DARPA-BAA-12-31.pdf

Broad Agency Announcement Butyrylcholinesterase Expression in Plants

DSO

DARPA-BAA-12-31

FEBRUARY 16, 2012

I. FUNDING OPPORTUNITY DESCRIPTION

II. AWARD INFORMATION

III. ELIGIBILITY INFORMATION

A. ELIGIBLE APPLICANTS

B. PROCUREMENT INTEGRITY, STANDARDS OF CONDUCT, ETHICAL CONSIDERATIONS,

AND ORGANIZATIONAL CONFLICTS OF INTEREST

C. COST SHARING/MATCHING

D. OTHER ELIGIBILITY CRITERIA

IV. APPLICATION AND SUBMISSION INFORMATION

A. ADDRESS TO REQUEST APPLICATION PACKAGE

B. CONTENT AND FORM OF APPLICATION SUBMISSION

1. Security and Proprietary Issues

2. Abstract Submission Information

3. Proposal Submission Information

4. Abstract Format

5. Full Proposal Format

a. Volume I, Technical and Management Proposal

b. Volume II, Cost Proposal – {No Page Limit}

6. Submission Dates and Times

a. Proposal Abstract Date

b. Full Proposal Date

7. Intergovernmental Review

8. Funding Restrictions

V. APPLICATION REVIEW INFORMATION

A. EVALUATION CRITERIA

B. REVIEW AND SELECTION PROCESS

VI. AWARD ADMINISTRATION INFORMATION

A. SELECTION NOTICES

B. ADMINISTRATIVE AND NATIONAL POLICY REQUIREMENTS

1. Meeting and Travel Requirements

2. Human Use

3. Animal Use

4. Publication Approval

5. Export Control

6. Subcontracting

7. Employment Eligibility Verification

8. Central Contractor Registration (CCR) and Universal Identifier Requirements

9. Reporting Executive Compensation and First-Tier Subcontract Awards

10. Updates of Information Regarding Responsibility Matters

11. Representation by Corporations Regarding Unpaid Delinquent Tax Liability or a Felony Conviction Under Any Federal Law

C. REPORTING

D. ELECTRONIC SYSTEMS

1. Representations and Certifications

2. Wide Area Work Flow (WAWF)

3. i-Edison

VII. AGENCY CONTACTS

VIII. OTHER INFORMATION

A. INTELLECTUAL PROPERTY PROCUREMENT CONTRACT PROPOSERS

1. Noncommercial Items (Technical Data and Computer Software)

2. Commercial Items (Technical Data and Computer Software)

B. NON-PROCUREMENT CONTRACT PROPOSERS – NONCOMMERCIAL AND

COMMERCIAL ITEMS (TECHNICAL DATA AND COMPUTER SOFTWARE)

C. ALL PROPOSERS – PATENTS

D. ALL PROPOSERS – INTELLECTUAL PROPERTY REPRESENTATIONS

E. ALL PROPOSERS – TEAMING (OPTIONAL – INCLUDE IF USING A TEAMING WEBSITE)

APPENDIX A

APPENDIX B

Part I: Overview Information

• Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Defense Sciences Office

• Funding Opportunity Title – Butyrylcholinesterase Expression in Plants

• Announcement Type – Initial Announcement

• Funding Opportunity Number – Broad Agency Announcement

DARPA-BAA-12-31

• Catalog of Federal Domestic Assistance Numbers (CFDA) – 12.910

Research and Technology Development

• Dates o Posting Date : Fenruary 16, 2012 o Proposal Abstracts Due March 12, 2012, 4:00 PM ET o Full Proposals Due April 26, 2012, 4:00 PM ET

• Concise description of the funding opportunity – DARPA is seeking innovative research proposals that will demonstrate the ability to produce a recombinant butyrylcholinesterase (rBuChE) using the Nicotiana benthamiana plant-based expression platform that has the same pharmacokinetic profile as a plasma-derived human butyrylcholinesterase (hBuChE) butyrylcholinesterase.

The funding is intended to establish the technical precedence for the use of the plant platform to generate a rapid and scalable form of pre-exposure therapeutic bioscavenger against organophosphate nerve agents. Funding is for basic research only. The anticipated period of funding is for 12 months.

• Anticipated individual awards – Multiple awards are anticipated.

• Types of instruments that may be awarded -- Procurement contract, grant, cooperative agreement or other transaction.

• Any cost sharing requirements – Cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

• Agency contact

Points of Contact:

The BAA Technical POC is Dr. Alan Magill, who can be reached at DARPA-BAA-12-31@darpa.mil.

The BAA Administrator for this effort can be reached at:

E-mail: DARPA-BAA-12-31@darpa.mil

DARPA/DSO

ATTN: DARPA-BAA-12-31

3701 North Fairfax Drive Arlington, VA 22203-1714 mailto:DARPA-BAA-12-31@darpa.mil mailto:DARPA-BAA-11-70@darpa.mil

Solicitations can be viewed at:

http://www.darpa.mil/Opportunities/Solicitations/DSO_Solicitations.aspx Teaming Information (See Section VIII.E.) can be viewed at:

https://team.sainc.com/rBuChE http://www.darpa.mil/Opportunities/Solicitations/DSO_Solicitations.aspx

Part II: Full Text of Announcement

I. FUNDING OPPORTUNITY DESCRIPTION

The Defense Advanced Research Projects Agency often selects its research efforts through the Broad Agency Announcement (BAA) process. The BAA will appear first on the FedBizOpps website, http://www.fedbizopps.gov/, and the Grants.gov website http://www.grants.gov/. The following information is for those wishing to respond to the

BAA.

