DETAILED ACTION
Claims 1-12 are pending and being examined on the merits in this office 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 .
Priority
The filing receipt dated 01/14/2025 provides the following:
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Following a review of the file wrapper, it does not appear that a certified copy of the foreign priority document has been received.
Drawings
The drawings are objected to for the following reasons. Figures 4 and 5 need a unit of measurement on the y-axis. Compare with Figs 2A-C and 3A-C which have a unit of measurement. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Examiner Comment
Examiner recommends that claim 1 be amended to recite “amino acid sequence of
Claim Rejections - 35 USC § 112
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.
Claims 4-6 are 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 4 recites the limitations "the splenocytes", “the expression”, and “the secretion”. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the limitations "the keratinocytes" and “the expression”. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitations "the keratinocytes" and “the activity”. There is insufficient antecedent basis for this limitation in the claim.
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 7-11 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 full length SEQ ID NO:1 reducing inflammatory cytokines in vitro, does not reasonably provide enablement for treatment of prevention of an inflammatory 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 practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (5) The breadth of the claims:
The invention is drawn to a pharmaceutical composition for preventing or treating an inflammatory disease comprising the peptide of claim 1as an active ingredient. Claim 1 is drawn to a peptide comprising the amino acid sequence represented by SEQ ID NO: 1.
The specification states that the peptide has anti-inflammatory activity. The specification states at paras [0033]-[0035]:
[T]he term “peptide” refers to a linear molecule consisting of amino acid residues, and specifically, the peptide of the present invention may include the amino acid sequence represented by SEQ ID NO: 1.
The “peptide” may be variants or fragments of amino acids having different sequences due to deletion, insertion, substitution, or combinations of amino acid residues, to the extent that they do not affect its function. Amino acid exchanges that do not change the entire activity of the peptide are known in the art. In some cases, the peptide may be modified by phosphorylation, sulfation, acrylation, glycosylation, methylation, farnesylation, etc. Accordingly, the peptide of the present invention includes a peptide having an amino acid sequence substantially identical to the peptide containing the amino acid sequence of SEQ ID NO: 1, and a variant or active fragment thereof.
The substantially identical protein refers to an amino acid sequence having sequence homology of 75% or more, preferably 80% or more, for example, 85% or more, 90% or more, 95% or more, 98% or mom, or 99% or more with the amino acid sequence of SEQ ID NO: 1, but is not limited thereto, and as long as the protein has 75% or more of amino acid sequence homology and has the same activity, it is included in the scope of the present invention.
The specification states at paras [0052]-[0055]:
As used herein, the term “inflammatory disease” may be defined as a pathological symptom, which is caused by an inflammatory response characterized as a local or systemic biological defense response to autoimmunity or infection from external physical and chemical stimuli or external infectious agents (e.g., bacteria, fungi, viruses, various allergens, etc.). The inflammatory response involves a series of complex physiological reactions, such as activation of various inflammatory mediators and enzymes associated with immune cells (e.g., iNOS, COX-2, etc.), secretion of inflammatory mediators (e.g., secretion of TNF-α, IL-6, IL-8, IL-17, IL-1β, IFN-γ, etc.), infiltration of body fluids, cell migration, tissue destruction, etc., and may appear externally through symptoms, such as erythema, pain, edema, fever, and deterioration or loss of certain functions of the body.
Since the inflammatory disease may be acute, chronic, ulcerative, allergic, or necrotic disease, it includes all acute, chronic, ulcerative, allergic, or necrotic diseases as long as any disease is included as an inflammatory disease as described above.
Specifically, the inflammatory disease may be an inflammatory skin disease or inflammatory autoimmune disease.
The inflammatory skin disease may include atopic dermatitis, contact dermatitis, allergic skin disease, acne, and urticaria.
The term “treating” or “treatment” are not expressly defined in the specification. The specification states” As used herein, the term “prevention” refers to all actions that inhibit or delay the occurrence, spread, and recurrence of inflammation by the peptide of the present invention or a composition including the same” (para [0057]).
(2) The state of the prior art: the following reflects just a few disorders that falls within the claim scope of “inflammatory diseases”.
The Merck manual indicates that there are plethora of inflammatory disorders known, for example, Pelvic Inflammatory Disease, Temporomandibular Disorders, and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), to name just a few (see Merck manual, Inflammatory Disorders enclosed). Additionally, the Merck manual indicates that there are numerous numbers of types of dermatitis, for example, contact dermatitis, stasis dermatitis, perioral dermatitis, atopic dermatitis (Eczema) to name just a few (see Merck manual, Dermatitis enclosed- previously cited). Additionally, the Merck manual indicates that there are plethora of inflammations (see Merck manual, Inflammation enclosed- previously cited).
