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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11-25-2025 has been entered.
Applicant's arguments and amendments to the claims filed on 11-25-2025 have been received and entered. Claim 16-17 have been amended. Claims 8, 10-12, 14, 24-28, 30-31 have been canceled. Claims 1-7, 9, 13, 15-23, 29 are pending.
Election/Restrictions
Applicant’s election without traverse of Group II (Claims 16-17, 21-23, 25, and 29) in the reply filed on 04-10-2024 is acknowledged.
Claims 1-7, 9, 13, 15, 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04-10-2024.
Claims 16-17, 21-23 and 29 are under consideration.
Priority
This application is a 371 of PCT/IB2019/001130 filed on 10/18/2019 that claims priority from US provisional application No 62/747,797 filed on 10/19/2018.
Maintained in modified form and New -Claim Rejections - 35 USC § 103 - necessitated by amendments
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.
Claims 16-17, 21-23 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Gammelsaeter et al. (Pub. No.: US 2015/0313950 Al, Pub. Date: Nov. 5, 2015) (Applicant own work) as evidenced by Novobrantseva et al (Pub. No .: US 2021/0189342 A1, provisional application No. 62/692,463, filed on Jun 29, 2018.) and as evidenced by Hamill et al (Pub. No .: US 2021/0260010 A1, provisional application No. 62/687,724 , filed on Jun 20 , 2018) and in view of and/or as evidenced by Hu et al (Arch Dermatol. 2009;145(4):437-439) and in view of and/or as evidenced by Franklin et al (Int Wound J 2015; 12:548–554, doi: 10.1111/iwj.12159).
Regarding to claim 16-17, Gammelsaeter et al teaches a method of improving wound healing comprising applying a heat-treated fish egg cellular extract prepared as described above or a cream, gel, emulsion, ointment, spray, powder or lotion comprising the heat-treated fish egg cellular extract to a subject having a wound ([0007], page 1). The invention provides a topical formulation comprising a fish egg cellular extract ([0010], page 2), and the dose administered to an animal, particularly a human ([0205], page 21). In some embodiments, the fish egg cellular extract is a salmonid egg cellular extract. In some embodiments, the salmonid is selected from the group consisting of salmon and trout. In some embodiments, the fish egg cellular extract comprises about 100 to 380 mg/ml protein in an aqueous solution; about 0.1 to 10 mg/ml RNA; about 0.1 to 5 mg/ml DNA ([0011], page 2).
Gammelsaeter et al teaches that the composition of the present invention also finds use in wound healing. A wound is a break in the skin (the outer layer of skin is called the epidermis) ([0226], page 23). Furthermore, Gammelsaeter et al teach treating Necrobiosis lipoidica diabeticorum which is a plaque like, depressed, atrophic yellow lesion typically found in patients with diabetes. It has a strong association with diabetes and actually may be a clinical prodrome of the onset of the disease systemically. It rarely is found in locations other than the lower extremities and seldom is found in the absence of diabetes. The lesion tends to progress from a red plaque like area to one with atrophy that occasionally may ulcerate ([0240], page 25). Gammelsaeter et al also teach the compositions can also comprise modulators of diabetes (e.g., glyburide or chlorpropamide) ([0175], page 18).
Additionally, Hu et al teach “treatment of refractory ulcerative necrobiosis lipoidica diabeticorum” (title) and Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous inflammatory skin disease associated with diabetes mellitus, and skin lesions usually develop on the lower extremities and can progress toward ulceration and scarring (Abstract). Hu et al reported a case of a patient with a history of type 1 diabetes mellitus who presented with lower extremity ulcers developing from erythematous papules and plaques that were histopathologically consistent with NLD (Page 437, left column, last para.). Hu et al teach the patient experienced a fulminant expansion and ulceration of the lesions, with the ulcers extending over her shin and calf (Page 438, left column, and Figure 2) and Seventy-five percent of patients with NLD have or will develop diabetes mellitus (type 1 more often than type 2) (Page 438, right column, 1st para.)
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Also, Franklin et al teach “Ulcerated necrobiosis lipoidica as a rare cause for chronic leg ulcers: case report series of ten patients” (title), and “data of altogether ten patients (nine women and one man) with ulcerated necrobiosis lipoidica were collected. Of these, 70% of the patients had diabetes mellitus of which 30% had type I diabetes and 40% had type II diabetes” (Abstract), and necrobiosis lipoidica diabeticorum is associated with diabetes mellitus, and the extent of this association has been often discussed and varies between 22% and 65% (Page 549, left column, 1st para).
Thus, a person of ordinary skill in the art would be motivated to use Gammelsaeter et al ‘s teaching of a salmonid egg cellular extract to administer to an animal, particularly a human having Necrobiosis lipoidica diabeticorum for improving wound healing of diabetic foot ulcer as taught by Hu et al and/or Franklin et al.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to apply and modify the Gammelsaeter et al ‘s teaching to use a salmonid egg cellular extract to treat a diabetic foot ulcer as taught by Hu et al and/or Franklin et al instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because (i) Gammelsaeter et al provide explicit advantage of stimulating fibroblast migration, stimulating elastin production, reducing expression of inflammatory factors and upregulating specific genes, thereby preventing skin cell aging processes and repairing skin damage (abstract). Gammelsaeter et al also stated that the compositions of the present invention enhance or improve wound healing in a subject ([0275], page 28); (ii) Hu et al teach that first line therapies treatment of NLD include topical and intralesional corticosteroids. Smoking cessation and diabetic control may also be effective because reports have documented the beneficial effects of thiazolidinediones in NLD (Page 438, right column, 2nd para), and “Infliximab should be considered in the treatment of refractory, ulcerative NLD. Its anti–tumor necrosis factor activity may underlie its efficacy in targeting this granulomatous process” (Abstract); (iii) Franklin et al stated that “Our results show a strong correlation between ulcerating necrobiosis lipoidica and aspects of metabolic syndrome. All patients in our study showed one or more cardiovascular risk factors. Without dispute there is a strong correlation for necrobiosis lipoidica particularly with diabetes mellitus” (page 552, right column, last para.), and “ulcerating necrobiosis lipoidica can be seen as part of a generalised inflammatory reaction similar to the inflammatory reaction already known in the pathophysiology of rheumatoid diseases or psoriasis” (Abstract). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Gammelsaeter et al were successful in producing and applying fish egg extracts for wound healing with detailed instructions and working examples, and Hu et al and Franklin et al provided guidance for treating ulcerated necrobiosis lipoidica diabeticorum.