DARPA is soliciting innovative research proposals in the area of recombinant butyrylcholinesterase (rBuChE) expression in plants, specifically Nicotiana benthamiana.

Proposed research should investigate innovative approaches that enable revolutionary advances in science, technologies, or systems that allow the expression of rBuChE enzyme within these plants; the produced protein must mimic the pharmacokinetics and organophosphorus nerve agent binding characteristics of human plasma-derived butyrylcholinesterase (hBuChE). The development of this capability is expected to result in a drug that can protect the warfighter from chemical threat agent exposures. Proposed research that primarily results in evolutionary improvements to the existing state of practice, or that addresses only plant expression or bioscavenger pharamacokinetic stability (without addressing both components) will be considered non-responsive.

The introduction of a properly stockpiled nerve agent prophylaxis or therapeutic could provide protection to the warfighter and our nation against chemical warfare attacks. A noteworthy scenario exemplifying the potential for catastrophic attack was illustrated by the 1995 Tokyo subway incident in which the terrorist group Aum Shinrikyo used the nerve agent Sarin to kill 13 people and injure 6,000 others. According to a report by the Center for a New American Security, if the Aum Shinrikyo terrorist group had released a more pure form of Sarin, this small scale attack would have had a greater lethality on the population, (see reference 1 below). The potential for Sarin and other organophosphorus nerve agents (OPs) to cause significant mortality underlies the need for effective therapeutic countermeasures. After percutaneous or inhalation exposure, nerve agent enters the peripheral or central nervous system and binds to acetylcholinesterase (AChE), interfering with the acetylcholine signaling. The collective effects of AChE inhibition are clinically recognizable as cholinergic crisis and result in a multitude of symptoms that may lead to death via complete respiratory depression due to excessive muscle contraction of the diaphragm. OPs are among the lethal compound known, with extremely rapid onset of symptoms and toxicity at microgram per kilogram doses.

Currently, there is no effective prophylaxis (pretreatment that does not require a post-exposure treatment) for chemical agent exposure. Atropine and diazepam are available to treat post exposure, but are only effective at <2 x LD50 exposure for some nerve agents.

Pretreatment with pyridostigmine is therapeutically useful for < 5 x LD50 of GD (soman), but is not approved by the Food and Drug Administration (FDA) for use with OPs other than GD (soman). While these conventional treatments increase the chance of survival, they do not prevent the cholinergic crisis and incapacitation brought on by OP poisons.

http://www.fedbizopps.gov/ http://www.grants.gov/

Therefore, without a more capable OP neutralizing therapy, a clear danger exists to the individual warfighter, the force strength and the civilian population.

Bioscavengers have been explored as prophylactic countermeasures to address the gaps identified with the current treatment regime, and are the only chemical prophylactic countermeasure in development. Research indicates that plasma derived human butyrylcholinesterase (hBuChE) can successfully act as a bioscavenger, providing stoichiometric 1:1 levels of protection against nerve agents. This highly glycosylated and sialylated protein is produced within the liver and is found predominantly in the plasma, where it likely circulates as a tetramer. While its biological role is not fully understood, BuChE has been found to detoxify OPs by forming a covalent bond with the agent, thereby neutralizing the OP and inactivating the enzyme, (see reference 2 below).

Because OPs bind BuChE at a 1:1 ratio and are very small relative to the enzyme, large doses of enzyme are necessary to bind and inactivate otherwise lethal amounts of OPs; a single human dose of BuChE is predicted to be ~400mg. However, it should be noted that the extent of protection afforded by BuChE are thought to vary between different OPs.

Butyrylcholinesterase derived from human plasma has been developed for the protection of the warfighter and overall force readiness. In 2006, human plasma-derived butyrylcholinesterase (hBuChE) was registered as an Investigational New Drug by the FDA and in 2009 was used in a Phase I clinical trial, becoming the first bioscavenger protein developed for prophylaxis against OP poisoning (NCT00333528)(2). Plasma-derived BuChE administered intravenously (I.V.) has been shown in animal models to provide protection in less than 10 minutes and is predicted to remain effective for over 10 days in humans. Animal studies demonstrated that hBuChE has the capability to protect against up to 5 x LD50 of various nerve agents, (see references 2, 3 and 4).

Major limitations exist with plasma-derived hBuChE to include the large dose necessary for treatment, an anticipated overall cost per treatment dose of greater than $10,000 for plasma-derived hBuChE, issues with scalability and availability of human plamsa, and complexities associated with IV administration. These limitations necessitate an alternative platform capable of large scale production that is able to dramatically lower the cost/dose while still providing the same protection as plasma-derived BuChE.

Human-like recombinant BuChE has been successfully expressed in alternative recombinant expression platforms, including transgenic goats, plants, insect cells, and cultured mammalian cells, (see references 4, 5 and 6). However, due to the short half-life in circulation in the blood stream, challenges with furthering development exist which creates a potential operational problem of repeated dosing. The plasma derived hBuChE circulatory life of 10 days in humans has not been achieved by other recombinant forms.