Inflammation of skin or mucosa can have an underlying genetic cause. Bowcock et al (Human Molecular Genetics 13: R43-R55 (2004)) teach that genetic skin disorders include, but are not limited to hyper-IgE syndrome (HIES), Wiskott–Aldrich syndrome, Familial eosinophilia (FE), Netherton’s disease, psoriasis and atopic dermatitis. See Bowcock et al generally.
With regard to Multiple Sclerosis, another inflammatory disease, although there have been substantial progress reported in the scientific literature about the multiple etiologies of multiple sclerosis, including genetic makeup and environmental factors, multiple sclerosis remains a “difficult disease for which solutions seem attainable yet remain elusive” (Compston et al., The Lancet 359:1221-1231 (2002) at p. 1221, para. 1 and p. 1224, para. 6 – p. 1225, para. 2). See also p. 1226-1228 discussing the various treatments of MS with β-interferons and synthetic amino acid polypeptides, corticosteroids, etc.
Rheumatoid arthritis (RA; accessed 10/24/2017 at URL merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders (pp. 1-26) is a chronic systemic autoimmune disease that primarily involves the joints (abstract). RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically, peripheral joints (e.g., wrists, metacarpophalangeal joints) are symmetrically inflamed, leading to progressive destruction of articular structures, usually accompanied by systemic symptoms. Id. Treatment of RA involves supportive measures (nutrition, rest, analgesics), drugs that modify disease progression (e.g., TNF-alpha antagonists, IL-1 receptor antagonists, IL-6 blockers, B-cell depleters, T-cell costimulatory molecules, and Janus kinase (JAK) inhibitors, and corticosteroids), and surgery (pp. 14-25).
Hypersensitivity and reactive skin disorders (Merck Manual, overview of hypersensitivity and reactive skin disorders, accessed 6/25/2023 at URL merckmanuals.com/home/skin-disorders/hypersensitivity-and-reactive-skin-disorders/overview) teach that the immune system plays a vital role in maintaining the health of all the tissues of the body. Some hypersensitivity reactions are called allergies, especially when they occur after exposure to substances that are usually harmless to most people. Hypersensitivity reactions can involve the skin and cause disorders such as the following: drug rashes, erythema multiforme, erythema nodosum, granuloma annulare, keratosis pilaris, Stevens Johnson syndrome, and toxic epidermal necrolysis. Treatment depends on the cause of the disease/disorder.
Psoriasis and scaling diseases (Merck Manual, introduction to psoriasis and scaling diseases, accessed 6/25/2023 at URL merckmanuals.com/home/skin-disorders/psoriasis-and-scaling-disorders) teach that psoriasis, parapsoriasis, pityriasis rosea, pityriasis rubra pilaris, lichen planus, and lichen sclerosus are different skin disorders that have been grouped together because the bumps, rashes, scales, and skin discoloration they cause have similar characteristics. That is, the rashes and bumps have well-defined borders, and the scales usually do not crust, crack, or weep with fluid.
The art recognizes that there are countless different types of inflammations and inflammatory diseases, but does not provide how to determine the individuals who are susceptible to these inflammatory.
(3) The relative skill of those in the art:
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(4) The predictability or unpredictability of the art:
Applicant’s activity is based on the determination of predicting those who are susceptible to ALL forms of inflammation/inflammatory diseases, across different species, and different organs and tissues. Since the activity is based on determining the patient population that is susceptible to disorders, conditions and diseases, the predictability in the art is low. This is due to the fact that the art has recognized that there are plethora of different inflammatory diseases, but does not provide how to determine the individuals who are susceptible to any inflammatory disease.
Applicant has not shown who will be susceptible to an inflammatory disease. There are too many variables between the patient populations [further complicated by genetic predispositions and prophylactic treatment- both of which are encompassed by the claim scope], thus, it clearly shows the unpredictability of the art.
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Furthermore, the claimed “inflammatory diseases” encompass different diseases with distinct etiologies and pathologies. Adding to the unpredictability is that many treatment options may show promise in animal models, but may fail to show therapeutic improvement in clinical trials. There is no absolute predictability, even in view of the high level of skill in the art.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
Synthesis Example 1 discloses preparation of a peptide comprising 100% identity to SVSVGMKPSPRP (SEQ ID NO:1). Experimental Example 1 discloses a reduction in the expression of inflammation-associated genes associated after creating an inflammatory environment with LPS in splenocytes. SEQ ID NO:1 also reduced the secretion of inflammatory cytokines TNF-α, IFN-γ, and IL-17. Experimental Example 2 discloses a reduction in the secretion of inflammatory cytokines TNF-α, IL-1β, and INFγ.
