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 .
Objections
Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art to the instant claims is US2005/0226812A1, which teaches a 64 residue peptide, SEQ ID NO: 33, which aligns with instantly claimed SEQ ID NOs: 19, 20 and 7. However, there is no teaching or motivation to suggest limiting the peptide to 50 residues in length.
Although 1-7 and 9 are free of the art, they are drawn to a naturally occurring product, as will be discussed below. Claim 8 is not subject to 35 USC 101 because of the types of cargo listed in claim 8, which renders it markedly different from the naturally occurring product.
Claim Rejections 35 USC 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring composition without significantly more. The claim(s) recite(s) a naturally occurring protein fragment. This judicial exception is not integrated into a practical application because claims 1-7 and 9 are drawn only to the naturally occurring protein fragments, without additional elements, or any structural or functional differences recited. The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they only amount to a portion of a naturally occurring human CD300lf protein where peptide bonds were broken. The analysis is as follows:
1: Is the claim drawn to a composition of matter? Yes
2A: Is the claim drawn to a product of nature? Yes —SEQ ID NOs: 19, 20 and 7 are drawn to a portion of the naturally occurring protein, human CD300lf, having the following alignment:
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250
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Virgin et al. (US2018/0252712; Alignment from Search Report for SEQ ID NO: 7, which also reads on the genus of SEQ ID NO: 19 and 20). Virgin et al. teach that SEQ ID NO: 56 is a human derived CD300lf protein [0069] and Sino Biological further teaches that human CD300lf proteins are known to be naturally occurring in the human spleen, leukocytes and lungs and act as inhibitory receptors for myeloid cells and mast cells, positively regulate the phagocytosis of apoptotic cells via phosphatidylserine recognition and recognize and binds PS as a ligand, which is expressed on the surface of apoptotic cells (see p. 3-4, Sino Biological; https://www.sinobiological.com/resource/cd300f-cd300lf, cited here as evidence of CD300lf sources).
2B: Does the claim recite additional elements that amount to significantly more than the judicial exception? No — the only difference is that the peptide is taken from the full length 108 residue peptide, and the breaking of chemical bonds does not render the peptide markedly different from the naturally occurring product.
The Court in Myriad found that naturally occurring fragments of DNA were not significantly different from the natural product where the only modification is the breaking of a chemical bond (Ass ’n for Molecular Pathology v. Myriad Genetics , Inc., 133 S. Ct. 2107, 2116- 17, 106 USPQ2d 1972, 1978-79, 2013). With regard to the chemical process required to isolate a particular segment of DNA, the court stated: “...extensive effort alone is insufficient to satisfy §101’s demands. Myriad’s claims are not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together. The claims are not expressed in terms of chemical composition, nor do they rely on the chemical changes resulting from the isolation of a particular DNA section.” (id. at 2).
Unlike Myriad, the claims are drawn to a naturally occurring peptide that is not, and not to naturally occurring DNA, but the same logic applies, even if the 10-50 residue peptide is not the entire length of the natural protein. Because the only difference between the natural product and the instantly claimed peptide is that it is isolated from the natural source, human CD300lf, claims 1-5 are drawn to a judicial exception and not patent eligible under 35 USC 101.
As to claims 6 and 7, these are drawn to SEQ ID NO: 19 attached to cargo, but cargo may simply be additional peptides and proteins (as discussed in claim 7), which read on SEQ ID NO: 19 attached to an additional 40 residues of the naturally occurring CD300lf protein. Similarly, the only difference is the breaking of chemical bonds within the 50 residue maximum length, which meets the limitations of claim 9, as the additional 40 residues would be covalently attached SEQ ID NO: 19 via a peptide bond, but the shortened composition would still be a fragment of the CD300lf protein.