It is thought that this may be explained by the recombinant proteins lacking either the capability to produce tetrameric forms and/or the ability to be properly glycosylated and sialylated. These characteristics, however, do not appear to impact the enzymatic activity or OP binding capacity. Recent advances in protein chemistry with respect to tetramerization, sialylation, PEGylation and other stabilization strategies suggest that a more stable rBuChE product can be produced either with in situ modification of the enzyme during expression or via product modification after purification of the enzyme.

However, a platform system that is capable of both rapid and large scale production of this enzyme with the required pharmacokinetic stability still needs to be developed.

The advancement of plant based manufacturing platforms for the expression of recombinant proteins through programs such as the DARPA H1N1 Acceleration Program may provide the appropriate production platform for a future rBuChE stockpile. The Nicotiana benthamiana platform’s unique advantages of enhanced biosafety (lack of adventitious viruses), ease of scaling, flexibility in protein expression, and reduced cost of production make it especially attractive for the production of medical countermeasures. Previous work with plant derived BuChE has shown that it is similar to human plasma-derived BuChE in terms of catalytic activity, inhibitor binding and protection against OP challenge in animals, but that the circulatory stability (half-life) was dramatically lower than that of plasma- derived hBuChE, (see reference 5 below).

The Butyrylcholinesterase Expression in Plants Program is seeking technological advancements that are capable of bridging the large scale plant expression technology for the production of rBuChE with improved pharmacokinetic properties that mimic plasma derived hBuChE.

DARPA is seeking approaches for development of recombinant human butyrylcholinesterase bioscavenger as a prophylactic countermeasure against OPs.

Proteins must be produced within the plant platform Nicotiana benthamiana and must mimic the enzyme kinetic properties and in vivo pharmacokinetic profile of plasma-derived hBuChE when injected intramuscularly (I.M.) or intravenously (I.V.) into guinea pigs. Alternative routes of administration may be considered as long as the enzyme can be formulated and tested for I.M. and I.V. injection. Engineered forms of rBuChE may be considered, though a high level of homology to the parent human amino acid sequence is preferred. DARPA is not interested in expression of other bioscavengers, including those with catalytic activity for the purposes of this BAA, and would consider these approaches non-responsive. Strategies may include manipulation of protein expression machinery within the plant or protein modifications and/or formulations post production.

Due to expected time and capacity constraints regarding in vivo testing, the methodology and rationale for down selection of potential bioscavenger candidates in vitro should be clearly stated. Proposers must ensure that all methods and demonstrations of capability are compliant with institutional and governmental regulation and are not in violation of the Biological Weapons Convention (http://www.state.gov/www/global/arms/treaties/bwc1.html). The methodology for assessing enzyme activity can be found at the Teaming and Information Website referenced in Part I. Candidate bioscavenger products produced in this program will be delivered by the performer, at the end of the period of performance, to a DARPA designated site to test efficacy and pharmacokinetic stability. There is no requirement for the successful proposal(s) to test candidate products against nerve agents, OPs, or simulants in vitro or in vivo.

http://www.state.gov/www/global/arms/treaties/bwc1.html

Each performer will be responsible for meeting the following Metrics and Milestones during the course of the program, which is anticipated to be a 12 month period of performance:

1. Production of ≥1g of rBuChE from Nicotiana benthamiana that meets the requirements outlined below:

a. Confirmation of amino acid sequence of rBuChE by appropriate method(s). If alterations to the nucleic acid or amino acid sequences were engineered, report the variances and sequence homology compared to the parent human BuChE sequence (NCBI Accession number: NM_000055).

b. Demonstration by appropriate methodology of >95% purity (with respect to other proteins) with low levels of other contaminants such as detergents, preservatives or other compounds incompatible with in vivo use.

c. Perform biophysical characterization assays appropriate for candidate bioscavenger molecules. For example, oligomerization and the status of post-translational modifications present on hBuChE (e.g., glycosylation, sialylation) are thought to be important parameters for plasma derived hBuChE.

d. Formulation and storage conditions are at the performers’ discretion, but product should be stable in storage at 4oC for Government testing.

Demonstrate integrity of product after storage at 4oC for up to six months or the end of the period of performance for this project.

2. Demonstrate enzyme activity as functionally equivalent to that of plasma-derived BuChE.

a. The in vitro enzyme kinetics of the rBuChE enzyme should display ≥400 U/mg activity with butyrylthiocholine as a substrate (Recommended assay methodology and a definition for enzyme units can be found at the Teaming and Information Website referenced in Part I).

3. Provide pharmacokinetic (PK) profile of rBuChE after both intramuscular (I.M.) and intravenous (I.V.) administration that is, at a minimum, equivalent to that of human plasma-derived BuChE (Please refer to the Teaming and Information Website referenced in Part I for PK graph).

a. Preferred animal model is male Hartley guinea pigs, to be injected in the rear thigh with rBuChE; BuChE activity levels in the blood or plasma can be measured with assay described in paragraph 2a above.

b. Derive PK parameters such as elimination half-time (T1/2), maximal concentration (Cmax), time to maximal concentration (Tmax), and mean retention time (MRT); target is to meet or exceed a T1/2 of 72 hours, with a linear relationship between administered dose of rBuChE and Cmax.

4. Deliver purified rBuChE protein (1 gram) to a DARPA designated site for chemical agent testing (in vitro enzyme kinetics, pharmacokinetics studies and efficacy testing in guinea pigs using bona fide organophosphorus nerve agents).

