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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 03 March 2026 has been entered.
Response to Amendment
Applicant’s amendment to the claims and specification has been received and entered. Claims 1, 7, 13 and 14 have been amended, claims 19-26 have been added and claims 2-6, 8-12 and 15-18 have been canceled. Claims 1, 7, 13-14 and 19-26 are currently pending and under consideration in the instant Office action.
Newly submitted claim 26 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the original claims were directed to use of a peptide consisting of SEQ ID NO:1, a medicament comprising a peptide consisting of SEQ ID NO:1 and a method of treatment which administers a peptide consisting of SEQ ID NO:1. Claim 26 is directed to a method which administers manuka honey or a medicament comprising MRJP3 (major royal jelly protein 3). Neither manuka honey nor MRJP3 encompass the invention which was presented and examined in the original claims filed 01 November 2021. The peptide consisting of SEQ ID NO:1 is not found in manuka honey nor is it found in MRJP3. Furthermore, the peptide consisting of SEQ ID NO:1 has physiological effects distinct from either manuka honey or MRJP3 as evidenced by Figures 2 and 10. The methods are distinct as they administer materially distinct compounds which are structurally and functionally distinct and do not overlap in scope.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 26 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Specification
The disclosure is objected to because of the following informalities: the last sentence on page 11 of the specification does not end in a period.
Appropriate correction is required.
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The title makes no mention of the agent which is being administered. Additionally, the claims are not directed to methods of reducing risk of any disease condition.
The abstract of the disclosure is objected to because it does not relate to the invention of the instant application. The invention does not “use” “a peptide or fragment comprising SEQ ID NO:1” nor is the invention directed to a method of “reducing the risk” of any disease/disorder. Furthermore, the invention is not a mixture of manuka honey and royal jelly. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 7, 13, 14 and 19-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The instant claims are directed to a “method of treating cardiovascular disease, diabetes, or adiposity” by administering to a subject or “the subject taking” a peptide consisting of SEQ ID NO: 1 to “bring about in the subject one or more of:” reduced blood concentration of triglycerides, LDL, sdLDL, glucose, or insulin or reduced HbA1c or increased insulin sensitivity. However, the instant claims are not enabled for treating any disease/condition as broadly claimed.
First, the instant claims do not require the subject being treated actually have any of the conditions for which the peptide consisting of SEQ ID NO:1 is being administered. One cannot treat a disease/condition if the subject to whom the compound is being given does not have the disease/condition.
Next, the instant claims are not enabled for treating the recited conditions as broadly recited because the physiological effects of administration of the peptide consisting of SEQ ID NO:1 would not suggest that the recited conditions would be “treated”. The instant specification does not provide any examples of a subject with any of the recited conditions or administration of the peptide consisting of SEQ ID NO:1 in which the outcome was treatment of the recited conditions. While it is not required that the specification reduce to practice the claimed invention, the evidence provided in the instant specification does not support the breadth of the current claims. The first trial (beginning at page 6 of the specification) administered the peptide consisting of SEQ ID NO:1 to wild-type male mice (control) and Leprdb mice (defective leptin receptor, therefore, leptin resistant). The results of the administration are found in Figures 1-7. As can be seen, the administration of the peptide consisting of SEQ ID NO:1 had no effect on growth rate, body mass, plasma insulin, plasma glucose, HOMA-IR, total cholesterol, or heart rate in the control mice. Therefore, administration of the peptide consisting of SEQ ID NO:1 would not be expected to result in a reduction of triglycerides, sdLDL, insulin or glucose and an increase in insulin sensitivity as none of these parameters were achieved by administration of the peptide consisting of SEQ ID NO:1 to control or normal mice. Therefore, the claims are not enabled for methods of treating any of the recited conditions in subjects who are not suffering from any of the recited conditions of the claims.
The claims are directed to treating cardiovascular disease by administration of the peptide consisting of SEQ ID NO:1. However the instant specification does not provide any evidence of record that such administration would result in the treatment of cardiovascular disease and additionally, the specification contains evidence that cardiovascular disease may be adversely affected by such administration. Cardiovascular disease is not a singular condition, but rather it encompasses a number of different conditions such as coronary artery disease, stroke, heart failure and arrhythmia. A number of different things can cause cardiovascular disease or be risk factors for cardiovascular disease such as atherosclerosis, high blood pressure, high cholesterol, diabetes, obesity and genetic predisposition. While the instant specification does demonstrate that administration of the peptide consisting of SEQ ID NO:1 had the ability to reduce LDL and mean arterial blood pressure in control mice, administration also increased heart mass, which is not considered beneficial for treating cardiovascular disease and in most instances is an indication of cardiovascular disease. Therefore, one of ordinary skill in the art would not conclude that administration of the peptide consisting of SEQ ID NO:1 would result in the treatment of cardiovascular disease, absent evidence to the contrary.
