and the anti-inflammatory agent, IL-10.
The amendment filed November 4, 2025, is acknowledged and has been entered. Claims 1-16, 18 and 32 have been canceled. Claims 40-53 have been newly added.
Claims 21-22 and 40-53 are pending. Claims 40-41 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected species of invention, there being no allowable generic or linking claim.
Claims 21-22 and 42-53 are pending and are under examination.
Information Disclosure Statement
The information disclosure statements and third-part submission have been considered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless -
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Regarding claim 45: For the purposes of applying prior art because it is unclear how a liver specific promoter or cirrhosis specific promoter differs from a promoter in general and livers contain macrophages and other cells where a liver-specific promoter may function as a promoter, macrophage promoters are being included as liver-specific promoters, absent a showing otherwise. Notably, if liver specific promoters were intended to be limited to only promoters that function in hepatocytes, the nucleic acids with a liver specific promoter in an immune cell would not express exogenous IL-10.
Claims 21-22, 42-45, 47 and 51-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han et al (FASEB J., 24:2869-2880, 2010).
With respect to claims 21, 22, 42, 43 and 47, Han et al disclose methods of delivering modified immune macrophages comprising a nucleic acid that express exogenous IL-10 to subjects to treat or prevent vascular fibrosis or inflammation (IL-10 overexpression in macrophages suppresses atherosclerosis) (see abstract and pages 2973, 2876-2878 and Figures). With respect to claim 44, Han et al disclose that the IL-10 is secreted from the macrophage (see page 2870). With respect to claim 45, Han et al disclose the nucleic acid comprises the macrophage promoter of CD68 which is a “liver specific promoter” as claimed, because macrophages are 2% of the liver.
With respect to claims 51 and 52, Han et al disclose the macrophages are derived from hematopoietic stem cells from bone marrow cells (see abstract and page 2879). With respect to claim 53, Han et al disclose the macrophages can be M-CSF derived (2870-2871).
Therefore, Han al is deemed to anticipate the instant claims absent a showing otherwise.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 21-22, 42-46 and 51-53 are rejected under 35 U.S.C. 103 as being unpatentable over Han et al (FASEB J., 24:2869-2880, 2010) and Hume et al, (J. of Leuk. Bio., 89:525-538, 2011).
With respect to claims 21, 22, 42, 43 and 47, Han et al disclose methods of delivering modified immune macrophages comprising a nucleic acid that express exogenous IL-10 to subjects to treat or prevent vascular fibrosis or inflammation (IL-10 overexpression in macrophages suppresses atherosclerosis) (see abstract and pages 2973, 2876-2878 and Figures). With respect to claim 44, Han et al disclose that the IL-10 is secreted from the macrophage (see page 2870). With respect to claim 45, Han et al disclose the nucleic acid comprises the macrophage promoter of CD68 which is being interpreted as encompassed by the term “liver specific promoter” because macrophages are 2% of the liver and it is unclear what the term “liver specific promoter” encompasses as set forth above and absent a showing otherwise.
With respect to claims 51 and 52, Han et al disclose the macrophages are derived from hematopoietic stem cells from bone marrow cells (see abstract and page 2879). With respect to claim 53, Han et al disclose the macrophages can be M-CSF derived (2870-2871).
Han et al does not disclose using a CX3CR1 promoter.
Hume et al disclose relevant to claims 46, that CX3CR1 is another promoter that drives expression in macrophages along with CD68 and others (see Table 2). Hume et al disclose relevant to claim 53, that M-CSF and GM-CSF are growth factors involved in macrophage differentiation (see page 525).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine these references and incorporate the CX3CR1 promoter and M-CSF and GM-CSF of Hume into the methods of Han because the CX3CR1 promoter is another art recognized macrophage promoter that could be used to express IL-10 in macrophages that were derived from M-CSF and GM-CSF differentiation.
Therefore, using the CX3CR1 promoter and M-CSF and GM-CSF, absent a showing otherwise, would be seen as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Furthermore, one of skill in the art would have expected success in using the CX3CR1 promoter and M-CSF and GM-CSF as the prior art of Hume et al disclose how to use the CX3CR1 promoter to express exogenous transgenes and M-CSF and GM-CSF in differentiation.
Accordingly, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
Claims 21-22, 42-45 and 48-53 are rejected under 35 U.S.C. 103 as being unpatentable over Han et al (FASEB J., 24:2869-2880, 2010) and Hotter Corripio et al (US 2018/0087031 A1).
With respect to claims 21, 22, 42, 43 and 47, Han et al disclose methods of delivering modified immune macrophages comprising a nucleic acid that express exogenous IL-10 to subjects to treat or prevent vascular fibrosis or inflammation (IL-10 overexpression in macrophages suppresses atherosclerosis) (see abstract and pages 2973, 2876-2878 and Figures). With respect to claim 44, Han et al disclose that the IL-10 is secreted from the macrophage (see page 2870). With respect to claim 45, Han et al disclose the nucleic acid comprises the macrophage promoter of CD68 which is being interpreted as encompassed by the term “liver specific promoter” because macrophages are 2% of the liver and it is unclear what the term “liver specific promoter” encompasses as set forth above and absent a showing otherwise.
With respect to claims 51 and 52, Han et al disclose the macrophages are derived from hematopoietic stem cells from bone marrow cells (see abstract and page 2879). With respect to claim 53, Han et al disclose the macrophages can be M-CSF derived (2870-2871).
Han et al does not disclose using a M2 macrophages.
Hotter Corripio et al disclose relevant to claims 48-50, inducing polarized M2 macrophages and that these M2 macrophages overexpress IL-10 important from the amelioration of inflammation (see abstract and page 1). While these M2 macrophages are not further characterized as in claim 50, it is noted that M2 macrophages are either M2A, M2B, M2C, or M2D macrophages and claim 50 recites all 4 types, so the M2 macrophages of Hotter Corripio et al are at least one or more of the subtypes of claim 50.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine these references and incorporate M2 macrophages of Hotter Corripio et al into the methods of Han so that the M2 macrophages express exogenous IL-10 along with endogenous IL-10 because M2 macrophages are involved in the resolution of inflammation which is involved in the atherosclerosis of Han. Notably, the macrophages of Han may in fact be M2 macrophages or comprise M2 macrophages because these macrophages overexpress IL-10, but since these macrophages were not characterized as M2 macrophages it is noted that it would be obvious to select M2 (anti-inflammatory macrophages) that additionally express exogenous IL-10 to ensure that anti-inflammatory macrophages were being delivered to the subject. Notably, Hotter Corripio et al also disclose that “Macrophages are therefore a population of immune cells that orchestrate a diverse array of functions including inflammation, tissue repair, and immune responses. This functional diversity is achieved by the remarkable heterogeneity of macrophages, which have the capacity to dramatically change their phenotype as a result of differentiated plasticity as well as local environmental cues” (see ¶4), so it is apparent that one would not want to administer macrophages involved in “increasing inflammation” (see ¶31) and one would be motivated to select M2 macrophages that are anti-inflammatory macrophages.
Therefore, M2 macrophages, absent a showing otherwise, would be seen as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Furthermore, one of skill in the art would have expected success in using M2 macrophages in such methods as the prior art of Han et al disclose how to transfect macrophages and Hotter Corripio et al disclose how to obtain M2 macrophages.
Accordingly, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
Conclusion
No claims are allowed.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
February 5, 2026