5. Provide an estimated cost of goods at various scales of production and expected scalability limitations, if any. The bioscavenger program is targeting a 100 fold decrease in cost/ 400mg dose, for a cost equivalent of ~$200 per treatment.

The long term goal, albeit outside the scope of this solicitation, of developing an FDA approved chemical countermeasure should be considered. Government partner agencies are pursuing bioscavenger for advanced development and may have specific acquisition goals for transition and further development of any successful rBuChE technology. This includes reduced costs/dose, ease of administration and delivery, specific objectives for enzyme formulation for bioavailability, pharmacokinetics and shelf-life stability.

Therefore, it is in the proposer’s interest to consider appropriate technological compatibility with these requirements and intellectual property freedom to operate for further government development of this medical countermeasure.

References:

1. Danzig et al., Aum Shinrikyo Insights Into How Terrorists Develop Biological and Chemical Weapons. http://www.cnas.org/aumshinrikyo

2. Masson and Lockridge, Arch Biochem Biophys. 2010 Feb 15;494(2):107-20.

3. Saxena et al., Biochem Pharmacol. 2011 Jan 1;81(1):164-9.

4. Lenz et al., Toxicology. 2007 Apr 20;233(1-3):31-9.

5. Geyer et al., Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20251-6.

6. Huang et al., Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13603-8.

II. AWARD INFORMATION

Multiple awards are anticipated. The amount of resources made available under this BAA will depend on the quality of the proposals received and the availability of funds.

The Government reserves the right to select for negotiation all, some, one, or none of the proposals received in response to this solicitation, and to make awards without discussions with proposers. The Government also reserves the right to conduct discussions if it is later determined to be necessary. If warranted, portions of resulting awards may be segregated into pre-priced options. Additionally, DARPA reserves the right to accept proposals in their entirety or to select only portions of proposals for award.

In the event that DARPA desires to award only portions of a proposal, negotiations may be opened with that proposer. The Government reserves the right to fund proposals in periods with options for continued work at the end of one or more of the periods.

Awards under this BAA will be made to proposers on the basis of the evaluation criteria listed below (see section labeled “Application Review Information”, Sec. V.), and program balance to provide overall value to the Government. Proposals identified for negotiation may result in a procurement contract, grant, cooperative agreement, or other transaction depending upon the nature of the work proposed, the required degree of http://www.cnas.org/aumshinrikyo http://www.ncbi.nlm.nih.gov/pubmed/20004171 http://www.ncbi.nlm.nih.gov/pubmed/20846507 http://www.ncbi.nlm.nih.gov/pubmed/17188793 http://www.ncbi.nlm.nih.gov/pubmed/21059932 http://www.ncbi.nlm.nih.gov/pubmed/17660298 interaction between parties, and other factors. The Government reserves the right to request any additional, necessary documentation once it makes the award instrument determination. Such additional information may include but is not limited to Representations and Certifications. The Government reserves the right to remove proposers from award consideration should the parties fail to reach agreement on award terms, conditions and cost/price within a reasonable time or the proposer fails to timely provide requested additional information.

As of the date of publication of this BAA, DARPA expects that program goals for this BAA may be met by proposers intending to perform 'fundamental research,' i.e., basic or applied research performed on campus in science and engineering, the results of which ordinarily are published and shared broadly within the scientific community, as distinguished from proprietary research and from industrial development, design, production, and product utilization the results of which ordinarily are restricted for proprietary or national security reasons. Notwithstanding this statement of expectation, DARPA is not prohibited from considering and selecting research proposals that, while perhaps not qualifying as 'fundamental research' under the foregoing definition, still meet the BAA criteria for submissions. If proposals are selected for award that offer other than a fundamental research solution, then DARPA will either work with the proposer to modify the proposed statement of work to bring the research back into line with fundamental research or else the proposer will agree to restrictions in order to receive an award. See Section VI.B.4 for further information on fundamental, non-fundamental and restricted research. In all cases, the DARPA contracting officer shall have sole discretion to select award instrument type and to negotiate all instrument provisions with selectees.

III. ELIGIBILITY INFORMATION

A. Eligible Applicants

All responsible sources capable of satisfying the Government's needs may submit a proposal that shall be considered by DARPA. Historically Black Colleges and Universities (HBCUs), Small Businesses, Small Disadvantaged Businesses and Minority Institutions (MIs) are encouraged to submit proposals and join others in submitting proposals; however, no portion of this announcement will be set aside for these organizations’ participation due to the impracticality of reserving discrete or severable areas of this research for exclusive competition among these entities.

Federally Funded Research and Development Centers (FFRDCs) and Government entities (Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they address the following conditions. FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector AND must also provide a letter on letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to government solicitations and compete with industry, and compliance with the associated FFRDC sponsor agreement and terms and conditions. This information is required for FFRDCs proposing to be prime or subcontractors. Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority (as well as, where relevant, contractual authority) establishing their ability to propose to Government solicitations.

At the present time, DARPA does not consider 15 U.S.C. § 3710a to be sufficient legal authority to show eligibility. While 10 U.S.C. § 2539b may be the appropriate statutory starting point for some entities, specific supporting regulatory guidance, together with evidence of agency approval, will still be required to fully establish eligibility. DARPA will consider eligibility submissions on a case-by-case basis; however, the burden to prove eligibility for all team members rests solely with the Proposer.

