DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed 13 June 2024 has been examined.
Claims 1, 3, 7, 8, 10–12, 17, 18, 20, 23, 28, 32, 34, 37, 44, 50, 56, 61, 69, 89–93, 97, 98, 102, 103, 107, 109, 110, and 114 are pending.
Claims 1, 3, 7, 8, 11, 12, 17, 18, 20, 23, 28, 32, 34, 37, 44, 50, 56, 61, 69, 89, 91, 92, 97, 102, 107, 109, and 114 are amended.
Claims 2, 4–6, 9, 13–16, 19, 21, 22, 24–27, 29–31, 33, 35, 36, 38–43, 45–49, 51–55, 57–60, 62–68, 70–88, 94–96, 99–101, 104–106, 108, 111–113, and 115 are canceled.
Benefit of Earlier Filing Date
The instant application was filed 20 November 2023; is a national stage application of PCT/US2022/031081, filed 26 May 2022, and claims the benefit of an earlier filing date of U.S. Prov. Pat. App. Serial No. 63/193,898, filed 27 May 2021. Applicant’s claim is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 August 2024 is acknowledged and has been considered.
Objections to the Specification
The abstract is objected to because it recites phrases that can be implied (“The present embodiments are directed to”).
Appropriate correction is required. Examiner recommends deleting the implied phrase and capitalizing the succeeding word (method): Methods of using a crystalline form . . .
For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Claim Objections
(i) Claims 1, 23, 90–92, 97, 102, 107, and 109 are objected to for improperly capitalizing certain words.
Trademarks may not be improperly used in claims. (MPEP § 2173.05(u)). In this case, the capitalizations appear to be a typographical error rather than a reference to a trademark because, e.g., terms like bitopertin and afamelanotide are common names for the compound in branded drugs. The capitalization of a common name is not necessary or proper.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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.
Claims 23, 28 and 90 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 23 recites, “healthy subject,” which is a relative term that renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Appropriate correction is required.
(ii) Claim 28 recites, “the patient.” Claim 28 depends from claim 1, which does not recite “a patient.” Thus, there is insufficient antecedent basis for using definite article “the” because there is no preceding introduction of the term in the claims with the article “a” or “an.”
Appropriate correction is required.
Examiner recommends amending “patient” to “subject.”
(iii) Claim 90 recites the trademark “(Scenesse®)” in connection with Afamelanotide.
A claim reciting a trademark to identify or describe a particular material or product does not comply with the requirements of 35 U.S.C. § 112(b). See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982); MPEP § 2173.05(u). The claim scope is uncertain because the trademark cannot be used properly to identify any particular material or product. A trademark is used to identify a source of goods—not the goods themselves. Thus, a trademark does not identify or describe the goods associated with the trademark.
Examiner recommends deleting the trademark and parentheses containing the trademark.
Claim Rejections - 35 U.S.C. § 102
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, 7, 11, 12, 17, 20, 28, 32, 34, 37, 44, 50, 56, 61, 69, and 114 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Halloy et al., Cell Chemical Biology (2021), 28, 1221–1234 [IDS] (“Halloy”) as evidenced by Bitopertin Product Information by Cayman Chemical, available at https://www.caymanchem.com/product/19896/bitopertin) (last visited 30 April 2026) (“Cayman”).
Halloy discloses a study of glycine transporters 1 (GlyT1) and 2 (GlyT2) inhibitors for the treatment of erythropoietic protoporphyria (EPP). (Halloy, Title, Abstract, p.1222).
Halloy investigated drugs like bitopertin that were known in the art to modulate enzymes and substrates in the HBS pathway. (Id., p.1224–1225). Bitopertin was determined to be one of the most potent at affecting HBS at early stages in the pathway. (Id., p.1225).
Halloy states: “EPP is a rare disease caused by the accumulation of the heme precursor PPIX in erythrocytes, inducing skin phototoxicity upon light exposure.” (Id., p.1229).
Halloy discloses a strategy for the treatment of EPP by lowering PPIX synthesis using GlyT1 and/or GlyT2 inhibitors. (Id., p.1229).
Halloy discloses the treatment of EPP cultures with bitopertin. (Id., FIG. 6, p.1230).
Halloy discloses compositions comprising bitopertin in DMSO [carrier] at concentrations of 50nM, 500nM, 1 mM, 5mM, 50 mM, and 150 mM. (Id., FIGs. 4, 6).
Halloy discloses the bitopertin was obtained from Cayman Chemical. (Id., p.e1).
Cayman states: “Bitopertin is supplied as a crystalline solid.” (Cayman, Lab. Procedures).
Claims 11, 12, 23, 28, 32, 34, 37, 44, 50, 56, 61, and 69 depend from claim 1 and further limit the subject matter thereof by reciting an intended result (e.g., “wherein the subject’s PPIX levels decrease . . .”). Courts have held that expressions of an intended result in a method claim are not given much patentable weight. (MPEP § 2111.04). In this case, the expressions of an intended result in claims 11, 12, 23, 28, 32, 34, 37, 44, 50, 56, 61, and 69 are not given much patentable weight because they are derived from a property of bitopertin as opposed to a structural feature of the bitopertin composition administered in the method. Because the treatment of EPP with bitopertin in Halloy would have been expected to be capable of the claimed intended results, the dependent claims are rejected as anticipated.
Claim Rejections - 35 U.S.C. § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 8, 10, 18, 89, and 90 are rejected under 35 U.S.C. § 103 as being unpatentable over Halloy as evidenced by Cayman in view of admissions in the instant specification (“Spec.”), Lecha et al., Orphanet J Rare Diseases (2009), 4(19), 10 pages (“Lecha”), Teramura et al., J. Derm. (2018), 45, 145–149 (“Teramura”), and Bugarski-Kirola et al., Biological Psychiatry (2017), 82, 8–16 (“Bugarski-Kirola”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
The discussion of Halloy above is hereby incorporated by reference and applicable to the rejected claims herewith.