Claim Rejections 35 USC 112(A)
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 17-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for transporting therapeutic agents into colon and breast cancer stem cells, does not reasonably provide enablement for treating and preventing all types of neoplastic disease, immune disease, cardiovascular disease, inflammatory disease, neurological disease or lysosomal disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Note that because of the extremely broad scope of claim 17 and the focus on neoplastic diseases of claims 18 and 19, cancer prevention and treatment overall, as well as CPP predictability will be the focus of the foregoing rejection.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (1) The breadth of the claims; (2) The nature of the invention; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The level of predictability in the art; (6) The amount of direction provided by the inventor; (7) The existence of working examples; and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) (reversing the PTO's determination that claims directed to methods for detection of hepatitis B surface antigens did not satisfy the enablement requirement). In Wands, the court noted that there was no disagreement as to the facts, but merely a disagreement as to the interpretation of the data and the conclusion to be made from the facts. In re Wands, 858 F.2d at 736-40, 8 USPQ2d at 1403-07. The Court held that the specification was enabling with respect to the claims at issue and found that "there was considerable direction and guidance" in the specification; there was "a high level of skill in the art at the time the application was filed;" and "all of the methods needed to practice the invention were well known." 858 F.2d at 740, 8 USPQ2d at 1406. After considering all the factors related to the enablement issue, the court concluded that "it would not require undue experimentation to obtain antibodies needed to practice the claimed invention." Id., 8 USPQ2d at 1407.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561,27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. leva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorerlnc., 49 USPQ2d 1370.
For legal background, there are four cases that provide particular relevance to the question of enablement of standardizing a method of treating cancers broadly or generally:
In In re Buting, 57 CCPA 111, 418 F.2d 540, 163 USPQ 689, the claim was drawn to “The method of treating a malignant condition selected from the group consisting of leukemias, sarcomas, adenocarcinomas, lymphosarcomas, melanomas, myelomas, and ascitic tumors” using a small genus of compounds. The Court decided that human testing “limited to one compound and two types of cancer” was not “commensurate with the broad scope of utility asserted and claimed”.
In Ex parte Jovanovics, 211 USPQ 907 the claims were drawn to “the treatment of certain specified cancers in humans” by the use of a genus of exactly two compounds, the N-formyl or N-desmethyl derivative of leurosine. Applicants submitted “affidavits, publications and data” for one of the compounds, and a dependent claim drawn to the use of that species was allowed. For the other, no data was presented, applicants said only that the other derivative would be expected to be less effective; claims to the genus were refused.
In Ex parte Busse, et al., 1 USPQ2d 1908, claims were drawn to “A therapeutic method for reducing metastasis and neoplastic growth in a mammal” using a single species. The decision notes that such utility “is no longer considered to be “incredible”, but that “the utility in question is sufficiently unusual to justify the examiner's requirement for substantiating evidence. Note also that there is also a dependent claim 5, which specified “wherein metastasis and neoplastic growth is adenocarcinoma, squamous cell carcinoma, melanoma, cell small lung or glioma.” The decision notes that “even within the specific group recited in claim 5 some of the individual terms used actually encompass a relatively broad class of specific types of cancer, which specific types are known to respond quite differently to various modes of therapy.”
In Ex parte Stevens, 16 USPQ2d 1379 a claim to “A method for therapeutic or prophylactic treatment of cancer in mammalian hosts” was refused because there was
“no actual evidence of the effectiveness of the claimed composition and process in achieving that utility.”
Regarding In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), it is necessary to consider the following factors when determining whether undue experimentation is required: (1) The breadth of the claims; (2) The nature of the invention; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The level of predictability in the art; (6) The amount of direction provided by the inventor; (7) The existence of working examples; and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) The nature of the invention and (5) The breadth of the claims:
Claims 17 is drawn to a method of treating or preventing any neoplastic, neurological, inflammatory, lysosomal, and infectious disease with the claimed cell penetrating peptide. This is very broad in that it is drawn to any type of cargo being successfully able to treat any of these countless diseases and condition categories. A focus on the enablement of treating and preventing cancer and CPP delivery in general will be used in this rejection.