B. Procurement Integrity, Standards of Conduct, Ethical Considerations, and

Organizational Conflicts of Interest

Current federal employees are prohibited from participating in particular matters involving conflicting financial, employment, and representational interests (18 U.S.C. §§ 203, 205, and 208). The DARPA Program Manager for this BAA is Dr. Alan Magill.

Once the proposals have been received, and prior to the start of proposal evaluations, the Government will assess potential conflicts of interest and will promptly notify the Proposer if any appear to exist. (Please note, the Government assessment does NOT affect, offset, or mitigate the Proposer’s own duty to give full notice and planned mitigation for all potential organizational conflicts, as discussed below.)

Without prior approval or a waiver from the DARPA Director, in accordance with FAR 9.503, a Contractor cannot simultaneously provide scientific, engineering, technical assistance (SETA) or similar support and also be a technical performer. Therefore, all Proposers as well as proposed subcontractors and consultants must affirm whether they (their organizations and individual team members) are providing SETA or similar support to any DARPA technical office(s) through an active contract or subcontract. All affirmations must state which office(s) the Proposer, subcontractor, consultant, or individual supports and identify the prime contract number(s). Affirmations shall be furnished at the time of proposal submission. All facts relevant to the existence or potential existence of organizational conflicts of interest (FAR 9.5) must be disclosed.

The disclosure must include a description of the action the Proposer has taken or proposes to take to avoid, neutralize, or mitigate such conflict. If in the sole opinion of the Government after full consideration of the circumstances, a proposal fails to fully disclose potential conflicts of interest and/or any identified conflict situation cannot be effectively mitigated, the proposal will be rejected without technical evaluation and withdrawn from further consideration for award.

If a prospective Proposer believes that any conflict of interest exists or may exist (whether organizational or otherwise) or has questions on what constitutes a conflict of interest, the Proposer should promptly raise the issue with DARPA by sending his/her contact information and a summary of the potential conflict to the BAA mailbox before time and effort are expended in preparing a proposal and mitigation plan.

C. Cost Sharing/Matching

Cost sharing is not required for this particular program; however, cost sharing will be carefully considered where there is an applicable statutory condition relating to the selected funding instrument (e.g., for any Other Transactions under the authority of 10 U.S.C. § 2371). Cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

D. Other Eligibility Criteria

Collaborative Efforts

Collaborative efforts/teaming are encouraged. A teaming website, https://team.sainc.com/rBuChE, will facilitate the formation of teams with the necessary expertise. Specific content, communications, networking, and team formation are the sole responsibility of the participants. Neither DARPA nor the Department of Defense (DoD) endorses the destination website of the information and organizations contained therein, nor does DARPA or the DoD exercise any responsibility at the destination. This website is provided consistent with the stated purpose of this BAA.

IV. APPLICATION AND SUBMISSION INFORMATION

A. Address to Request Application Package

This solicitation contains all information required to submit a proposal. No additional forms, kits, or other materials are needed. This notice constitutes the total BAA. No additional information is available, nor will a formal Request for Proposal (RFP) or additional solicitation regarding this announcement be issued. Requests for same will be disregarded.

B. Content and Form of Application Submission

1. Security and Proprietary Issues

NOTE: If proposals are classified, the proposals must indicate the classification level of not only the proposal itself, but also the anticipated award document classification level.

The Government anticipates proposals submitted under this BAA will be unclassified.

However, if a proposal is submitted as “Classified National Security Information” as defined by Executive Order 13526, then the information must be marked and protected as though classified at the appropriate classification level and then submitted to DARPA for a final classification determination.

Security classification guidance via a DD Form 254, “DoD Contract Security Classification Specification,” will not be provided at this time, since DARPA is soliciting ideas only. After reviewing the incoming proposals, if a determination is made that the award instrument may result in access to classified information, a DD Form 254 will be issued and attached as part of the award.

Proposers choosing to submit a classified proposal from other classified sources must first receive permission from the respective Original Classification Authority in order to use their information in replying to this BAA. Applicable classification guide(s) should also be submitted to ensure the proposal is protected at the appropriate classification level.

Classified submissions shall be appropriately and conspicuously marked with the proposed classification level and declassification date. Submissions requiring DARPA to make a final classification determination shall be marked as follows:

CLASSIFICATION DETERMINATION PENDING. Protect as though classified (insert the recommended classification level: (e.g., Top Secret, Secret or Confidential)

Classified submissions shall be in accordance with the following guidance:

Confidential and Secret Collateral Information: Use classification and marking guidance provided by previously issued security classification guides, the Information Security Regulation (DoD 5200.1-R), and the National Industrial Security Program Operating Manual (DoD 5220.22-M) when marking and transmitting information previously classified by another Original Classification Authority. Classified information at the Confidential and Secret level may be submitted via ONE of the two following methods:

1. Hand-carried by an appropriately cleared and authorized courier to the DARPA CDR. Prior to traveling, the courier shall contact the DARPA CDR at 703-526-4052 to coordinate arrival and delivery.

OR

2. Mailed via appropriate U.S. Postal Service methods (USPS) (e.g., USPS Registered Mail or USPS Express Mail). All classified information will be enclosed in opaque inner and outer covers and double wrapped. The inner envelope shall be sealed and plainly marked with the assigned classification and addresses of both sender and addressee.