The claims are directed to treating diabetes by administration of the peptide consisting of SEQ ID NO:1. First, the claims do not distinguish between the different types of diabetes and the examples in the specification would only pertain to type II diabetes which presents with insulin resistance and/or reduced insulin secretion. Type I diabetes is a condition in which the body’s immune system attacks and destroys the insulin-producing beta cells in the pancreas. The data in the instant specification do not support the treatment of type I diabetes because administration of the peptide consisting of SEQ ID NO:1 does not increase plasma insulin.
With regard to type II diabetes, administration of the peptide consisting of SEQ ID NO:1 decreased plasma insulin in the Leprdb mice. One of ordinary skill in the art would not consider this physiological effect of administration to necessarily be a treatment for type II diabetes. In the early to middle stages of type II diabetes, plasma insulin levels are elevated because the body has become resistant to insulin. A reduction in insulin levels would not be considered therapeutic because it would further impair the subject’s ability to regulate glucose levels. In the later stages of type II diabetes, the body produces less insulin and subjects frequently require injections of insulin in order to properly regulate blood glucose. Additionally, Figure 2 also shows that administration of the peptide consisting of SEQ ID NO:1 in the Leprdb mice increased plasma glucose at the same time that the administration decreased plasma insulin. One of ordinary skill in the art would not consider such physiological effects to be compatible with a method of treating type II diabetes, which typically presents with elevated glucose levels. While Figure 3B demonstrates that administration of the peptide consisting of SEQ ID NO:1 improved insulin sensitivity in the Leprdb mice, this effect is not sufficient to conclude that administration would result in an effective treatment for type II diabetes in light of the other negative effects on parameters of type II diabetes. The specification provides no examples which would model diabetes in general or type II diabetes, specifically and one of ordinary skill in the art would not conclude that the physiological effects achieved by the administration of the peptide consisting of SEQ ID NO:1 would be effective for treating diabetes as broadly claimed, absent evidence to the contrary.
The claims are directed to treating adiposity by the administration of the peptide consisting of SEQ ID NO:1. Adiposity is the condition of having excessive body fat accumulation and causes include such things as genetics, caloric imbalance, inactivity, poor diet, high stress, poor sleep, hormone imbalances, hypothyroidism as well as medications. The instant specification provides data to show that administration of the peptide consisting of SEQ ID NO:1 had no effect on total cholesterol or HDL in control mice but did decrease LDL in both control and Leprdb mice as well as reducing cholesterol in Leprdb mice. However, this data does not support a method of treating adiposity as none of these parameters directly correlate to overall body fat such that modulation of any one parameter is predictive of a reduction in overall body fat. The Leprdb mouse does not appear to be a recognized animal model for treatment of adiposity and one of ordinary skill in the art would not readily conclude that a reduction in LDL would effectively treat adiposity, absent evidence to the contrary.
The specification also discloses a second trial in which manuka honey was ingested by control mice or Leprdb mice. The specification states a “second trial was run to test whether oral consumption of manuka honey as a source of the 125mer peptide would give the same results as administration by injection”. However, oral administration of manuka honey does not equate to administration of the peptide consisting of SEQ ID NO:1. There is no evidence in the instant specification that manuka honey, when orally administered, results in a peptide consisting of SEQ ID NO:1. While the peptide consisting of SEQ ID NO:1 is fragment of the larger protein comprising the amino acid sequence of SEQ ID NO:2 (SEQ ID NO:1 is contained within SEQ ID NO:2; amino acid positions 253-377 of SEQ ID NO:2), there is no evidence of record which would indicate that the protein of SEQ ID NO:2 is proteolytically processed such that the peptide consisting of SEQ ID NO:1 would be produced and absorbed in the gut following ingestion of manuka honey. Manuka honey is a product which contains numerous proteins and other compounds which have a vast array of biological properties ranging from anti-oxidant, anti-inflammatory, anti-bacterial, anti-viral, anti-biotic and wound healing to immune-stimulatory properties (see Patel et al. Nat. Prod. Bioprospect. 2013, 3, 121-128). The peptide consisting of SEQ ID NO:1 of the instant application is part of a larger protein which is found in royal jelly (MRJP3) and which is not a protein that is found in manuka honey. Royal jelly is a secretion from the glands of worker honey bees and is not a component of honey. Therefore, the results from the second trial (beginning at page 9 of the specification) do not relate to or encompass administration of the peptide consisting of SEQ ID NO:1 because this peptide would not be expected to be found in manuka honey which was administered in this trial.