Claims 18 and 19 are drawn to neoplastic treatments and prevention via cell targeting and delivery of cargo. Regarding neoplastic treatments, there are many different types of these diseases (i.e., cancer), but all share one hallmark characteristic: unchecked growth that progresses toward limitless expansion (National Institute of Cancer- understanding and related topics, accessed 11/29/25 at URL: https://www.cancer.gov/about-cancer/understanding/what-is-cancer). Cancers are highly heterogeneous at both the molecular and clinical level, and cancer is the name given to a collection of diseases, not just one particular disease. As such, the patient classes, etiologies and treatments can vary widely (id. at p. 2). Therefore, even treatment or prevention of cancer generally is very broad, in that the compounds used must be known to be effective in treating a very wide variety of this collection of diseases.
(2) The state of the prior art:
Regarding cell penetrating peptide (CPP) mediated delivery of peptides and proteins Kristensen (Int. J. Mol. Sci. 2016, Vol. 17, No. 185) teaches that cell penetration may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo (abstract). This reference further teaches that both approaches have their pros and cons, but they are dependent on the physicochemical properties of the CPP and its cargo, as well as the route of administration, the specific barrier and the target cell (abstract). Kristensen also teaches that along with the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are often needed to prolong the CPP half-life (abstract). The mechanisms by which CPPs translocate cell membranes involve both endocytosis and direct translocation, and the fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP makes the delivery of cargo via CPPs unpredictable and complicates the design and conduction of conclusive mechanistic studies (abstract).
As such, the breadth of the claims being enabled for any cancer prevention and treatment or for penetrating of any type of cell with any type of cargo is recognized as unpredictable by the prior art.
(3) The relative skill of those in the art:
Regarding cancer and specifically effective treatment, the prior art teaches that there never has been a compound capable of treating cancers generally. “The cancer therapy art remains highly unpredictable, and no example exists for efficacy of a single product against tumors generally.” (<http://www.uspto.gov/web/offices/pac/dapp/1pecba.htm#7>ENABLEMENT DECISION TREE, Example F, situation 1). A similar statement appears at In re Application of Hozumi et al., 226 USPQ 353: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
Accordingly, there is substantive “reason for one skilled in the art to question the objective truth of the statement of utility or its scope” (In re Langer, 183 USPQ 288, 297).
Accordingly, there is substantive “reason for one skilled in the art to question the objective truth of the statement of utility or its scope” (In re Langer, 183 USPQ 288, 297).
Similarly, In re Novak, 134 USPQ 335, 337-338, says “unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them.” There is no such evidence in this case. Likewise, In re Cortright, 49 USPQ2d 1464, states: “Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient” does what the specification surmises that it does. That is exactly the case here. Even if applicants’ assertion that cancer in general could be treated with these compounds were plausible— which it is not —, that would not suffice, as was stated in Rasmusson v. SmithKIine Beecham Corp., 75 USPQ2d 1297, 1301: “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success.”
The relative skill of those in the art is high because of the complex nature of cancer treatment, and the inefficacy of treatments in treating all types of cancer in all patients.
(4) The predictability or unpredictability of the art:
With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] .. . anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”. More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Compounding what is known about cancer treatment unpredictability, together with CPP unpredictability makes effective treatments for the scope of diseases claimed highly unpredictable.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
Applicant’s specification only provides examples of SEQ ID NO: 7 internalizing cargo into HCT116 (colon carcinoma cells) and MDA-MB-231 (breast cancer cells) in examples 3 and 4, where example 4 shows a preference for internalizing the cargo into cancer stem cells in MDA-MB-231 cells vs. non-cancer stem cells. No additional clear guidance as to other categories of cells that would be penetrable with the claimed peptides has been provided, and there are no examples of treatment and/or prevention guidance as to what types of cargo this would be limited to, as the specification defines cargo as “all the substances that can be transported inside the cell via conjugation with a cell-penetrating peptide, for example, drugs, cosmetics, or active ingredients” (p. 16, para. 3).
(8) The quantity of experimentation necessary:
Because it is uncertain to predict what new cancer treatment and prevention will be effective for various types of cancer, and especially in view of factors 1-7, the quantity of experimentation needed is expected to be undue by the precedential court standard for determining the enable of treating or preventing cancer.
MPEP 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).”
In this case, that conclusion is supported by both legal and scientific standards.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654