The inner envelope shall be addressed to:

Defense Advanced Research Projects Agency ATTN: Defense Sciences Office Reference: DARPA-BAA-12-31

The outer envelope shall be sealed with no identification as to the classification of its contents and addressed to:

Defense Advanced Research Projects Agency Security & Intelligence Directorate, Attn: CDR

All Top Secret materials: Top Secret information should be hand carried by an appropriately cleared and authorized courier to the DARPA CDR. Prior to traveling, the courier shall contact the DARPA CDR at 703-526-4052 to coordinate arrival and delivery.

Special Access Program (SAP) Information: SAP information must be transmitted via approved methods. Prior to transmitting SAP information, contact the DARPA SAPCO at 703-526-4052 for instructions.

Sensitive Compartmented Information (SCI): SCI must be transmitted via approved methods. Prior to transmitting SCI, contact the DARPA Special Security Office (SSO) at 703-526-4052 for instructions.

Proprietary Data: All proposals containing proprietary data should have the cover page and each page containing proprietary data clearly marked as containing proprietary data. It is the Proposer’s responsibility to clearly define to the Government what is considered proprietary data.

Proposers must have existing and in-place prior to execution of an award, approved capabilities (personnel and facilities) to perform research and development at the classification level they propose. It is the policy of DARPA to treat all proposals as competitive information, and to disclose their contents only for the purpose of evaluation. Proposals will not be returned. The original of each proposal received will be retained at DARPA and all other non-required copies destroyed. A certification of destruction may be requested, provided the formal request is received at this office within 5 days after unsuccessful notification.

2. Abstract Submission Information

Proposers who choose to use abstracts are strongly encouraged to submit an abstract in advance of a full proposal. This procedure is intended to minimize unnecessary effort in proposal preparation and review. The time and date for submission of abstracts is specified in Section C below. DARPA will acknowledge receipt of the submission and assign a control number that should be used in all further correspondence regarding the abstract.

DARPA will respond to abstracts with a statement as to whether DARPA is interested in the idea. DARPA will attempt to reply to abstracts via e-mail within thirty (30) calendar days of receipt. Should a proposer be discouraged from submitting a full proposal, the letter must contain feedback for the proposer regarding the rationale for the decision not to recommend a full proposal be submitted. Abstracts will be reviewed in the order they are received. Early submissions of abstracts and full proposals are strongly encouraged because selections may be made at any time during the period of solicitation. Regardless of DARPA’s response to an abstract, proposers may submit a full proposal. DARPA will review all full proposals submitted using the published evaluation criteria and without regard to any comments resulting from the review of an abstract.

For Abstracts Being Submitted as Hard Copies/On CD-ROM:

Proposers must submit an original hardcopy and one (1) electronic copy of the proposal abstract in PDF (preferred) on a CD-ROM to the mailing address listed in Part I. Each copy must be clearly labeled with DARPA-BAA-12-31, proposer organization, technical point of contact, and proposal title (short title recommended).

For Proposers Posting Abstracts to Grants.Gov:

If proposers intend to use Grants.gov as their means of submission, then they must submit their entire proposal abstract through Grants.gov; applications cannot be submitted in part to Grants.gov and in part as a hard-copy. Proposers using Grants.gov do not submit hardcopy proposal abstracts in addition to the Grants.gov electronic submission.

Proposers must complete the following steps in the order listed below before submitting proposal abstracts on Grants.gov (these steps are also detailed at http://www.grants.gov/applicants/get_registered.jsp):

• Proposers must obtain a DUNS number.

• Proposers must register their organization in the Central Contractor Registration

(CCR) https://www.bpn.gov/ccr/default.aspx).

• Proposers must register the Authorized Organization Representative (AOR) in

Grants.gov.

• Proposers must have the organization’s E-BIZ point of contact authorize the AOR to submit applications.

Once Grants.gov has received a proposal abstract submission, Grants.gov will send two e-mail messages to advise proposers as to whether or not their proposal abstracts have been validated or rejected by the system; IT MAY TAKE UP TO TWO DAYS TO RECEIVE THESE E-MAILS. The first e-mail will confirm receipt of the proposal abstract by the Grants.gov system; this e-mail only confirms receipt, not acceptance, of the proposal abstract. The second will indicate that the application has been successfully validated by the system prior to transmission to the grantor agency or has been rejected due to errors. If the proposal abstract is validated, then the proposer has successfully submitted their proposal abstract. If the proposal abstract is rejected, the proposer will have to resubmit their proposal abstract. Once the proposal abstract is retrieved by DARPA, the proposer will receive a third e-mail from Grants.gov. To avoid missing deadlines, proposers should submit their proposal abstract in advance of the due date with http://www.grants.gov/applicants/get_registered.jsp https://www.bpn.gov/ccr/default.aspx sufficient time to receive confirmations and correct any errors in the submission process through Grants.gov. For more information on submitting proposal abstract to Grants.gov, visit the Grants.gov submissions page at:

http://grants.gov/applicants/apply_for_grants.jsp.

Proposers electing to submit grant or cooperative agreement proposal abstracts as hard copies must complete the SF 424 R&R form (Application for Federal Assistance, Research and Related) available on the Grants.gov website http://www.grants.gov/agencies/aapproved_standard_forms.jsp#2.

