DETAILED ACTION
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 .
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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE on 11/25/25 and the amendment of claims has been entered.
Status of the Claims
Applicant’s election without traverse of IL-6 family protein, LIF and AMD was previously acknowledged.
In the reply filed 8/28/24, Applicants amended claims 1 and 11 were canceled.
In the reply filed 2/4/25, Applicants amended claims 1-3, 6-11, 13 and 16-20. Claims 4-5 and 14-15 were canceled.
In the RCE filed 11/25/25, Applicants amended claims 1 and 11 and canceled claims 2, 7, 10, 17 and 20.
Claims 1, 3, 6, 8-9, 11, 13, 16, 18-19 and 21 are pending.
Claims 1-3, 6-9, 11, 13, 16-19 and 21 read on the elected species and are under consideration.
Claim Rejections-Withdrawn
The rejection of claims 1-3, 6-9, 11, 13, 16-19 and 21 under 35 U.S.C. 103 as being unpatentable over Ash et al. (“Leukemia Inhibitory Factor (LIF) induces survival of Retinal Pigment Epithelium” ARVO Annual meeting abstract, April 2014,previously cited) in view of Xia et al. (“Effects of diabetic retinopathy on the barrier functions of the retinal pigment epithelium” Vision Research 139 (2017) 72-81) is withdrawn.
Response to Arguments
Applicant’s arguments with respect to claim(s) 11/25/25 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 112-NEW
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.
Claims 9 and 19 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. Claims 9 and 19 fail to further limit claims 1 and 11 because claims 1 and 11 were amended to limit the macromolecule to LIF. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. This is a NEW rejection necessitated by amendment of the claims.
Claim Rejections - 35 USC § 102-NEW
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 1-3, 6-9, 11, 13, 16-19 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al. (Chinese Medical Journal Jan. 2018, vol. 131, Issue 1; cited on IDS and provided by Applicant) as evidenced by Ueki et al. (Journal of Neurochemistry 2008; 105, pp. 784-796).
With respect to claims 1, 9, 11 and 19 and the limitation “wherein the condition is diabetic retinopathy”, Yang et al. teach diabetic retinopathy (DR) is an important cause of vision loss in working adults in developed countries (p. 1, 1st para.). Yang et al. teach that studies have suggested that changes in the functional molecules and viability of the neurons in the retina occur early after the onset of diabetes and precede the regression of the retinal vasculature (p. 2, top of 2nd col.). Yang et al. investigated the vascular changes and neuropathy in the retina of C57Bl/6J mice, a commonly used mouse strain. Yang et al. explored whether LIF prevents experimental diabetes-induced retinal injury in the early stages (p. 2, top of 2nd col.). Yang et al. teach diabetes was induced in C57BL/6 mice by i.p. injections of STZ. Diabetes was induced and the animal models were randomly separated into groups: diabetic group, diabetic +LIF and normal control group (non-diabetic)(Methods p. 2). LIF was injected intravitreally initiated 8 weeks after the diabetic model was successfully established (p. 2, bottom of 2nd col.). Yang et al. teach reduced RGCs and thinner INL in the diabetic mice compared with the normal control group. Vascular changes after diabetes induction, such as disorganized, dense distribution of capillaries and dilated capillaries within the retinal (p. 5, 2nd col.). Yang et al. teach the number of RGCs was significantly increased and capillary distribution became typical after the intravitreal injection of LIF (bottom of p. 5 and cont. to top of p. 6). Yang et al. states that LIF may be part of a retinal defense mechanism to increase the survival of ocular cells and improve the vascular changes that accompany diabetes. Yang et al. concludes that the study provides evidence that treatment with LIF preserved the integrity of the vasculature and prevented retinal injury in the early stages of DR and is a possible therapeutic strategy against DR (p. 6, last para.).
With respect “an effective amount”, the instant specification does not define or limit an effective amount. Yang et al. teach an amount sufficient to increase RGCs and preserve vascular integrity, meeting the limitation.
With respect to the limitation “wherein the macromolecule is the only active ingredient”, Yang et al. teach the only active ingredient is LIF.
With respect to “a subject”, the instant specification defines the subject to include humans and animals [PGPBUB0043 instant specification].
With respect to the limitation “a method for promoting angiogenesis in endothelial cells of a subject having a condition characterized by inadequate vascularization in the eye of a subject” and “wherein administration increases retinal microvessel density and does not induce vascular leakage” (claim 1), “wherein administration increases proliferation of choroidal endothelial cells” (claim 3) and “wherein the effective amount does not induce edema” (claim 8), “a method for inducing blood vessel formation in the eye of a subject”, “wherein the administration of the pharmaceutical composition increases angiogenesis in endothelial cells of the retina or choroid of the subject, increases retina microvessel density and does not induce vascular leakage” (claim 11), “wherein administration increases proliferation of choroidal endothelial cells” (claim 13), “wherein the effective amount does not induce edema” (claim 18), the method from Yang et al. would inherently have all of the activities and properties of the method of claim 1. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” In other words, Yang et al. teach administering the same composition (LIF) to the same patient population (a subject with diabetic retinopathy), therefore the same compound administered to the same patient population would inherently have the same properties. Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Importantly, MPEP 2112 states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer” and “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.
With respect to claims 6 and 16, LIF was injected intravitreally initiated 8 weeks after the diabetic model was successfully established (p. 2, bottom of 2nd col.).
With respect to claim 21, Yang et al. teach that LIF was injected intravitreally as described in Ueki (reference 25 of Yang et al.). Ueki et al. teach LIF in PBS for intravitreal injection (top of p. 785). Please note that MPEP 2131.01 states: that an extra reference or evidence can be used to show an inherent characteristic of the thing taught by the primary reference. In the instant case, the Ueki reference is relied upon only to establish LIF comprises a pharmaceutically acceptable carrier (PBS).
Response to Amendment
The Declaration under 37 CFR 1.132 filed 11/25/25 is insufficient to overcome the rejection of claims as set forth in the last Office action. The Declaration filed by Dr. Schwartz is not sufficient to overcome the new 102 rejection of record. Yang et al. teaches treatment of DR with LIF and anticipates the instant claims. Therefore, administering the same compound (LIF) to the same patient population (subjects with DR) would have the same properties such as increasing retinal microvessel density and not inducing vascular leakage.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/Examiner, Art Unit 1654