Regarding oral administration of the peptide consisting of SEQ ID NO:1, the instant application fails to enable such methods. The peptide consisting of the amino acid sequence of SEQ ID NO:1 does not appear to be a naturally occurring peptide. Muresan et al. (cited by Applicant in the instant specification) teach that royal jelly protein 3 is proteolytically digested in the human GI tract and that functional domains of full-length MRJPs may be destroyed before they can enter the bloodstream (see page 4164, column 2, last sentence of the first paragraph). Muresan et al. teach that proteins are proteolytically digested in the GI tract and therefore, one of ordinary skill in the art would reasonably conclude that the peptide consisting of SEQ ID NO:1 would be subject to proteolytic degradation if orally administered. The instant claims lack essential method steps/components which would be necessary for oral administration of the peptide consisting of SEQ ID NO:1 such that the peptide reached the GI tract without degradation such that it could be absorbed and elicit any physiological effects that it may possess. The instant specification fails to teach any means for administering the peptide consisting of SEQ ID NO:1 and relies upon administration by “oral consumption of manuka honey as a source of the 125mer peptide”. However, consumption of manuka honey would not result in oral administration of the peptide consisting of SEQ ID NO:1 because (1) the peptide is a fragment of MRJP3 which is not necessarily found in manuka honey and (2) there is no evidence of record that MRJP3 is proteolytically broken down in the gut to the 125mer peptide consisting of SEQ ID NO:1. Therefore, the claims are not enabled for oral administration of the peptide consisting of SEQ ID NO:1 as broadly claimed.
Based on the observations made above and the disclosure of the instant specification, the instant application is enabled for a method of reducing LDL and increasing insulin sensitivity in a subject in need thereof by subcutaneous administration of the peptide consisting of SEQ ID NO:1. However, the full scope of claim 1 and dependent claims 7, 13, 14 and 19-25 is not enabled for the reasons provided above.
Response to Arguments
Applicant argues that the claims are enabled for oral administration at page 2 of the response. Applicant asserts:
The specification provides sufficient information for the notional person with ordinary skill in the art to make or use the concept described in this claim. If the skilled person can prepare a truncated peptide for an injection, the same skill could be applied to preparing a peptide for oral ingestion. Moreover, the 125mer peptide merely needs to be administered to a subject and can be sourced from e.g. manuka honey (as per [0097]). It is also noted that protein and peptide drugs (PPDs) have been administered orally since well before the application's priority date. Please refer to Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C₁₀) (Pharmaceutics 2019, 11, 78; Twarog et al.; published 13 February 2019)( attached). This article mentions that, at that time, about 4% of PPDs were administered orally. In other words, it is possible to deliver a peptide orally - and it would not be beyond the ability of the notional skilled person. Applicant submits that a person having ordinary skill in the art would be able to replicate the concept of each of the amended claims. That is to say, none of the claims require extraordinary skill or information beyond the common general knowledge and the specification.
Applicant’s arguments have been fully considered as well as Applicant’s evidence which was submitted (Twarog et al.), however, neither are found persuasive. The instant specification fails to teach or suggest use of intestinal permeation enhancers and the specification only discloses oral administration by way of ingestion of manuka honey. The claims are not enabled as they are currently drafted for the reasons outlined above. The claims are lacking a critical method step and/or component which would provide for the oral administration of the peptide consisting of SEQ ID NO:1 such that any physiological effects that may be exerted by the peptide consisting of SEQ ID NO:1 would be realized. There is no evidence of record that the peptide of SEQ ID NO:1 could be orally administered and result in any therapeutic effect being achieved by the administration.
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.
Claim 1 is 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.
Claim 1 recites “or the subject taking”. The metes and bounds of “taking” cannot be determined from the claim or how “taking” would distinguish over the claimed limitation of “administering”. Therefore, the claim is indefinite.
Citation of Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Saheera et al. Cell Transplantation. 29: 1-10, 2020.
Wang et al. Curr. Diabetes Rev. 10: 131-145, 2014.
Borgeson et al. Front. Cell. Dev. Biol. 10:1003118. doi: 10.3389/fcell.2022.1003118.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Z Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