Technical support for Grants.gov submissions may be reached at 1-800-518-4726 or support@grants.gov.

Please note that due to the new DARPA security policies, submitters to grants.gov will still need to visit https://dsobaa.sainc.com to register their organization concurrently and are also required to send in a password form via e-mail to the address listed in Part I ensure the DSO BAA office can verify the security of their submission.

For Proposers Submitting to an Electronic Business Application (Not Submitting Hard Copies/CD-ROM):

Proposal abstracts sent in response to DARPA-BAA-12-31 may be submitted via DSO’s BAA Website (https://dsobaa.sainc.com). Visit the website to register for an account (via the “Register your Organization” link along the left side of the homepage), view submission instructions, and upload/finalize the proposal abstract. All submissions must be compressed and encrypted as described below. Proposers using the DSO BAA Website may encounter heavy traffic on the submission deadline date; it is highly advised that submission process be started as early as possible.

All proposal abstracts submitted electronically by means of an Electronic Business Application Tool or proposal submission web site (not including Grants.gov) must be encrypted using WinZip or PKZip with 256-bit AES encryption. Only one zipped/encrypted file will be accepted per proposal abstract and proposal abstracts not zipped/encrypted will be rejected by DARPA. An encryption password form must be completed and e-mailed to DARPA-BAA-12-31@darpa.mil at the time of proposal submission. See https://dsobaa.sainc.com for the encryption password form.

Note the word “PASSWORD” must appear in the subject line of the above e-mail and there are minimum security requirements for establishing the encryption password.

Failure to provide the encryption password may result in the proposal not being evaluated. For further information and instructions on how to zip and encrypt proposal abstract files, see https://dsobaa.sainc.com.

Upon review, DARPA will provide written feedback on the likelihood of a full proposal being selected and the time and date for submission of a full proposal, which may differ from the originally published date below.

http://grants.gov/applicants/apply_for_grants.jsp http://www.grants.gov/agencies/aapproved_standard_forms.jsp#2.

mailto:support@grants.gov https://dsobaa.sainc.com/ https://dsobaa.sainc.com/ mailto:DARPA-BAA-https://dsobaa.sainc.com/

3. Proposal Submission Information

Proposers are required to submit proposals by the time and date specified in the BAA in order to be considered for selection. DARPA may evaluate proposals received after this date for a period up to one year from date of posting on FedBizOpps and Grants.gov.

Ability to review late submissions remains contingent on availability of funds.

The typical proposal should express a consolidated effort in support of one or more related technical concepts or ideas. Disjointed efforts should not be included into a single proposal.

Restrictive notices notwithstanding, proposals may be handled, for administrative purposes only, by a support contractor. This support contractor is prohibited from competition in DARPA technical research and is bound by appropriate nondisclosure requirements. Proposals and abstracts may not be submitted by fax or e-mail; any so sent will be disregarded.

Proposals not meeting the format described in the BAA may not be reviewed.

For Proposers Submitting Full Proposals, as Hard Copies/ On CD-ROM:

Proposers must submit an original hardcopy, one (1) electronic copy of the full proposal [in PDF (preferred)] on a CD-ROM to the mailing address listed in Part I. Each copy must be clearly labeled with DARPA-BAA-12-31, proposer organization, proposal title (short title recommended).

For Proposers Posting to Grants.Gov:

Grant or cooperative agreement proposals may only be submitted to DARPA through Grants.gov or in hard-copy. Grant or cooperative agreement proposals may not be submitted through any other means (including https://dsobaa.sainc.com and other comparable systems). If proposers intend to use Grants.gov as their means of submission, then they must submit their entire proposal through Grants.gov; applications cannot be submitted in part to Grants.gov and in part as a hard-copy. Proposers using Grants.gov do not submit hardcopy proposals in addition to Grants.gov electronic submission.

Proposers must complete the following steps in the order listed below before submitting proposals on Grants.gov (these steps are also detailed at http://www.grants.gov/applicants/get_registered.jsp):

• Proposers must obtain a DUNS number.

• Proposers must register their organization in the Central Contractor Registration

(CCR) https://www.bpn.gov/ccr/default.aspx).

• Proposers must register the Authorized Organization Representative (AOR) in

Grants.gov.

https://dsobaa.sainc.com/ http://www.grants.gov/applicants/get_registered.jsp https://www.bpn.gov/ccr/default.aspx

• Proposers must have the organization’s E-BIZ point of contact authorize the AOR to submit applications.

Once Grants.gov has received a proposal submission, Grants.gov will send two e-mail messages to advise proposers as to whether or not their proposals have been validated or rejected by the system; IT MAY TAKE UP TO TWO DAYS TO RECEIVE THESE E- MAILS. The first e-mail will confirm receipt of the proposal by the Grants.gov system;

this e-mail only confirms receipt, not acceptance, of the proposal. The second will indicate that the application has been successfully validated by the system prior to transmission to the grantor agency or has been rejected due to errors. If the proposal is validated, then the proposer has successfully submitted their proposal. If the proposal is rejected, the proposer will have to resubmit their proposal. Once the proposal is retrieved by DARPA, the proposer will receive a third e-mail from Grants.gov. To avoid missing deadlines, proposers should submit their proposals in advance of the final proposal due date with sufficient time to receive confirmations and correct any errors in the submission process through Grants.gov. For more information on submitting proposals to Grants.gov, visit the Grants.gov submissions page at:

http://grants.gov/applicants/apply_for_grants.jsp.