Experimental Example 3 discloses a reduction in the expression of inflammation-associated genes associated after creating an inflammatory environment in keratinocytes.
No examples of treatment or prevention of any inflammatory disease was reduced to practice. Disorders that fall within the instant claim scope also include genetic disorders. There is no guidance in the specification as to how to treat, much less prevent, the genetic disease.
The specification has not provided guidance as to the type of inflammatory diseases. There is no clear guidance as to the patient population, since not all people suffer from the same disorder, condition or disease, and the amount to treat ALL inflammatory diseases. The identity of the patient/subject is not clear. Thus, given the broadest reasonable claim interpretation, the claim scope encompass ALL species for treatment with the claimed peptide. Since the art recognizes that there are countless different inflammatory diseases, but does not provide how to determine the patients/subjects who are susceptible [much less treatment regimens/dosages/etc- to treat or prevent] to respective inflammatory diseases, more guidance is necessary.
(8) The quantity of experimentation necessary:
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).” That conclusion is clearly justified here.
In order to treat a disease, a dosage, the subject and treatment regimen must be identified. It cannot be forgotten that the instant claim scope encompasses prophylactic treatment, e.g., preventing. It is uncertain to predict the patient population who are susceptible for any inflammatory disease. Applicant have not provided the appropriate time frame at which the claimed peptide should be administered, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” to determine if the peptide would be effective in treating an adult, child, or an infant from all forms of inflammatory diseases.
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.
Claim(s) 1-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Peled et al (WO 03/072599- cited in IDS filed 2/25/2025).
Peled et al teach chemokine binding peptides, including SVSVGMKPSPRP (BKT-P130, Table 1, p. 28). The peptide has 100% identity with instant SEQ ID NO:1. Accordingly, the limitations of claim 1 are satisfied. Regarding claim 2, Peled et al teach that the peptides can be used to treat an inflammatory condition. The peptides are effective modulators of cell adhesion and cell migration which characterize inflammatory reaction [reads on anti-inflammatory activity] (pp. 6-7, 12, 23-24). It is further noted that MPEP § 2112.01 recites, "Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established." In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties. 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." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding claim 3, Pedel et al compositions comprising the peptides, e.g. at pp. 4, 6-7, Example 2. It is noted that the instant specification does not explicitly define “anti-inflammatory composition”. Thus, a composition comprising the chemokine binding peptide BKT-P130 (instant SEQ ID NO:1) is deemed to read on claim 1.
Regarding claims 4-6, MPEP § 2112.01 recites, "Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established." In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties. 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." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Although Pedel et al do not specifically teach the limitations of splenocyte cytokine expression or keratinocyte iNOS or COX-2 activity as recited in claims 4-6,
the reference does teach that the peptides have anti-inflammatory activity. The claimed composition appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2ⁿᵈ 1992 (PTO Bd. Pat. App. & Int. 1989). Accordingly, the limitations of claims 4-6 are satisfied.
Regarding claim 7, Pedel et al teach pharmaceutical compositions comprising the chemokine binding peptide BKT-P130 (instant SEQ ID NO:1), e.g. at pp. 4, 6-7, Example 2. Regarding claims 8-9, Pedel teaches that the peptides can be topically administered and used to treat an inflammatory skin disease, e.g. allergy (pp, 7-8, 12, examples 2-3). Regarding claims 10-11, Pedel teaches that the peptides can be used to treat an inflammatory autoimmune disease, e.g. multiple sclerosis or rheumatoid arthritis (pp, 7-8, 12, examples 2-3).
Alternatively, claims 8-11 can be deemed to recite an intended use of theclaimed composition, e.g., treating or preventing the recited inflammatory diseases. A recitation of an intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding claim 12, the instant specification does not explicitly define a “cosmetic composition”. However, Pedel et al teach that the peptides can be administered topically to the skin, and used to treat disorders, e.g. psoriasis, vitiligo, or alopecia (e.g., at pp 7-8, 13, Examples 2-3). Accordingly, the composition comprising the chemokine binding peptides BKT-P130 (instant SEQ ID NO:1) for topical administration satisfies limitations of claim 12.
Conclusion
No claims are allowed.
Claims 1-12 are pending and are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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