Regarding claim 8, the instant specification states: “Enzymes that cause both EPP and XLPP are in the heme biosynthetic pathway. EPP and XLPP are nearly identical clinically.” (Spec., ¶3).
Regarding claim 10, Lecha states: “[EPP] usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters.” (Lecha, Abstract, p.1).
Regarding claim 18, Bugarski-Kirola states: “A graduate dose-dependent hemoglobin decrease was seen in patients receiving bitopertin.” (Bugarski-Kirola, p.11).
Regarding claims 89 and 90, Teramura states: “Photoprotection is the most essential and effective approach to avoid protoporphyrin IX activation and the resultant painful symptoms, such as skin burn and erythema. EPP patients must either wear a hat and clothing that covers their entire body when going out in the sun or remain indoors during the daylight hours.” (Teramura, p.145). Teramura states: “Sunscreens are effective in shielding the skin from ultraviolet (UV) light. However, the application of sunscreens does not completely prevent protoporphyrin IX activation because their protection efficacies for the visible light region are limited. (Id.).
Ascertaining the differences between the prior art and the claims at issue
Regarding claim 8, Halloy does not disclose XLPP.
Regarding claim 10, Halloy does not disclose the acute photosensitivity is due to sun exposure.
Regarding claim 18, Halloy does not state the PPIX is inhibited in a dose dependent manner. Bugarski-Kirola does not state the PPIX is inhibited in a dose-dependent manner.
Regarding claims 89 and 90, Halloy does not disclose administering a further agent, such as sunscreen.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Regarding claim 8, the instant application does not include evidence of nonobviousness related to the treatment of XLPP.
Regarding claim 10, the instant application does not include evidence of nonobviousness related to acute photosensitivity is due to sun exposure.
Regarding claim 18, the instant application does not include evidence of nonobviousness related to the dose dependent manner of PPIX inhibition.
Regarding claims 89 and 90, the instant application does not include evidence of nonobviousness related to administering a further agent.
The question of obviousness
Regarding claim 8, based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention based on the teachings of Halloy and the knowledge of one of skill in the art as evidenced by the specification, which acknowledges that EPP and XLPP present nearly identical at the clinic. Because of their identical presentation, one of ordinary skill in the art would have been motivated to administer bitopertin to a subject having EPP or XLPP based on Halloy; and there would have been a reasonable expectation of success because Halloy discloses the treatment of EPP cultures with bitopertin.
Regarding claim 10, based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention based on the teachings of Halloy and Lecha because Halloy discloses the treatment of EPP cultures with bitopertin and Lecha discloses the risks of sun exposure for those subjects having EPP. One of skill in the art would have been motivated to administer bitopertin to a subject with acute photosensitivity due to sun exposure because adverse reactions to sun exposure are a primary symptom of EPP. There would have been a reasonable expectation of success because Halloy discloses the treatment of EPP cultures with bitopertin.
Regarding claim 18, based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention to inhibit PPIX in a dose dependent manner based on the teachings of Halloy and Bugarski-Kirola because Halloy discloses the treatment of EPP cultures with bitopertin and Bugarski-Kirola discloses a dose-dependent hemoglobin decrease in patients receiving bitopertin. A dose-dependent decrease in PPIX would be expected based the corresponding dose-dependent decrease in hemoglobin. There would have been a reasonable expectation of success because the pharmacokinetic properties of bitopertin have been studied over several decades.
Regarding claims 89 and 90, based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention based on the teachings Halloy and Teramura because protecting a subject from symptoms caused by light exposure requires only common sense. Halloy discloses the treatment of EPP cultures with bitopertin and Teramura discloses that sunscreen has been tested on subjects with EPP. One of ordinary skill in the art would have been motivated to combine the administration of bitopertin with a commonly used topical composition to better protect the subject’s skin. There would have been a reasonable likelihood of success in the combination because the use of sunscreen is well-known in view of Teramura.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees.
A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046 (Fed. Cir. 1993); In re Longi, 759 F.2d 887 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937 (CCPA 1982); In re Vogel, 422 F.2d 438 (CCPA 1970); In re Thorington, 418 F.2d 528 (CCPA 1969).
Please note the following information regarding terminal disclaimers:
A timely filed terminal disclaimer in compliance with 37 CFR § 1.321(c) or § 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR § 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804(I)(B)(1). For a reply to a non-final Office action, see 37 CFR § 1.111(a). For a reply to final Office action, see 37 CFR § 1.113(c). A request for reconsideration while not provided for in 37 CFR § 1.113(c) may be filed after final for consideration. See MPEP § 706.07(e) and § 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, aor PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 7, 8, 10–12, 17, 18, 20, 23, 28, 32, 34, 37, 44, 50, 56, 61, 69, 89, 90, and 114 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1–23 of U.S. Pat. No. 11,813,257 (reference claims) as evidenced by Cayman.
But for claim 1 reciting “solid form” of bitopertin, several if not all of the rejected claims are identical to the reference claims. Although the claims at issue are not identical, they are not patentably distinct from each other because bitopertin is sold as a solid compound, as evidenced by Cayman. Thus, while the reference claims do not characterize the physical form of bitopertin, one of ordinary skill in the art would appreciate the claimed compound is a solid.
Allowable Subject Matter
Claims 91–93, 97, 98, 102, 103, 107, 109, and 110 are 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. None of the cited references disclose or suggest the specific solid forms as claimed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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