Upload two separate documents, Volume I, Technical and Management Proposal, and Volume II, the Cost Proposal, as attachments to the application package. No other Grants.gov forms are required. Please note that Grants.gov does not accept zipped or encrypted proposals. More detailed instructions for using Grants.gov can be found on the Grants.gov website.

Proposers electing to submit grant or cooperative agreement proposals as hard copies must complete the SF 424 R&R form (Application for Federal Assistance, Research and Related) available on the Grants.gov website http://www.grants.gov/agencies/aapproved_standard_forms.jsp#2.

Technical support for Grants.gov submissions may be reached at 1-800-518-4726 or support@grants.gov.

Please note that due to the new DARPA security policies, submitters to grants.gov will still need to visit https://dsobaa.sainc.com to register their organization concurrently and are also required to send in a password form via e-mail to the address listed in Part I to ensure the DSO BAA office can verify the security of their submission.

For Proposers Submitting to an Electronic Business Application (Not Submitting Hard Copies/CD-ROM):

Full proposals sent in response to DARPA-BAA-12-31 may be submitted via DSO’s BAA Website (https://dsobaa.sainc.com). Visit the website to register for an account (via the “Register your Organization” link along the left side of the homepage), view submission instructions, and upload/finalize the proposal. All submissions must be compressed and encrypted as described below. Proposers using the DSO BAA Website http://grants.gov/applicants/apply_for_grants.jsp http://www.grants.gov/agencies/aapproved_standard_forms.jsp#2.

mailto:support@grants.gov may encounter heavy traffic on the submission deadline date; it is highly advised that submission process be started as early as possible.

All proposals submitted electronically by means of an Electronic Business Application Tool or proposal submission web site (not including Grants.gov) must be encrypted using WinZip or PKZip with 256-bit AES encryption. Only one zipped/encrypted file (containing both proposal volumes) will be accepted per proposal and proposals not zipped/encrypted will be rejected by DARPA. An encryption password form must be completed and e-mailed to DARPA-BAA-12-31@darpa.mil at the time of proposal submission. See https://dsobaa.sainc.com for the encryption password form.

Note the word “PASSWORD” must appear in the subject line of the above e-mail and there are minimum security requirements for establishing the encryption password.

Failure to provide the encryption password may result in the proposal not being evaluated. For further information and instructions on how to zip and encrypt proposal files, see https://dsobaa.sainc.com.

For All:

All administrative correspondence and questions on this solicitation, including requests for information on how to submit an abstract or full proposal to this BAA, should be directed to one of the administrative addresses below (e-mail is preferred).

BAA Administrator E-mail: DARPA-BAA-12-31@darpa.mil

DARPA/DSO

ATTN: DARPA-BAA-12-31

DARPA intends to use electronic mail for correspondence regarding DARPA-BAA-12-

31. Proposals may not be submitted by fax or e-mail; any so sent will be disregarded.

DARPA encourages use of the Internet for retrieving the BAA and any other related information that may subsequently be provided.

4. Abstract Format

Abstracts are encouraged in advance of full proposals in order to provide potential proposers with a rapid response to minimize unnecessary effort. Abstracts should follow the same general format as described for Volume I under PROPOSAL FORMAT (see below), but include ONLY Sections I and II. (However, no formal transmittal letter is required.) The cover sheet should be clearly marked “ABSTRACT” and the total length should not exceed 5 pages, excluding cover page. All pages shall be printed on 8-1/2 by 11 inch paper with type not smaller than 12 point. Smaller font may be used for figures, mailto:DARPA-BAA-https://dsobaa.sainc.com/ https://dsobaa.sainc.com/ mailto:DARPA-BAA-tables and charts. The page limitation for abstracts includes all figures, tables, and charts.

No formal transmittal letter is required. All abstracts must be written in English.

5. Full Proposal Format

All full proposals must be in the format given below. Nonconforming proposals may be rejected without review. Proposals shall consist of two volumes. All pages shall be printed on 8-1/2 by 11 inch paper with type not smaller than 12 point. Smaller font may be used for figures, tables and charts. The page limitation for full proposals includes all figures, tables, and charts. Volume I, Technical and Management Proposal, may include an attached bibliography of relevant technical papers or research notes (published and unpublished) which document the technical ideas and approach upon which the proposal is based. Copies of not more than three (3) relevant papers can be included with the submission. The bibliography and attached papers are not included in the page counts given below. The submission of other supporting materials along with the proposals is strongly discouraged and will not be considered for review. Volume I, Technical and Management Proposal, shall not exceed 25 pages. Maximum page lengths for each section are shown in braces { } below. All full proposals must be written in English.

a. Volume I, Technical and Management Proposal

Section I. Administrative

A. Cover sheet to include:

(1) BAA number;

(2) Technical area;

(3) Lead Organization Submitting proposal;

(4) Type of business, selected among the following categories: “LARGE

BUSINESS”, “SMALL DISADVANTAGED BUSINESS”, “OTHER SMALL

BUSINESS”, “HBCU”, “MI”, “EDUCATIONAL”, “NON PROFIT” OR “NOT-

FOR-PROFIT”;

(5) Contractor’s reference number (if any);

(6) Other team members (if applicable) and type of business for each;

(7) Proposal…