Regarding to claim 29, Gammelsaeter et al teaches in some embodiments, the cellular extract is provided in a cream, gel, emulsion, ointment, spray, powder or lotion ([0004], page 1).
Regarding to claims 21, 22 and 23, Although Gammelsaeter et al do not specifically teach cell mediators such as IL-1 RA, IL-6, IL-10 and VEGF is increased, and IL-12 , TNF-α, MCP-1, and IL-8 is decreased in macrophages (for claim 21-22) and Gammelsaeter et al do not specifically teach AMAC-1 (known as CCL18 ) is increased (for claim 23), Gammelsaeter et al do teach the same salmon egg cellular extract composition with the same amount of components as the claimed invention for chronic wound treatment as described above, and Gammelsaeter et al teaches an extract component or components that stimulate macrophages ([0208], page 21). Thus, since the method is rendered obvious, it is expected that human subject with similar wound treatment with Gammelsaeter et al ’s same salmon egg cellular extract composition as claimed invention would have the same macrophages gene expression profile as the claimed invention.
As evidenced by Novobrantseva et al who teach using egg yolk compositions and methods for modulating monocyte and macrophage inflammatory phenotypes: Macrophages having an increased inflammatory phenotype exhibit one or more of the following after contact with the agent or agents: increased expression and/or secretion of IL-10, and decreased secretion of at least one cytokine selected from the group consisting of TNF- α, IL-12 ([0010], page 2). Exemplary surface-active agents include egg yolk ([0727], page 248). Since Novobrantseva et al teach the use of surface-active agents such as egg yolk to modulate macrophage to increase expression of IL-10 and decrease TNF- α, IL-12, a person of ordinary skill in the art would recognize that egg components would be able to increase expression of IL-10 and decrease TNF- α, IL-12 in macrophage during healing of chronic wound (for claim 21-22).
As evidenced by Hamill et al who teach using egg white compositions for reducing or treating diabetic inflammation: The composition is capable of increasing, or increases, anti-inflammatory chemokine secretion by at least 50% , 60% ,70% , 80% , 90% , 95% , or more as detected using an assay of CCL18 in primary human monocyte -derived macrophages ([0126], page 6). Composition comprises non-amino acid entity protein components (e.g., claim 8 page 55) that include one or more of egg white protein ([0088], page 4-5). Thus, a person of ordinary skill in the art would recognize that egg white protein components are capable of stimulating macrophages to increase secretion of anti-inflammatory chemokine such as CCL18 (AMAC-1) (for claim 23).
As per MPEP 2112 (II), inherent feature need not be recognized at the relevant time: 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) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999).
Response to Arguments
Applicant's arguments filed on 11-25-2025 have been fully considered but they are not persuasive.
Applicants disagree that NLD is a distinct condition as compared to diabetic foot ulcers and the two diseases have distinct etiologies/mechanisms. Specifically, NLD is a chronic inflammatory skin disorder that causes yellow-brown, atrophic plaques, usually on the shins. Furthermore, NLD does not present as an ulcer and is a skin change caused by collagen degeneration. In contrast, diabetic foot ulcers are an open sore on the foot that develops due to a combination of peripheral neuropathy, poor circulation, and repetitive pressure or trauma. The diabetic foot ulcers often cause a breakdown of both the skin and deeper tissue. Because NLD and diabetic foot ulcers are distinct diseases, there is no basis for a person of ordinary skill in the art to apply a treatment for NLD to diabetic foot ulcers and there would be no reasonable expectation of success (Remarks, page 6).
Response to Arguments:
It appears that Applicant is arguing that the cited references do not expressly suggest the claimed invention. However, it is well established in case law that a reference must be considered not only for what it expressly teaches, but also for what it fairly suggests. In re Burkel, 201 USPQ 67 (CCPA 1979). Furthermore, in the determination of obviousness, the state of the art as well as the level of skill of those in the art are important factors to be considered. The teaching of the cited references must be viewed in light of these factors. The is cited Gammelsaeter et al to show that methods and compositions of salmon egg cellular extract can be used enhance or improve wound healing in a subject including necrobiosis lipoidica diabeticorum. Hu et al reported a case of a patient with a history of type 1 diabetes mellitus who presented with lower extremity ulcers developing from erythematous papules and plaques that were histopathologically consistent with NLD (Page 437, left column, last para.). Hu et al teach that the patient experienced a fulminant expansion and ulceration of the lesions, with the ulcers extending over her shin and calf including her foot (Page 438, left column, and Figure 2) and Seventy-five percent of patients with NLD have or will develop diabetes mellitus (type 1 more often than type 2) (Page 438, right column, 1st para.). Thus, a person of ordinary skill in the art would be motivated to use Gammelsaeter et al ‘s teaching of a salmonid egg cellular extract to administer to an animal, particularly a human having Necrobiosis lipoidica diabeticorum for improving wound healing of diabetic foot ulcer as taught by Hu et al and/or Franklin et al, with reasonable expectation of success.
Conclusion
No claim is allowed.
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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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