DETAILED ACTIONS
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 .
Priority
This is a national stage entry of 35 U.S.C. 371 of PCT/CN2021/094932 (filed on 05/20/2021) and claims benefit to foreign application CHINA 202110231913.4 (filed on 03/02/2021).
Election/Restrictions
Applicants’ election of Group I, drawn to a method of the recited conditions, on 05/19/2026 is acknowledged. Claims 1,2,4, and 16-20 read on the elected invention.
Applicants fully complied with the election of species requirement by electing “treating heart disease associated with cardiac injury” as “the method”, “TBX1 encoding sequence” as the “active ingredient”, and “anti-CD8 antibody” as the “additional active ingredient”.
Upon reconsideration, the election of species requirement is withdrawn in its entirety. The claims of Group I have been examined for their full scope.
Claims Status
Claims 1-2,4-7,16-20 are pending.
Claims 5-7 are withdrawn per invention election filed on 05/19/2026.
Claims 1-2, 4, 16-20 have been examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 recites …wherein “promoting the transformation of M1-type macrophages to M2-type macrophages” includes promoting the transformation of M1-type macrophages (promoting inflammatory response) into M2-type macrophages (promoting tissue repair) in myocardial tissue. As claim 4 is dependent on claim 1, which does not specify where the M1 to M2 macrophage transition is occurring and is given the broadest reasonable interpretation of the M1 to M2 transition occurring in every tissue, as the administration of the active ingredient is to a subject not a specific tissue or cell, claim 1 already includes the transition occurring in myocardial tissue.
35 U.S.C.§ 112(d) requires that a claim further limit a previous claim. It would be remedial to rewrite claim 4 to recite, “… wherein the promoting of the transformation of M1-type macrophages to M2-type macrophages occurs in myocardial tissue.”
For compact prosecution, the claim is being interpreted as “,…wherein the promoting of the transformation of M1-type macrophages to M2-type macrophages occurs in myocardial tissue.”
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1,2,4,16-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vitelli et al (Genesis, 2009) evidenced by Martucciello et al ( FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 2020; as cited in the IDS filed on 08/31/2023) and Houssari et al ( Arteriosclerosis thrombosis, and vascular biology, 2020; as cited in IDS filed on 04/28/2025).
Vitelli et al teaches of a novel mouse transgenic line COET, which expresses Tbx1 upon Cre mediated recombination (See, Abstract).
Regarding claims 1, 2, 4, 16-19, Vitelli et al teaches that the COET transgenic mouse line was generated by injecting into mouse blastocyst a COET construct comprising full length Tbx1 cDNA that was cloned into loxP-flanked neomycin resist cassette, a poly-A tail in a pBALNLXGFP backbone vector (See, p4 paragraph 4-5, Figure 1 for construct). The vector is then electroporated into embryonic stem cells, the cells selected and positive clones were injected into mouse blastocysts (See, p4 paragraph 5). This reads on, a method of… which comprises administering an active ingredient to a subject in need thereof, wherein the active ingredient comprises: a promoting agent thereof (of TBX1) of claim 1, as the subject in this instance is the mouse blastocyst and it would be in need therefore to activate proliferation of cardiac lymphatic endothelial cells, and the vector that is injected promotes the expression of Tbx1.
This also reads on, wherein the active ingredient is administered to the subject in a form of pharmaceutical formulation of claim 18.
This also reads on, wherein the pharmaceutical formulation comprise (a)…a cell containing the expression vector, and (b) excipient, of claim 19 as the injection contains cells handling or injection medium would be a part of the microinjection.
While Vitelli is silent on the effects of the methods, Martucciello et al teaches that Tbx1 has a role in cardiac lymphangiogenesis and interacts with Vegfr3 in the formation of cardiac lymphatics (See, p 15078 col 1 paragraph 2). Houssari et al teaches that treatment with soluble VEGFR3 limits T-cell recruitment to cardiac infarct after myocardial infraction, which results in delayed scar remodeling and reduced myocardial dysfunction (See, p1723 and p1728-1729 col 1). Due to the direct relationship between TBX1 and VEGFR3 taught by Martucciello et al and the teaching of Houssari et al that VEGFR3 treats myocardial infraction through T-cell recruitment, shows that the overexpression of Tbx1 inherently would result in repairing cardiac injury and activating proliferation of cardiac lymphatic endothelial cells.
This reads on, a method of : (i) activating proliferation of cardiac lymphatic endothelial cells and (iv) repairing cardiac injury and the other effects (ii, iii, and v) as they are inherent of claim 1. Under the principles of inherency, when a reference discloses all claimed steps, the effect will necessarily be achieved, even if not explicitly recognized by the reference. See MPEP 2112.02.
This also reads on, wherein the heart diseases associated with cardiac injury…myocardial infarction of claim 2.
This reads on, wherein the “promoting the transformation of M1-type macrophage to M2-type macrophages” occurs in myocardial tissue of claim 4, as this is an inherent effect of the method.
This reads on, wherein the subject reveals reduced scar tissue area in heart after administration of claim 16, as this would be an inherent effect of the method.
This reads on, wherein the subject exhibits improved cardiac ejection fraction and a corresponding decrease in left ventricular end-diastolic volume after administration of claim 17, as this would be an inherent effect of the method.
Therefore, claims 1,2,4,16-19 are anticipated by Vitelli et al and evidenced by Martucciello et al and Houssari et al.
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Vitelli et al (Genesis, 2009) as applied to claims 1,2,4, and 16-19 above, and further in view of Ilatovskaya et al (Amer. Journal of physiology. Heart and circulatory physiology, 2019).
The teachings of Vitelli et al are set forth above.
Regarding claim 20, following the discussion above, Vitelli et al does not teach administering the pharmaceutical formulation of tbx1 with an additional active ingredient of anti-CD8 antibodies.
Ilatovskaya et al teaches CD8+ T-cells regulate post-myocardial infarction (MI) would healing process. Ilatovskaya et al also teaches that mice without functional CD8+ T-cells had improved cardiac physiology and less mortality post MI compared to wild-type (See, Abstract).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the pharmaceutical formulation to further comprise anti-CD8 antibodies. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification to pharmaceutical formulation to include anti-CD8 antibodies to improve cardiac physiology, as anti-CD8 antibodies would block CD8+ T cells by binding to the CD8 protein on its surface. One would have had a reasonable expectation of success taught by Ilatovskaya et al.
Therefore, claim 20 is rendered obvious by Vitelli et al in view of Ilatovskaya et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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/CAROLINE M LARA/
Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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